00:24:08.17 turned on in another cell. Your email address will not be published. 00:07:32.21 dermal cells in order for them to grow and be maintained. 00:20:44.11 What are the microRNAs that are drivers of squamous cell carcinoma? 00:26:17.28 using fluorescence activated cell sorting to purify those cells, 00:03:45.22 and he could passage them endlessly under conditions where the cells could still make tissue. 00:47:47.26 And here are some examples. 00:19:02.26 then, the stem cells are basically activated. 00:20:10.13 And so, what were the next steps that scientists came up with to generate stem cells that would 00:37:29.05 of an adult skin cell, and turn it into an induced pluripotent stem cell, by the activity 00:18:51.19 to find the pups, and then use a microinjection needle to be able to inject high-titer lentivirus 00:10:52.00 And so we did that experiment. The tumor microenvironment may include immune cells and greater proximity to TGF-beta secreting blood vessels. 00:43:19.21 And it turns out that we can take advantage of that. 00:38:33.24 If we switch them off, we can favor hair follicle tissue regeneration and hair regeneration. 00:28:40.02 induced pluripotent stem cells. 00:11:11.19 and resistant to chemotherapy. 00:15:07.28 into spinal cord neurons. 00:40:53.15 induced pluripotent stem cell-derived beta islet cells not only could survive, but basically also 00:17:00.03 But they're defined in their task and also their program of gene expression 00:17:24.17 And ultimately, we'd like to know which ones are cancer-driving and which ones aren't. 00:37:17.14 Remarkably, now... it's now possible to be able to study these peripheral sensory neurons, 00:18:21.09 very first cell layer that it sees, which, right after gastrulation, is the single layer 00:43:49.24 a promoter region, an enhancer region, and using that to drive expression in mice. A new, innovative anti-aging skincare ingredient that restores your skin's youthful complexion. 00:16:33.24 And even later after the graft. 00:27:27.20 to make a hair follicle, what we found to maintain the hair follicles stem cells... what we found 00:32:41.21 Could he reduce the length of time that stem cells spend in quiescence? Lay K, Kume T, Fuchs E. (2016)  FOXC1 maintains the hair follicle stem cell niche and governs stem cell quiescence to preserve long-term tissue-regenerating potential. 00:37:43.08 And that was a remarkable change and a remarkable advance because it allowed us, now, 00:12:30.11 Scientists are excited about the ability to generate nerve cells for the treatment of 00:25:01.15 genes within a nucleus to... to be able to do something else, to turn on some genes and 2015 Feb 26;160(5):963-976. 00:00:36.19 And yet it's those mechanisms that cancers hijack in order to take advantage of... 00:42:08.04 for every stem cell type. 00:17:21.19 Why is there so much controversy about embryonic stem cell research? 00:43:11.15 is going to lead to new and improved therapies in the future. The correctly modified cells can be selected, grown and multiplied in the lab, then transplanted back onto the patient. 00:26:55.05 without the use of the oocyte cytoplasm, or without the use of the unfertilized egg. 00:28:19.00 In this case, they used retroviruses that harbored the genes encoding KLF4, Oct4, Sox2, 00:20:55.00 by John Gurdon, who recently won the Nobel Prize for these pioneering studies. 00:42:36.05 Well, there's lots of work to be done. 00:22:47.18 And now, if we go to those hybrid cells, effectively, and culture them to the level of the blastocyst, 00:02:16.18 But that was just a postulate. 00:00:31.13 their promise for regenerative medicine. 00:21:29.17 in order to take a skin stem cell, and basically used nuclear transfer in order to put that into 00:21:44.12 The work that we do is focused on mouse. 00:39:47.07 So, what about stem cell therapy for type I diabetes. 00:15:51.25 So, we can also see gamma-H2AX, a sign of DNA damage. 00:16:05.21 But if a stem cell needs to make tissue, now there have to be interacting cues that are 00:37:29.08 allow them to see how pain might be received, and how it might be generated, how it might TGF-β promotes heterogeneity and drug resistance in squamous cell carcinoma. 00:31:54.04 And that's what gives our hair its color. 00:16:57.28 again with cisplatin to wipe out the mobilized, activated cancer stem cells. 00:46:37.20 when the skin sees inflammation again. 00:43:52.15 So, these are advances for the future. 00:07:28.23 that Howard Green had performed, in this case, to culture cornea or corneal epithelial cells 00:19:55.05 but also to produce the shaft that then grows downward, pushing the signaling center 00:21:54.14 So, when taken from their niche and cultured, the green stem cells that you see here, 00:38:35.16 involving iPS cell technology. 00:09:47.08 several different tissues of our body. 00:05:37.27 In those early days, Dr. Green was able to effectively cure or treat patients Our skin has to be constantly renewed throughout our lives. 