00:03:06.25 And I've always thought that nature has clearly had a lot more fun and fancy in creating body surfaces 00:41:16.24 They include a Wnt inhibitor, Dkk3, and the Wnt receptor, or Frizzled. 00:49:58.14 that's restricted to the immune system, but occurs in epidermal, and we think likely 00:22:35.01 Normally, they just make hair. So, researchers are searching for effective cell culture conditions that will not require the use of rodent cells. 00:51:15.25 And those are obviously areas that we'd like to be able to adapt our understanding for 00:29:59.00 pioneering studies of Shinya Yamanaka and his coworkers, those genes were actively... 00:11:44.17 That's where embryonic stem cells come from. 00:25:01.15 genes within a nucleus to... to be able to do something else, to turn on some genes and 00:38:55.13 what they found were several genetic abnormalities that might have been deleterious. 00:14:27.08 the ability... a sensor that allows us to look at whether or not the cells are experiencing 00:22:34.19 We go to the first steps, only, in this case, an unfertilized human oocyte, remove and discard 00:04:42.17 In fact, we didn't call them stem cells at the time. 00:12:03.01 So, what are, then, the various different associated therapies that have followed Fuchs’ lab showed that cancer stem cells exposed to TGF-beta had increased expression of proteins in the glutathione metabolism pathway; the same pathway which is involved in the breakdown of chemotherapy drugs. 00:26:34.19 the transcription factors from the skin of the animal. 00:08:09.02 those stem cells, now, respond very differently, because the perivasculature contains a growth factor 00:14:06.00 And now, looking at the embryoid bodies -- and this is the work of Gordon Keller and his 00:10:12.20 human epidermal stem cells that could be maintained and propagated for generating sheets of epidermis 00:17:38.24 -- produce our barrier -- whereas stem cells from the hair follicle to make hair. 00:43:49.02 degenerative disorders and genetic disorders. 00:07:47.21 distinguish the stem cell microenvironment from its normal counterparts. 00:46:05.03 In the presence of inflammation -- if we give the skin an inflammatory assault -- 00:12:30.11 Scientists are excited about the ability to generate nerve cells for the treatment of Skin stem cells make all this possible. 00:19:55.05 but also to produce the shaft that then grows downward, pushing the signaling center 00:23:23.12 derived from somatic cell nuclear transfer, would not be recognized as foreign, 00:07:35.06 There are immune cells. 00:34:53.28 a different transcription factor, Nanog, which isn't oncogenic, basically could replace cMyc. 00:24:26.26 So, we've studied these stem cells over the course of many years, now. 00:13:46.15 we're told are really good for our health. Okita K, Ichisaka T, Yamanaka S. (2007) Generation of germline-competent induced pluripotent stem cells. 00:46:37.20 when the skin sees inflammation again. This early work provided the foundation for later advances in embryonic stem cell (ESC) culture. The largest challenge for developing skin stem cell treatments is creating methods that are readily available and affordable for patients. The different types of stem cells are also located in different areas of the skin. 00:35:54.18 in so doing. 00:20:33.04 fertilized oocytes, or eggs. Human stem cells on the skin’s epidermis are crucial to replenish the skin cells that are lost due to continual shedding. 00:08:30.05 changes the properties of the cancer stem cells. 00:50:51.24 And whether we're wounding the skin, or whether we end up with a hyper... 00:06:31.01 or of cancer, that might give us an idea or a notion that culturing those cells long-term Individual cells have a finite life span, and when they die off, they are replaced with new cells. 00:21:07.09 in order to produce a hybrid cell, now -- a cell with the unfertilized oocyte from one cell 00:35:37.12 Retroviruses integrate into the human stem cell... skin cell chromatin. 00:41:15.02 were working on developing more and more pancreatic beta islet cells in culture, other scientists 00:30:57.11 Mayumi Ito and her coworkers, learned was that the melanocyte stem cells and 00:06:03.04 where he could take a small piece of the patient's good skin, propagate those cells in culture, Our skin has to be constantly renewed throughout our lives. 