Chapter 22: Stem Cells, Cell Asymmetry & Cell Death

The text details the derivation of embryonic stem (ES) cells and the critical transcriptional network—involving master regulators like Oct4, Sox2, and Nanog—that maintains pluripotency. Significant attention is given to induced pluripotent stem (iPS) cells, reprogrammed from somatic cells using the Yamanaka factors (KLF4, Sox2, Oct4, and Myc), and their potential in modeling diseases such as ALS and treating conditions like diabetes through regenerative medicine. The chapter then explores the concept of the stem-cell niche, examining how microenvironments regulate stem cell self-renewal and differentiation across various systems, including planarian neoblasts, Drosophila germ-line stem cells, mammalian intestinal stem cells (marked by Lgr5 and regulated by Wnt signaling), and hematopoietic stem cells (HSCs) in the bone marrow. Plant stem cell systems are also compared, highlighting the WUSCHEL-CLAVATA feedback loop in shoot apical meristems. The focus then shifts to the molecular basis of cell polarity and asymmetric cell division, mechanisms essential for generating cellular diversity. Key examples include the intrinsic polarity program in budding yeast mediated by the GTPase Cdc42, the segregation of Par proteins and P granules in the C. elegans zygote, and the antagonistic interactions between the Par, Crumbs, and Scribble complexes in establishing epithelial polarity. The text also covers Planar Cell Polarity (PCP) signaling involving Frizzled and Dishevelled, and the asymmetric division of Drosophila neuroblasts. Finally, the chapter elucidates the pathways of regulated cell death, distinguishing between apoptosis, necrosis, and necroptosis. It outlines the evolutionarily conserved genetic pathways derived from C. elegans (involving CED-3, CED-4, and CED-9) and their vertebrate counterparts. This includes the intrinsic mitochondrial pathway regulated by the Bcl-2 family (balancing anti-apoptotic Bcl-2 against pro-apoptotic Bax, Bak, and BH3-only proteins like Puma and Bad), the release of cytochrome c, and the formation of the apoptosome to activate initiator and effector caspases. The extrinsic death receptor pathway, mediated by ligands like TNF and Fas, is also described, alongside the role of trophic factors (neurotrophins) in neuronal survival and the mechanism of necroptosis involving RIPK1, RIPK3, and MLKL.