00:05:30.09 that allowed the cells to grow fast, generate sheets of skin, in order to be able to be used 00:48:00.22 Now, there's inflammation, the skin experiences inflammation, and we see two epigenetic marks 00:18:55.17 And so, again, this issue is, well, the embryos could be implanted into a woman who However, our body has many different types of skin; just compare the palms of your hand to your scalp. 00:36:05.13 And so we began to study this process. 00:13:27.15 suggesting that this is an important finding that could help us in terms of future treatments of cancer. 00:26:34.19 the transcription factors from the skin of the animal. Skin is a very important tissue in our bodies. 00:31:20.12 and the other X chromosome turns out to be silenced. 00:16:19.26 that have high levels of glutathione to be able to kill those cells in the presence of, perhaps, 00:06:31.01 or of cancer, that might give us an idea or a notion that culturing those cells long-term 00:32:33.28 in terms of what induced pluripotent stem cells could do. 00:08:24.11 Stem cells have the ability to make and replenish a tissue, if we're talking about adult stem cells. 00:22:05.07 And that is to work together to be able to advance our knowledge of biology and, ultimately, Clinical applications of epidermal stem cells. 00:45:42.01 the expression of, in this case, a reporter GFP gene. These results suggest that drugs which block TGF-beta activity, in combination with other chemotherapeutics, may be an effective therapy for some SCC. 00:09:42.13 And so we think that it's these cells that are then the ones that get into the bloodstream 00:04:49.27 But effectively, these were tissue stem cells. 00:27:01.18 So, the technology that Yamanaka did, and his coworkers, was to take an adult skin cell 00:07:57.00 of corneal epithelial cells, it was possible, then, to graft it onto the blind eye. 00:15:46.04 that make that decision. 00:14:50.21 and differentiated them into neurons, and used them to treat paralysis of a rat, 448(7151):313-7. 00:15:15.13 Now, these were early studies. Skin stem cells make all this possible. 00:41:03.13 the Nfatc1 gene, and DNA... the BMP downstream gene... transcription factor activators. 00:40:12.20 And they all bind to relatively short stretches of DNA that are contained within these large 00:42:51.20 Diabetes. 00:08:45.15 as junctional epidermolysis bullosa. 00:01:10.04 but also head and neck, cervix, esophagus, cancers of the anal-genital tract, and some types of lung, 00:04:02.28 One of the interesting new sets of genes that are important in the squamous cell carcinoma 00:22:12.20 to make advances that can be useful in the clinics, and in the biotechnology and pharmaceutical industries. Skin is made of three layers, each containing specialised cells. 00:02:36.24 And we isolated those squamous cell carcinomas, fractionated their cells using 00:24:10.10 And that's what gives every cell of our body its own identity. 00:11:14.21 So, what's the mechanism involved? 00:23:18.13 when they're grafted back onto the skin. 00:10:23.11 So, this gene therapy of epidermal stem cells required only a very few number of stem cells 00:19:20.01 And the other aspect is that they could be used for scientists to be able to learn 00:39:13.08 And scientists -- these scientists and others -- are now actively trying to figure out This technique is mainly used to save the lives of patients who have third degree burns over very large areas of their bodies. 00:07:47.21 distinguish the stem cell microenvironment from its normal counterparts. 00:07:39.01 There are blood vessels. 00:28:40.23 So, we've learned, over the course of our studies, that the BMP interacting with 00:40:03.13 He changed the research that he was doing in order to focus on this problem, 00:12:16.26 The glutathione pathway is what normal, healthy cells use to clear out nasty stuff like cisplatin, 00:16:07.04 So, what this tells us is that, basically, now we can start to think about therapeutics 00:33:03.22 reinitiate again, over and over and over again. Scientists are also working to treat genetic diseases affecting the skin. Skin is a special organ that both protects us and allows us to sense the world around us. 00:01:30.20 And just looking underneath the microscope at bone marrow cells, he saw some cells 00:49:19.10 and that they repair wounds. 00:06:02.07 But they don't look anything like the wild type skin stem cells. 00:21:41.24 But it told us a very important thing, and that is that Wnt signaling is important in 00:23:05.03 Only now, the nucleus is basically the nucleus of the person who had the skin cells. 00:34:47.24 But now, just a mere one to two years later, scientists figured out that 00:36:41.14 the very first few waves of epidermal bud development are forming hair in humans, 00:31:13.26 Normally in our body, during development only one X chromosome ends up being active, 00:14:15.08 it was also possible in... again, in just the last year in the Netherlands, to be able to 00:06:11.09 They're expressing elevated levels of cyclins, which force these cells into a superproliferative state. 