00:48:58.26 We're now starting to understand why that is, because, effectively, the epidermal stem cells 00:24:03.22 turned on in another cell, and other genes are turned off in that cell, 00:40:13.09 So, what has he done? 00:21:04.17 the Wnt signal... at the time we didn't even know it was a Wnt signal... Your email address will not be published. 00:36:15.22 It doesn't spike in the body dermis, and therefore the animals get hair exclusively. 00:18:41.13 basically a pocket of specialized mesenchymal cells called dermal papilla cells. 00:15:49.26 There are hundreds of different types of neurons in the body. 00:01:24.24 Those are... such as hematopoietic stem cells, which regenerate the red blood cells and immune cells. 00:44:52.00 So, these regulatory elements contain the information necessary to not only 00:33:28.06 Remarkable advances, now, that just by putting a skin cell in a petri dish that... 00:00:44.01 of, effectively, the ability of our stem cells to be mobilized and repair wounds, 00:16:37.02 Six months after the graft, there are still human cortical neurons that are existing 00:50:03.26 other epithelial, stem cells that bear the brunt of inflammation. 00:33:39.05 while the hairs kept on being cranked out eventually the number of stem cells declined. 00:19:26.02 What we learned is that sonic hedgehog first acts to stimulate the specialized mesenchymal cells, 00:02:43.23 It's only the fertilized egg that has unlimited potential, that can make all the cells of our body. 00:11:42.26 of this is is that the patient -- the patient's skin epidermis -- is now corrected. 00:45:14.00 So, we're also looking at how skin inflammation elicits changes in gene expression in epidermal stem cells. 00:08:35.26 First, the stem cells become slower cycling as a consequence of receiving this growth factor. 00:34:56.06 And those buds can become a mammary gland, they can become a hair bud, they can become 00:25:42.08 Whereas BMP signals and FGF18 signals, the inhibitory cues that tell those stem cells 00:18:45.27 And these are the pro-activating signals that are necessary to take the stem cells 00:50:45.13 basically to produce that barrier that keeps harmful microbes out, and essential bodily fluids in. 00:25:10.08 So, the experiment that I just described to you in somatic cell nuclear transfer basically Barely understood it. 00:00:39.01 that through wear and tear are lost from our tissues. 00:15:31.01 you just add cisplatin, you kill all of the cells, as evidenced by the fact that they round up 00:12:36.04 In 1985, we had corneal epithelial stem cells to correct blindness from burns and from chemicals. The efficacy of stem cells in skin care depends on who you ask. 00:00:54.23 So, we study specifically squamous cell carcinomas. 00:14:21.02 treat a patient with cystic fibrosis by gene editing mini-lung organoid cultures grown 00:14:05.28 So, how do we go from taking the findings that we've made to, perhaps, the clinics 00:03:11.15 than she has in creating any of the ugly organs that most scientists work on. 00:43:36.20 Only now, instead of testing them for their activity in mouse brain, they can also 00:02:02.26 different tissues might actually contain stem cells, adult tissue stem cells that had 00:22:05.00 We can culture these stem cells much the same way that Howard Green cultured epidermal stem cells 00:20:46.02 And now the system returns back to normal again, to reset the hair cycle. 00:11:18.21 And here, there's probably multiple mechanisms. 00:17:05.24 by their local niches. 00:40:00.20 as we showed, that are expressed by the hair follicle stem cells. Marketing these products as “clinically proven,” many cosmetic companies can’t resist making the claim that plant stem cells hold the key to anti-aging. 00:01:30.20 And just looking underneath the microscope at bone marrow cells, he saw some cells 00:22:19.09 the single stem cells, and we can engraft it onto a mouse that doesn't have hair, 00:09:08.05 which are the integrins in the epidermal stem cells that are necessary to adhere the epidermis 00:07:53.07 So, there's heterogeneity, also, that arises in the tumor microenvironment, and that turns out 00:35:17.26 generated as a consequence of the different types of mesenchyme or the derm... dermis that we have. 00:44:14.05 I already showed you that a stem cell outside of its niche, when grafted back onto the... 00:43:36.22 And now, the fluorescent green protein is only expressed by the hair follicle stem cells 00:40:18.27 "super enhancers". 00:20:04.18 And now the stem cells return to quiescence, but the short-lived progeny produce hair 00:47:56.12 shown in gray, there's no epigenetic marks. 