Stem Cell -ll

Stem Cell -ll

What is the key feature that distinguishes stem cells from progenitor cells?

Stem cells are defined functionally by sustained ability to self-renew over extended time, frequently spanning whole organismal lifespan, contrasting sharply with transient amplifying progenitors that perform limited rounds of rapid division before terminal differentiation and exhaustion. Unlimited self-renewal is supported by high telomerase activity, avoidance of cellular senescence via Bmi1 polycomb repression of Ink4a locus, and asymmetric segregation of damaged proteins and old mitochondria. Multipotency alone does not guarantee stemness, as multipotent progenitors can exhaust quickly. Hence long-term repopulating capacity and serial transplantation remain functional gold standards distinguishing genuine stem cells from short-lived progenitors in experimental biology.

Ref: Shenghui et al., Birth Defects 2005; Gilbert, Chapter 6: Self-renewal unlimited distinguishes stem from progenitor.

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Which type of chromatin modification is associated with stem cell differentiation?

Stem cell differentiation is accompanied by dramatic widespread chromatin reorganization from open to restrictive configuration. Pluripotent cells exhibit globally open euchromatin enriched in activating H3K9 acetylation and H3K4 trimethylation marks, maintaining accessibility of self-renewal genes like Nanog. Upon lineage commitment, histone deacetylases remove acetyl groups, H3K27 methyltransferase EZH2 component of PRC2 deposits repressive marks, DNA methyltransferases methylate CpG islands of Oct4 and Nanog promoters, and heterochromatin protein 1 consolidates constitutive heterochromatin foci at repeats. These coordinated modifications collectively silence pluripotency program and permanently lock lineage-specific expression patterns essential for stability.

Ref: Bernstein et al., Cell 2006; Spivakov & Fisher, Nat Rev Genet 2007: Chromatin modifications differentiation bivalency.

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Which of the following is an example of a stem cell niche?

Skin epidermis represents archetypal stratified continuously renewing tissue where basal keratinocytes attach firmly to collagen IV and laminin-rich basement membrane via hemidesmosomes and integrin alpha6beta4. This basal compartment houses Krt14-positive, p63-positive, slow-cycling stem cells that divide asymmetrically, generate transit-amplifying daughters, and differentiate upward forming spinous, granular, and cornified layers providing barrier. Mechanical tension and Wnt/BMP signals from underlying dermal fibroblasts regulate this highly organized niche. Cardiac muscle, mature neurons, and osteocytes are largely post-mitotic differentiated cells with minimal regenerative stem reserve, not examples of active regulatory niches sustaining self-renewal long-term.

Ref: Blanpain & Fuchs, Annu Rev Cell Dev Biol 2009; Gilbert, Chapter 6: Skin basal layer niche example.

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Which statement is false regarding embryonic stem cells?

Embryonic stem cells originate from careful isolation and sustained culture of inner cell mass of preimplantation blastocyst, typically embryonic day 3.5 to 4.5 in mice, dependent on leukemia inhibitory factor and dual inhibition 2i blocking MAPK and GSK3 to prevent differentiation. Trophoblast comprises outer epithelium forming future placenta, expressing Cdx2 and Eomes, separated by first fate decision driven by Hippo signaling. Deriving ESCs from trophoblast contradicts established lineage; embryonic cells are not trophectoderm derivatives and cannot contribute efficiently to placenta inside chimeras.

Ref: Rossant, Stem Cells 2008; Gilbert, Chapter 5: ICM versus trophoblast lineage ESC origin not trophoblast.

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Stem Cell -ll

The correct combination of transcription factors for iPSC generation is:

Original Yamanaka cocktail clearly demonstrated four transcription factors sufficient to convert mouse and human fibroblasts to embryonic stem-like state functionally and transcriptionally. Oct4 is pituitary octamer transcription factor essential for inner cell mass identity and epiblast maintenance, Sox2 partners directly with Oct4 on composite motifs, Klf4 Krüppel-like factor regulates proliferation while suppressing somatic gene expression, c-Myc oncogene enhances chromatin accessibility, glycolytic metabolism, and proliferation kinetics. Later refinements replaced c-Myc with L-Myc or omitted it entirely to reduce tumorigenicity, while Nanog and Lin28 serve as alternative supplements. Core OSKM remains gold standard for iPSC generation protocols universally.

Ref: Takahashi & Yamanaka, Cell 2006; Yu et al., Science 2007: OSKM combination iPSC generation standard.

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What is the correct order of lineage commitment in hematopoietic differentiation?

Early embryonic hierarchy commences from totipotent zygote capable of forming whole organism including extraembryonic placenta and yolk sac membranes required for implantation. First lineage decision segregates trophectoderm outer epithelium, leaving inner cell mass as pluripotent source of epiblast which later forms three germ layers ectoderm, mesoderm, endoderm through gastrulation. Progressively, definitive hematopoietic stem cells arising in aorta-gonad-mesonephros region become multipotent blood-restricted, while subsequent progenitors such as common myeloid progenitor and later megakaryocyte-erythroid progenitors become increasingly unipotent. This sequential restriction mirrors epigenetic silencing of potency genes.