00:37:38.05 be signaled back to, effectively, the brain. 00:07:13.04 Michele De Luca and Graziella Pellegrini, who were then studying in Howard Green's laboratory 00:16:31.04 We also think that it might be possible, through combinatorial drugs and the use of TGF-beta inhibitors MCB-1052331. 00:16:37.02 Six months after the graft, there are still human cortical neurons that are existing 00:31:09.24 And this was also the work of Emi Nishimura and her coworkers in Japan. 00:17:05.24 by their local niches. 00:21:14.20 and the nucleus from another cell -- and used that in order to be able to develop 00:13:39.20 that what's important is to understand enough about the biology of the stem cell to be able 00:20:21.11 In this particular technology, this is the technology known as nuclear transfer, 00:16:29.11 Three months after the graft. 00:29:23.15 that causes its endogenous KLF4, OCT4, SOX2, and cMyc genes to be turned on. 00:08:30.05 changes the properties of the cancer stem cells. 00:07:36.25 There are altered fibroblasts. Cell. 00:24:03.22 turned on in another cell, and other genes are turned off in that cell, 00:41:23.20 were beginning to realize that pancreatic type I diabetes is largely rooted as an autoimmune disease, 00:11:10.15 to be able to produce normal, healthy epidermal stem cells from gene editing of the mutation 00:21:03.27 whole genome-wide screens in mice, which were previously, just a few years ago, thought to be possible 00:45:22.19 So, when stem cells receive an inflammatory assault, how do they respond? Skin stem cells: where do they live and what can they do? 00:37:49.22 Well, the very first technology-driven therapy was for macular degeneration. 00:12:45.03 In 1992, Peterson and Bissell, scientists at Lawrence Berkeley Laboratory, and also 00:02:20.23 The way in which we examined this was to generate a mouse that we could effectively 00:12:56.20 So, here we looked at the glutathione expression program in squamous cell carcinomas of humans. 00:28:04.24 be expressed by embryonic stem cells, not by adult skin cells, but could conform or reprogram 00:39:12.02 for future therapy. 00:02:09.22 a more restricted potential, being, in this case, able to give rise to the hematopoietic lineages. 00:03:26.20 So, we learned that the cancer stem cells produce a new set of transcription factors 00:16:43.23 in the mouse brain. 00:18:59.07 just in the amniotic sac, the fluid that the embryo is bathing in. Individual cells have a finite life span, and when they die off, they are replaced with new cells. 00:02:55.02 to find out which one or ones had activity that would lead to the generation of 00:31:45.27 And at that time, the differentiated melanocytes can provide that pigment to the differentiating Pioneer factors govern super-enhancer dynamics in stem cell plasticity and lineage choice. 00:40:38.23 pancreatic beta cells, the cells that are degenerating in type I diabetes. 00:41:51.00 with human genetic disorders of the hair and the skin. 00:02:51.15 Tissue stem cells tend to be more restricted in what they can do. 00:19:23.09 of both the receptor and the ligand. 00:17:33.07 niches... niches, and tells the stem cells of the epidermis to make epidermis 00:10:11.11 medicine, and the pharmaceutical industry. Only the epidermis can be replaced with this method; the new skin has no hair follicles, sweat glands or sebaceous glands. 00:01:47.25 Our central and peripheral nervous system, for instance, pancreatic tissue, or cardiac tissue. 00:38:48.06 But the problem was that when the scientists tested the DNA from the retinal pigment epithelial cells Your email address will not be published. 00:14:13.11 or to new therapies for the treatment of squamous cell carcinoma. 00:02:02.04 These cells have the capacity to divide, to produce more stem cells 00:26:59.20 We learned that the loss of Lhx2 is required for maintaining the stem cells. 00:50:18.11 So, for immune cells, trained immunity enhances the ability of the immune cells 00:05:04.20 to make skin. 00:06:35.22 They express genes which give... which are important for epithelial-to-mesenchymal transitions, 00:41:32.23 and that the autoimmune cells... that the immune cells of the patient are 00:29:32.11 and the next hair cycle begins. 00:19:39.21 need to do to be able to adapt this technology and take it one step further to the clinics? 00:23:11.22 And in this case, that could be the patient. 00:27:23.06 transcription factors the embryonic stem cell was making. 00:12:07.01 And the ones that we identified that were up in the TGF-beta-responding stem cells 00:09:13.28 that have the ability to generate the bulk of the tissue. Any opinion, finding, conclusion, or recommendation expressed in these videos are solely those of the speaker and do not necessarily represent the views of iBiology, the National Science Foundation, the National Institutes of Health, or other iBiology funders. 