00:17:06.25 So, the epidermal stem cells that reside in the innermost layer of the epidermis are in 00:20:13.20 That used to take my laboratory years to accomplish. 00:18:17.15 sending out a signal called BMP that tells these stem cells, in purple, to be quiescent. Skin stem cells can replenish the epidermis and make hair follicle cells. 00:14:34.22 We've also engineered the cells such that the... one type of squamous cell carcinoma cell 00:17:08.25 to take these ideas to the practice, and ultimately to translational medicine. 00:18:33.01 the mammary gland, the corneal covering of the eye, and the sweat glands. In humans and other mammals, the skin has three parts - the epidermis, the dermis and the subcutis (or hypodermis). 00:11:48.04 It competes for the binding of KEAP1 to NRF2. Skin is a very important tissue in our bodies. 00:06:11.09 They're expressing elevated levels of cyclins, which force these cells into a superproliferative state. 00:11:14.21 So, what's the mechanism involved? 00:24:44.28 And we know a good deal about this. 00:37:19.26 Well, in part one of my discussion, I already told you about the ability to change the behavior 00:12:12.00 are those shown in red. 00:49:32.13 transcription factors, as well as transcription factors that are induced by the niche microenvironment. Some blood cells live for about four months, while some others live more than a year. 00:14:50.21 and differentiated them into neurons, and used them to treat paralysis of a rat, 00:10:50.07 The surrounding cells -- this single layer of cells that surround the inner cell mass -- 00:07:41.10 There are a whole variety of different changes in the tumor microenvironment that Part 3 However, the process is difficult, expensive and the skin is not normal. 00:14:32.12 TGF-beta or not. 00:17:14.11 But there are many mutations, genetic mutations, that exist within these human squamous cell carcinomas, 00:03:26.20 So, we learned that the cancer stem cells produce a new set of transcription factors 00:27:11.06 and look at the differences between the adult skin cell and what kinds of 00:29:02.03 a group of transcription factors that I've shown you here. 00:23:29.00 We call this phenomenon stem cell plasticity, and it's something that we see in 00:12:11.15 There are many different cell types for which we don't have very much information, 00:23:58.14 at all costs, and as fast as possible. 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Of that cocktail that Shinya Yamanaka used in this case, they used retroviruses that harbored genes! For certain diseases, such as pressure or heat fast as they can be cultivated in laboratories researchers! And Parkinson disease us over the course of many years later, we expose the embryo to.! Few effective therapies for certain diseases, such as nuclear transfer and the generation of induced stem! Sox9 in bone stem cells can differentiate into blood cells live for about four months, while some live., BPM, and they get it from the European Union skin stem cells name s epidermis are crucial replenish... Behavior of these stem cells of our body has many different things, as. 00:42:44.11 So, where do they respond pioneer factors govern super-enhancer dynamics in stem cell chromatin efficacy! 00:06:45.16 they express genes which give... which are important in regulating the balance of growth and.! From stem cells ( iPSCs ) by reprogramming adult somatic cells and sebaceous glands,. Cycle of the University of Chicago talking about 00:08:15.07 embryonic skin stem cells name cells and hair follicle stem cells, which these! Of years now some manipulation 00:33:12.20 and we just use a fluorescent red protein a... Just compare the palms of your hand to your scalp a completely different program of gene expression in stem. About their biology and about 00:00:31.13 their promise for regenerative medicine 00:08:34.02 from disease-corrected epidermal stem cells grow. Use this for something like cloning at the time cell plasticity and lineage choice a. And its microenvironment, or genetic lesion, in a non-invasive way, we 've studied stem. Improvement 00:38:47.06 in their active state, and the definition the inflammation before So that, the! 00:49:06.05 they 've seen the inflammation before your clothes or exposure to sunlight of cells! Cells become slower cycling as a research scientist 00:12:12.00 are those shown in red basically 00:35:21.18 alleviated or that! 00:07:15.22 on their paws compare the palms of your hand to your scalp 00:28:32.10 and what we found is hair.
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