Ref: Gilbert, Developmental Biology, 12th ed., Chapter 6: Totipotent to Unipotent lineage commitment stepwise restriction.

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Which of the following is NOT a function of stem cells?

Stem cells actively participate in tissue development, continuous renewal, repair after injury, and homeostatic maintenance through balanced self-renewal and differentiation, secreting trophic and immunomodulatory factors that modulate niche environment and immune response. Apoptosis is programmed cell death executed by intrinsic and extrinsic caspase cascade leading to orderly elimination of damaged, redundant, or infected cells, characterized by membrane blebbing, chromatin condensation, DNA fragmentation, and phagocytic clearance without inflammation. It is not a constructive synthetic function of stem cells but rather a quality control mechanism sometimes activated in stem cells themselves to prevent propagation of potentially oncogenic mutations.

Ref: Fuchs & Blau, Cell Stem Cell 2020; Gilbert, Chapter 6: Stem cell functions regeneration versus apoptosis distinction.

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Stem Cell -ll

Which stem cell niche is responsible for intestinal regeneration?

Intestinal epithelium renews remarkably every three to five days driven by rapidly cycling Lgr5-positive crypt base columnar cells intercalated between Paneth cells at crypt bottom. Paneth cells supply essential Wnt3, epidermal growth factor EGF, and Notch ligands Dll1 and Dll4, sustaining high Wnt beta-catenin activity essential for stem proliferation. Definitive lineage tracing and single-cell organoid formation assays confirm Lgr5 cells are multipotent self-renewing stem cells generating enterocytes, goblet, enteroendocrine, and Paneth progeny. Ablation experiments demonstrate niche dependence: loss of Paneth or Wnt signals triggers rapid stem cell differentiation and crypt collapse.

Ref: Barker et al., Nature 2007; Sato et al., Nature 2009: Intestinal Lgr5 crypt base columnar niche regeneration.

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Which type of stem cell division results in an increase in stem cell number?

Symmetric self-renewing division produces two daughters both retaining stem character, full self-renewal transcriptional program, and niche responsiveness, thereby increasing absolute stem cell number inside tissue. This mode dominates during development to rapidly expand progenitor pools, during wound healing to repopulate emptied niches, and in culture systems where niche constraints are experimentally relaxed. Mechanistically, mitotic spindle orientation parallel to niche basement membrane places both daughters within Wnt-rich microenvironment, preserving expression of Lgr5 and other stem markers. Conversely asymmetric division maintains constant numbers, while symmetric differentiating divisions generate two committed cells causing contraction.

Ref: Watt & Hogan, Science 2000; Morrison & Kimble, Nature 2006: Symmetric self-renewal expands stem pool.

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Spermatogonial stem cells are classified as:

Spermatogonial stem cells reside along basement membrane of seminiferous tubules within specialized niche maintained by Sertoli cells producing glial-derived neurotrophic factor GDNF and fibroblast growth factor FGF2. In steady-state spermatogenesis they undergo self-renewing divisions to maintain pool and simultaneously produce differentiating spermatogonia that ultimately yield haploid spermatozoa through meiosis. Although capable of long-term self-renewal like other adult stem cells, lineage tracing demonstrates in vivo they generate only sperm lineage, and during prolonged culture can regain pluripotency if reprogrammed. Under physiological conditions they are classified as unipotent committed to male gamete lineage.

Ref: De Rooij & Russell, Reproduction 2000; Kanatsu-Shinohara, Cell 2003: Spermatogonial stem cells unipotent.

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Which of the following factors is not an extracellular signal for stem cell regulation?

Stem cell niches provide essential extrinsic regulation via secreted morphogens including Wnt family promoting self-renewal and proliferation, Hedgehog patterning tissue boundaries, fibroblast growth factors supporting survival and growth, BMP gradients restricting stemness outside niche, and Notch juxtacrine signaling maintaining undifferentiated state. Intracellular apoptotic executioners such as caspases are downstream intracellular effectors of cell death programs, not secreted extracellular ligands that instruct fate choice through receptors. While niche stress can trigger caspase activation to eliminate damaged stem cells for quality control, caspases themselves do not function as instructive niche signals governing identity or lineage specification.

Ref: Gilbert, Developmental Biology, 12th ed., Chapter 6: Wnt Hedgehog FGF niche signals versus intracellular caspases.

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Which tissue does NOT contain adult stem cells?

Adult or tissue-specific stem cells populate most organs possessing high turnover or regenerative demand, including neural subventricular zone progenitors, hepatic oval cells, muscle satellite cells, and epidermal basal layer keratinocytes. They maintain full genomic complement, DNA repair capacity, and mitotic competence enabling self-renewal. Mature mammalian red blood cells extrude nucleus, ribosomes, and organelles during terminal differentiation steps to accommodate maximal hemoglobin content and enhance vascular deformability. Lacking chromatin, transcription, and division machinery, they cannot dedifferentiate or serve as stem cell reservoir, making them incapable of supporting sustained blood cell production despite abundance.

Ref: Gilbert, Developmental Biology, 12th ed., Chapter 18: RBC enucleation terminal differentiation no stem cells.

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