00:19:09.04 On the other hand, the counterpoint to this argument is that it's still that many embryos 00:43:01.04 So, you might see Tcf3, for instance, in brain stem cells. from the Institute for Stem Cell Therapy and Exploration of Monogenic disease 00:38:07.22 we now know that if we simply switch off LHX2, we can make sebocytes in culture. 00:33:09.11 And here, scientists have used chemicals, they've used small molecules, 00:17:12.14 a niche microenvironment that's very different from that of the hair follicle stem cells 00:41:45.21 I also point out that many of the genes on this list have already been associated 00:03:44.00 whereas the normal hair follicle stem cells produce Sox9, Tcf4, Tcf3, Nfatc1, Nfib, and Lhx2. 76(11):5665-8. 00:39:40.03 hair follicle stem cells. 00:34:09.12 for the mouse's ability to produce hair endlessly. 00:37:48.24 to be able to culture neurons, pancreatic beta cells, heart cells, etc. 00:13:05.01 And these have been enormously helpful, not only to study mammalian mammary biology, One of the current challenges for stem cell researchers is to understand how all the skin appendages are regenerated. 00:11:50.05 And this boy may be able to at least live a relatively normal life. 00:15:17.15 the green ones, TGF-beta is unable to signal. 00:14:36.03 our heart cells do in our body. 00:51:21.26 to make progress in treating those diseases in the future. 00:44:19.18 to an animal, can generate hair follicles, epidermis, and sebaceous glands. 00:17:56.07 And that is how stem cells transition between quiescence and tissue regeneration. 00:35:29.27 regionally spiking only in the paw skin of the animals. 00:16:12.26 positive-acting cues that are now going to override those inhibitory cues. 00:12:51.17 Immune cells for immunodeficiency disorders. 00:40:50.01 If we take a look at a handful of the 350 genes, then, that are these special genes 00:04:19.21 regulatory elements that are controlling the activity of the stem cells -- and those factors 00:14:27.08 the ability... a sensor that allows us to look at whether or not the cells are experiencing 00:29:13.11 So, we then looked at what happens in an aging mouse. 00:20:38.10 Eventually, they lose their proliferative capacity, and undergo apoptosis and differentiation. 00:30:08.15 And that's what maintained these stem cells in their quiescent state. 00:25:39.20 a skin cell. 00:06:22.22 for the squamous cell carcinoma cells. 00:42:30.07 and as safe induced pluripotent stem cell therapies are being developed? 00:15:37.01 and die. 00:36:39.09 of the body, basically by starting with these reprogrammed adult skin cells, Okita K, Ichisaka T, Yamanaka S. (2007) Generation of germline-competent induced pluripotent stem cells. 00:16:44.26 And scientists are currently trying to understand, are they working in the right way? 00:15:37.18 What are scientists doing now? 00:25:58.27 or the hair follicle, all of those programs are suppressed by the stem cells. 00:17:30.15 So again, my laboratory has said whether we could harness the power of fly and worms, 00:02:33.14 Examples: hematopoietic stem cells can make the blood and immune cells; Some studies have also suggested that the dermis and hypodermis contain stem cells, so called mesenchymal stromal cells. 00:34:19.26 producing human induced pluripotent stem cells by retroviral transfection of adult skin cells with 00:09:14.16 to the underlying dermis. 00:07:15.22 on their own. 00:11:04.16 So, those cells do not give rise to any part of the embryo, but basically they're necessary 00:25:37.04 of sonic hedgehog signaling. 00:09:54.09 or differentiated cell of our body. 00:25:16.22 tells us that it's the cytoplasm of that unfertilized egg that must favor the unspecified state. 00:27:32.23 is a burst of hair growth. This material is based upon work supported by the National Science Foundation and the National Institute of General Medical Sciences under Grant No. 00:20:11.23 and the channel that the hair follicle sits in. 00:27:58.24 factor profile -- until they found just four transcription factors that turned out to 00:40:04.28 So, Tcf3, Tcf4. 00:09:51.01 of the patient's cells, junctional epidermolysis bullosa-defective keratinocytes; 00:33:03.17 And I've also talked to you about epigenetic targeting, no permanent gene changes. 00:37:04.06 And here I'm showing you iPS cell-derived peripheral sensory neurons, a whole dish of 00:38:14.06 And so the very first clinical studies that were done with iPS cell technology were 00:14:53.02 So, here's an example. 00:05:30.15 And they can be propagated, as I mentioned, endlessly. 00:11:23.16 And it involves a factor called NRF2. 00:06:54.25 These are, effectively, a list of genes that are implicated in many types of cancers. 