Stem Cell Biology Notes PDF

Module 41 Totipotent - each cell can form a new individual; for example, early human embryo (1-3 days) cells. Pluripotent - these cells can form any of over 200 cell types; example: embryonic stem cells [some human blastocyst (5-14 days) cells] Multipotent – these cells are somewhat...

Module 41 Totipotent - each cell can form a new individual; for example, early human embryo (1-3 days) cells. Pluripotent - these cells can form any of over 200 cell types; example: embryonic stem cells [some human blastocyst (5-14 days) cells] Multipotent – these cells are somewhat differentiated, but can still form several tissues; examples: cells from fetal tissue, cord blood stem cells, and adult stem cells A is a stem cell, B is a progenitor cell (a cell that has initiated differentiation), C is a differentiated cell. Professional designates permanent stem cells. The classic example is the Lg5+ CBC cells in the intestine. The progenitor can differentiate into a mature cell. Dedifferentiation is also possible, when a progenitor becomes less differentiated, gains stemness, and transitions into the original multipotent stem cell. Dedifferentiation is also possible, when a progenitor becomes less differentiated, gains stemness, and transitions into the original multipotent stem cell +4 stem cells are generally quiescent under normal conditions and only become active when needed to replace lost CBC stem cells. Wnt signaling and Bmp antagonists are higher at the bottom of the crypt and decrease going up; these tend to promote stem cell self-renewal. BMP, Hedgehog, and Hippo signaling increase going up the crypt and they promote differentiation. Notch signaling also helps control Notch signaling In TA Compartment helps control intestinal cell differentiation via lateral inhibition Higher potency stem cells have greater potential to differentiate into various cell types, while lower potency stem cells are more restricted in their differentiation capabilities. Notch-Dll interactions affect signaling in each cell. o The increased expression of HES1 and decreased expression of Atoh1 and Dll in the Notch-high cells promote differentiation to the absorptive cell lineage. This reinforces the cell fate as a Notch- high and Dll-low cell). o In the Notch-low cells, HES1 expression is decreased, leading to increased Atoh1 expression, which in turn upregulates Dll expression. This reinforces the Notch-low, Dll-high phenotype and promotes differentiation to a secretory cell lineage. Notch signaling is crucial for lateral inhibition  Module 42 In the differentiated cells, enhancers associated with stemness are turned off, while differentiation enhancers are turned on. In the intestinal stem cells, enhancers of both secretory and absorptive lineage genes are in a generally active state. Module 43 Methodological challenges remain, including the need to develop safe and effective delivery systems for stem cell therapies. Embryonic stem cells are the subject of significant ethical and moral debates, with broad social and political implications. Induced pluripotent stem (iPS) cells require further research to ensure they are both effective and safe for therapeutic use. Immune rejection is a concern when using donor cells, though this is not an issue when the cells are derived from the patient. Adult stem cells have limited potency compared to other stem cell types, which may restrict their versatility in treatments. The use of adult stem cells carries risks, including potential mutations and an increased likelihood of cancer development. Patient-derived adult stem cells eliminate the problem of immune rejection, offering a key advantage in personalized therapies. Bone marrow transplantation is a well-established and relatively common success in stem cell-based treatments. Successful stem cell therapy aims to regenerate damaged tissues caused by injury, disease, or aging, rather than providing a permanent cure for all diseases. Aspect EMT (Epithelial-Mesenchymal Transition) MET (Mesenchymal-Epithelial Transition) Normal Occurs during embryogenesis Occurs during embryogenesis Function Role in Cancer cells (possibly cancer stem cells) Cancer cells at distant organs and tissues Cancer undergo EMT, driven by Wnt signaling, ZEB undergo MET, become epithelial again, and transcription factors, SLUG, and other factors. proliferate to form metastatic tumors. EMT makes cells more mesenchymal, invasive, and non-proliferative, enabling metastasis. Phenotype Cells become more mesenchymal, invasive, and Cells become more epithelial and proliferative. Changes non-proliferative. Key Wnt signaling pathways, ZEB transcription Occurs at distant metastatic sites. Factors factors, SLUG, and others. Module 44 Senescent cells are defined by their inability to divide, although they remain metabolically active. Increased cell division is not a cause of senescence; rather, it is the result of cellular stressors like telomere shortening and oxidative damage. Apoptotic cells exhibit nuclear fragmentation, chromatin condensation, and other morphological changes, unlike senescent cells, which are larger and metabolically active. The number of senescent cells tends to increase with age, contributing to age-related diseases and conditions. Cytochrome c is released from the mitochondria and binds to factors to form an apoptosome, which activates caspase 9 in the intrinsic pathway. While caspases are the primary mediators of apoptosis, there are caspase-independent pathways, such as those involving apoptosis-inducing factor (AIF). Deregulated apoptosis can lead to either excessive cell death or insufficient cell death, both of which can contribute to various diseases, including cancer. Executioner caspases are responsible for the degradation of cellular macromolecules, leading to the morphological changes associated with cell death. Bcl-2 family proteins can be either pro-apoptotic or anti-apoptotic and are critical for regulating apoptosis through mitochondrial-mediated pathways. Membrane blebbing is a characteristic feature of apoptosis where the cell membrane begins to bulge out, indicating the early stages of programmed cell death. Bax is a pro-apoptotic protein that promotes apoptosis by facilitating the release of cytochrome c from mitochondria, unlike Bcl-2 and Bcl-xL, which are anti-apoptotic. Nuclear fragmentation is a hallmark of apoptosis, where the nucleus breaks apart as part of the programmed cell death process. Necrosis is typically triggered by external factors such as infection, toxins, or trauma, leading to cell damage and death.