Regulated Cell Death (Apoptosis) Ch.22

Pluripotent stem cells (neoblasts) are vital for regeneration in organisms like planarian flatworms.
In mammals, sperm compete to fertilize an egg, where successful sperm fusion triggers intracellular calcium influx.
This calcium influx causes cortical granules to release contents, forming a fertilization membrane that prevents polyspermy.
The resultant fertilized egg (zygotic) has a diploid nucleus after the fusion of haploid gamete nuclei (one from each parent).

Following fertilization, the embryo undergoes cleavage, leading to rapid cell divisions without significant growth.
At the eight-cell stage of the embryo, all cells (blastomeres) are totipotent, capable of forming all tissues including the placenta.
As the embryo develops into the 16-cell morula, some cells will differentiate into the inner cell mass (ICM) and the trophectoderm.
Totipotency is lost past the eight-cell stage; the ICM becomes pluripotent, eligible for embryonic stem (ES) cell culture, while trophectoderm leads to placental tissues.

Embryonic Stem Cells: Cultured ES cells retain pluripotency; they divide symmetrically while maintaining potential to differentiate across all cell types (except extraembryonic).
Uses: ES cells unravel gene expression networks, potential replacements in therapies and uncovering developmental biology aspects.

Groundbreaking research reveals iPS cells can be generated from somatic cells through specific transcription factors (KLF4, Sox2, Oct4, and Myc).
iPS cells demonstrate properties similar to ES cells, presenting valuable applications in biology and medicine, enhancing our understanding of differentiation pathways.

Adult stem cells are multipotent. They can give rise to specific cell types and are crucial for tissue maintenance and repair.
Adult stem cells undergo asymmetrical division to maintain their populations while generating differentiated cells, exemplified by hematopoietic stem cells producing all blood cells.

Asymmetric cell division: Yields different daughter cells with distinct fates. A notable example is in Drosophila, where stem cells produce progenitor and differentiated cells in a hierarchical model.
Cell lineage: A tree-like depiction of development illustrating progression from stem cells to specialized cells.

Niche: The microenvironment that sustains stem cells, providing necessary signals for maintaining their undifferentiated state while regulating their cell cycle.
Stem Cells in Vertebrates: Typically multipotent; capable of giving rise to several differentiated cell types found in the organism.
Planarians: Contain both lineage-specific neoblasts and pluripotent clonogenic neoblasts crucial for their remarkable regenerative capabilities. Research suggests that existing stem cells can dedifferentiate and revert to a pluripotent state akin to those in embryos.

Stem cells self-renew ideally through asymmetric divisions, also capable of symmetric division under specific conditions for regenerative responses.
Example: Intestinal stem cells continuously regenerate epithelial cells through lineages progressing from progenitor cells to differentiated epithelial cells such as enterocytes and Paneth cells.

Stem cells dynamically adapt their function in response to injuries, rapidly proliferating and replenishing differentiated cells as needed, showcasing the plasticity in their behavior across different tissues.

Cell Polarity: Necessary for asymmetrical division, affecting how daughters' contents are divided and influencing their fates and functionalities.
Cells experience directional signals, initiating polarization crucial for proper function in complex tissues, such as neurons or gut epithelium.

Signals (e.g., Wnt, Notch) and cytoskeletal reorganizations create carefully regulated asymmetries that guide the fate of daughter cells in early development.

Apoptosis: An evolutionarily conserved form of programmed cell death crucial during development for establishing tissue structure and function.
Results in well-defined cellular morphologies; the dying cells shrink and form safe apoptotic bodies, preventing inflammation.
Necroptosis: A regulated form of necrosis that inflicts inflammation through cellular rupture, often activated in response to infection or organ injury.

In vertebrates, apoptosis is primarily triggered through the mitochondrial death pathway involving Bcl-2 family members and caspase activation.
Anti-apoptotic Proteins: Like Bcl-2 inhibit apoptosis; pro-apoptotic proteins (like Bax) promote mitochondrial membrane pore formation, culminating in cytochrome c release, activating caspases.

While apoptosis is a controlled process, necrosis is a pathological state incited by stress, leading to inflammation. It’s important to differentiate between these cellular fates in the context of therapy and disease management.
Cytokines such as TNFα and Fas ligand can initiate apoptosis through binding to death receptors, leading to widespread cellular effects including necroptosis in the absence of a clear apoptotic pathway.

Totipotent cells give rise to all cell types; pluripotent cells can form various tissues except extraembryonic ones.
Cell death modulation: Critical in maintaining cell populations during development and response to injury.
The interplay of external signals (trophic factors) sustains stem cell populations while tightly regulating differentiation.

Define the differences between totipotent, pluripotent, and unipotent stem cells.
Describe how intestinal and hematopoietic stem cells are established and their roles in tissue maintenance.
Explain how feedback systems regulate stem cell populations in both animal and plant systems.
Discuss how apoptosis pathways can lead to therapeutic advancements and the role played by iPS technology in regenerative medicine.