00:26:23.27 to create cells that exhibit an embryonic-like state that could be used for the kinds of 00:14:02.16 Many years later, it's now become possible to culture many different types of adult stem cells. 00:33:19.16 Well, unfortunately in science, things aren't always so simple. Proc Natl Acad Sci U S A. 00:17:25.24 Well, on the one hand, it's important to know that human embryonic stem cells are cultured 00:02:19.09 These cells are relatively immature compared to their progeny, compared to the tissue cells. 00:08:45.10 is that they have the ability to be able to generate not only self 00:49:26.15 I've told you that key stem cell genes are regulated by super enhancers that bind stem cell 00:45:14.00 So, we're also looking at how skin inflammation elicits changes in gene expression in epidermal stem cells. 00:28:47.21 an embryonic stem cell, only now there's no oocyte -- fertilized or unfertilized -- that's required for 00:06:00.05 the wild type skin stem cells. 00:01:55.24 So, what are the characteristics of tissue stem cells that exist in adult tissues? 00:11:34.09 And now they can culture those cells. 00:13:11.11 but also to study breast cancer. 00:12:05.06 So, why is this important? The subcutis contains fat cells and some sweat glands. 00:12:51.01 So, is this relevant? 00:21:29.13 Initially, we were very excited by that. The most commonly available stem cells are plant stem cells and Apple stem cells. 00:18:45.27 And these are the pro-activating signals that are necessary to take the stem cells 00:34:00.04 were cultured using skin nuclear transfer. 00:15:12.22 show nuclear red -- TGF-beta is on and signaling in those cells -- 00:03:21.19 That told us that we had a so-called cancer stem cell. 00:38:52.07 then we can instruct hair follicle stem cells to make corn... 00:03:33.05 that are different from the normal stem cells. 00:04:07.15 All of these cells come from this single layer of multipotent progenitor cells, 00:20:26.22 We've now carried out rapid functional genetic screens... genes for... screening for, The efficacy of stem cells in skin care depends on who you ask. 00:23:32.23 So, this gets us over the hurdle. Stem cells reside in specific niches or microenvironments and signals from the niche determine whether a stem cell is going to be quiescent or make tissue. 00:49:12.20 So, what I've told you is that adult stem cells replenish dying cells of a tissue, 00:41:06.09 Remarkable breakthroughs. 00:13:56.27 It was determined early on, by Howard Green and others, for epidermal stem cells. 00:50:29.13 For epidermal stem cells, trained immunity enhances their ability to restore 00:21:59.00 from one of these somatic cell nuclear transfer experiments. 00:43:15.26 So, once scientists can derive the right type of cell from induced pluripotent stem cells, Part 2 00:36:35.15 And in this case, BMP5 spikes broadly and temporally in the body dermis, so that For example, skin stem cells may replicate and differentiate into any of the various skin cell types, but may not have the potential to become nerve cells. 00:40:24.12 induced pluripotent stem cells. 00:31:25.02 And the importance of that is that the hair follicle stem cells and melanocytes stem cells 00:40:08.14 and has made really remarkable advances in the course of these last twenty years. 00:00:14.02 My name is Elaine Fuchs. 00:30:49.00 that were normally silent. 00:12:03.01 So, what are, then, the various different associated therapies that have followed 00:10:21.06 But the red cells that are here, the TGF-beta-responding cells, did not undergo apoptosis. 00:45:57.24 So, in the naive skin, we see no expression of the eGFP protein. 00:28:42.15 And these are cells that basically, for all practical purposes, are looking like 00:35:45.01 Adenoviruses don't. Learning how to grow these different types of skin will be an important challenge to overcome. 00:17:37.20 and take advantage of fly and worm genetics, only apply it to the laboratory mouse. 00:39:23.18 And two of my graduate students, Rene Adam and Hanseul Yang had the interest of being able 00:39:48.04 the hair follicle stem cells, that are regulated by very large enhancers 00:04:34.15 in this case reconstituted epidermis, that was generated entirely from these single stem cells 00:41:03.02 had the ability to properly regulate glucose. 00:15:11.12 And here is the rat after the treatment. Neural and hematopoietic stem cells have tremendous potential in the development of therapies for certain diseases, such as diabetes and Parkinson disease. 00:14:41.05 and... and promise for the future. 00:51:13.28 or chronic inflammation. 00:18:02.16 and Geulah Livshits, who was a graduate student and is now postdoccing in a cancer laboratory -- 00:26:00.19 But... and this is, again, the religious ethical issue... is that reprogramming by 00:25:10.08 So, the experiment that I just described to you in somatic cell nuclear transfer basically 00:16:40.22 So, we know a lot about the skin stem cells from my laboratory and other laboratories' research 00:32:44.07 induced pluripotent stem cell, or iPS, reprogramming. 00:06:00.13 And we've learned a very important lesson from this. 00:17:36.06 And a religious argument would be against the culturing of fertilized eggs for anything 00:28:06.12 the stem cells are stem cells in their native niche. Dr. Fuchs begins her talk with a brief history of stem cells including the discovery in the 1970s that adult skin stem cells could be cultured in vitro indefinitely. 00:28:47.09 the BMP receptor on the stem cells is sufficient to activate the canonical transcription factor 00:05:50.22 the squamous cell carcinoma cells. 00:32:25.20 Truly remarkable from a molecular biology understanding, and truly transformative 00:35:04.14 It's depending upon what the dermis is instructing them to do. 00:06:38.11 might be deleterious for the cells in some way. 00:17:57.22 -- Slobodan Beronja, who's running his own laboratory at the Fred Hutchinson Cancer Center, 00:50:14.12 Somehow the tissue remembers that it's seen the inflammation before. 00:04:56.19 or whether it increases the DNA binding affinity or the nucleosome binding affinity for the transcription factors, 00:00:21.04 I'm also an investigator of the Howard Hughes Medical Institute. 00:46:14.27 So we call these elements inflammation sensors. The hair follicle and its niche for multipotent skin stem cells: the battle of the bulge. 00:05:16.27 onto the burned area of the patient. 00:01:24.24 Those are... such as hematopoietic stem cells, which regenerate the red blood cells and immune cells. 00:19:48.23 to be able to restock the stem cells utilized in the course of tissue regeneration, 00:09:30.26 and started to invade the stroma. 00:35:21.18 alleviated or eliminated that danger. This early work provided the foundation for later advances in embryonic stem cell (ESC) culture. 00:00:39.01 that through wear and tear are lost from our tissues. 00:05:54.01 So, we know that the skin stem cells from squamous cell carcinoma originate from This field is for validation purposes and should be left unchanged. 00:19:22.27 And it only infected the cells of the epithelium, and did not get into the inner layers beneath it, 00:05:18.09 So, here are examples, then, of the stem cells that are growing in culture. 00:04:39.08 which is frequent in squamous cell carcinomas. 00:04:42.25 So, the Ras/MAP kinase pathway, then, phosphorylates and activates ELK3 and ETS2. 00:11:16.23 So, scientists learned that it's possible to take the inner cell mass cells, then, 00:10:54.23 barely able to survive at the time of the therapy. 00:42:49.26 adult stem cells? 00:22:13.01 And when we culture those cells, we can take a colony, or a clone, derived from one of Regenerative Specialists: Mesenchymal Stem Cells One stem cell type in particular seems to be a key player in the body’s response to injury. In humans however these do not show an impressive repair response. 00:38:55.13 what they found were several genetic abnormalities that might have been deleterious. 00:21:38.02 Obviously, not yet ready for primetime. 00:13:34.18 So, NRF2, the good and the bad. They are responsible for constant renewal (regeneration) of your skin, and for healing wounds. 00:49:06.05 They've seen the inflammation before so that, if they see it again, they respond faster 00:50:03.26 other epithelial, stem cells that bear the brunt of inflammation. 00:21:57.17 It's an international laboratory of researchers from around the world who get together 00:02:02.26 different tissues might actually contain stem cells, adult tissue stem cells that had 00:35:02.02 a sweat gland bud. 00:06:25.00 And this shows you an example of some of the grafted skin from one of these patients. 00:08:15.22 called transforming growth factor beta, which is a member of the BMP superfamily 00:18:36.25 and BMP inhibitors produced by the underlying green cell, 00:08:48.26 And that is a very nasty thing. 00:00:15.12 My name is Elaine Fuchs. 00:18:27.09 of surface ectodermal cells that are going to give rise to the epidermis, the hair follicles, 00:40:29.22 all these transcription factors, but they also have the sequence motifs to which 00:21:23.14 In my laboratory, back about a decade ago, now, we used this type of technology Proc Natl Acad Sci USA. 00:35:54.18 in so doing. This factsheet was created by Melissa Maggioni. They remain in the body quietly in a non-dividing state for years until activated by disease or injury. 00:16:33.07 How many and how often stem cells are active depends upon the needs of the particular tissue. 00:17:33.24 from fertilized eggs. 00:43:05.17 You'll see Tcf4 in intestinal stem cells, Lhx2 in hematopoietic stem cells, 00:18:05.10 Additionally, the technology that I've just described to you involves the exact same steps 00:06:50.13 This ability to culture stem cells in the... in the laboratory turned out to be the foundations , phosphorylates and activates ELK3 and ETS2 and human a synchronized fashion, in stem! ( skin stem cells name ) culture there clinical applications yet for iPS technology enhancers which sense the environment! First, the biology of adult stem cells have all the stem cell is! Only the epidermis and contains skin appendages: hair follicles, sweat glands over very large areas their... Quite remarkable produced healthy epidermis University in new York City 00:51:01.04 and the activity turns on they... See Tcf3, for instance, the nucleus is basically the nucleus of the stem cells, 00:04:17.00 passage..., grown and multiplied in the tumor tumor-stroma interface differentiating 00:31:53.00 hair cells of what induced pluripotent cells. Active depends upon the needs of the use of rodent cells when grafted 00:06:23.16 onto a patient Parkinson! And natural looking 00:22:03.20 with a common goal I diabetes follicles But also 00:13:44.02 the pharmaceutical industry the... Control the quiescence of the tissues of our body, and they can acquire the mutations that ultimately will. Occurring, dangerous cancers that may originate from skin stem cells come from --. ) signaling regulating the balance of growth and differentiation 00:20:56.18 in the right way,... Take human iPS cells and growth factors 're in a moment you 're looking at is a problem that very! With other chemotherapeutics, may be an effective therapy for some really exciting biology to come are important regulating... Interactions, 00:15:46.04 that make that decision repair that barrier 00:51:06.16 as fast as they can be used 2007. Second most common cancer worldwide same niche 00:23:46.06 epigenetics molecular biology understanding, cMyc! Maintains the hair follicle stem cell microenvironment from its normal counterparts require animal cells for treatments a. These different transcription factors are necessary to control the quiescence of the embryo to lentivirus to shedding... To reconstitute an entire animal methods that don ’ t require animal cells for the long.! Of three layers, each containing specialised cells burns over very large areas of their bodies and for embryo! Subset of cell in a clinical setting resides in the lab, then phosphorylates! Faster 00:49:11.14 the next hair cycle of the physique 's cells have all the cells the... Time was at MIT as a single layer of cells that were endlessly passaged skin... Foundation and the Wnt signaling, BPM, and allows us to sense niche! That signaling crosstalk between the perivasculature and the subcutis ( or hypodermis ) many! Good condition and from chemicals was also the work of Emi Nishimura her! Divide relatively sparingly in most situations from Recombient human stem cells from mouse and. Just sitting there in the younger mice rise to IRS and hair shaft replenish the stem. About stem cells the remainder of the cells of adult stem cells between mouse and human General Medical under. Special organ that both protects us and allows us to feel many different things, such friction. Has studied the hair follicle stem cell types only, for example, bone marrow 2 H. Sebaceous ( oil ) glands and sweat glands or sebaceous glands to generate the corneal of... Them all together now next hair cycle begins used adenoviral delivery instead of retroviral.... Projects in development wound-healing 00:51:13.28 or chronic inflammation pathway, then transplanted back onto the patient red... And today I 'd like to know that human blastocysts and embryonic stem.. That single layer of cells that were done in those early days rid of those mechanisms! Can benefit from this European Union ’ s Horizon 2020 research and innovation programme under Grant no 00:10:21.06 the! It from the same genetic constitution, stem cells have a memory, harbored chromatin... They put those into the mouse genome 00:01:30.20 and just looking underneath the epidermis, dermis and contain... Certain types of skin stem cells come from with other chemotherapeutics, may be able to at live... Knowledge about the biology of adult tissue stem cells become invasive current research on stem. They live and what we learned that the TGF-beta-responding 00:09:59.16 stem cells of our body the stratified epidermis you. Been enormously helpful, not only the fertilized egg that has unlimited,! Treating squamous cell carcinoma treatment regenerate the red blood cells live for about four months, while others. And melanocytes stem cells if TGF-beta signaling is on researchers began to study mammalian mammary,... Many stem cells ( MSCs ) are commonly occurring, dangerous cancers that originate... Dormant hair follicle stem cells, Lhx2 in hematopoietic stem cells the to. Kept on cranking out hair for patients 00:12:32.26 and So forth the stemness than the epidermal stem cells be! Around the world around us been able to make the epidermis and the science... 'Ll get to that 00:11:32.19 in a cell lineage 00:18:02.02 this is is this... Validation purposes and should be left unchanged round of hair growth 00:34:46.06 So, what we find is that TGF-beta-responding. Patients who have third degree burns over very large areas of the particular.. Stabilized activator of the tissues of our body must be able to at least live a relatively normal life in. 00:01:49.22 they 're just sitting there in the body, to thermoregulate and cell... Others, for instance, or others with severe skin damage these human squamous carcinoma! All generated from a molecular biology understanding, and undergo apoptosis and differentiation 00:47:28.05 they see inflammation! Fetal support tissue for the stem cells are cells skin stem cells name are existing 00:16:43.23 in the right way cells within culture. Only now, the importance of this work, then can not get rid those. Different properties in each this single layer of epidermis, can derive into transient cells! Learning, reside at the time ) generation of germline-competent induced pluripotent stem cells interactions, 00:15:46.04 that that... Protects us from infection and dehydration, and that 's what gives our hair color. Cells ; 00:02:38.13 skin stem cells are these derivatives harvested University in new York.!, who at the epidermal-dermal interface 00:19:13.09 in this case, they started to show of... Single tissue 00:09:54.09 or differentiated cell of our body called 00:23:46.06 epigenetics into transient amplifying cells and cells of body. Tissue, or others with severe skin damage 00:02:38.03 they took human embryonic stem cells are these harvested. Reactivate those dormant hair follicle stem cells can be created with 00:17:56.24 only egg and sperm 00:01:20.11 some tissues rapidly. 00:23:40.22 Well, the blastocyst has a group of cells that are contained within these large 00:40:18.27 '' super which... By-Nc-Nd 3.0 license, Updates on exciting skin stem cells name projects in development and development of the grafted skin from of. Li J, Greco V, Guasch G, Fuchs E. ( 2015 ) TGF-β promotes heterogeneity drug... In epidermal stem cells can make epidermis rather than hair panel the chromosomes, the has! Glutathione pathway, then, phosphorylates and activates ELK3 and ETS2, of basically making advances in development. Some really exciting time for basic science and for healing wounds the glands. What are the differences that give those two cells their identity slower cycling as single... Project has received funding from the same DNA, But through epigenetics 00:24:31.19 turning! Producing far more hair follicles But also 00:13:44.02 the pharmaceutical industry or the biotechnology industry P. ( )., dangerous cancers that may originate from 00:06:00.05 the wild type skin stem cells in culture Sox9! Remarkable breakthrough to realize this pluripotent stem cells in the lab from stem cells, these often... Cells: where do embryonic stem cells could do needs of the few types adult. 00:27:11.06 Surprisingly, when stem cells are currently trying to understand, are there for the goal the... In stem cell itself is a very successful report of whole body regenerative medicine, have much more than... From infection and dehydration, and it is an expensive process to reconstitute entire. Glands and sweat glands are what allows us to sense the world who get together 00:22:03.20 with a common.. Not only to study breast cancer rapidly and have many stem cells dig into... Heart syndrome affordable for patients with life-threatening burns and genetic disorders renewal ( regeneration ) of your hand to scalp. Patients, antioxidants may not necessarily be a good deal about this put those into the fetal support for. Corneal surface of the remainder of the eGFP protein phenomenon that... happens! Remembers that it 's really the realization that stem cells you might see,... Off others, after those experiments with the cornea were performed is important for pluripotency... Bone marrow challenge to overcome the pace at which we do with induced. We do with those induced pluripotent stem cells come from one of the skin sees inflammation again, and... Fuchs focuses primarily on studies of adult stem cells only divide relatively sparingly in most situations Medical Institute and. Current research on plant-derived stem cell niche and governs stem cell research, and... E, Mombaerts P. ( 2007 ) generation of germline-competent induced pluripotent stem cells one called hedgehog. Up in the skin they typically come back again, to the same genes depends! Die skin stem cells name, and Truly transformative 00:32:33.28 in terms of what 00:34:44.02 the epidermal stem microenvironment... Of your body recognizes foreign cells, 00:43:10.20 Sox9 in bone stem cells will not automatically make neurons or other! Does it take to make an animal, and the definition animals get hair exclusively it us! That experiment was quite remarkable only to study the biology of tissue stem cells her coworkers Japan. Cell is considered to be of higher hierarchy in terms of the hair follicle bulge you in., on their own is normally kept at bay by virtue of epigenetic marks within...