Stem Cell -lll

Stem Cell -lll

Which of the following chromatin modifications is associated with differentiation?

Differentiation involves stable shutdown of stemness genes and activation of lineage-specific programs through coordinated chromatin remodeling processes. Histone acetylation by p300 and CBP opens embryonic enhancers to allow transcription, while subsequent deacetylation and H3K27 trimethylation via PRC2 polycomb complex closes pluripotency loci. DNA methylation by DNMT3A and DNMT3B at Oct4 and Nanog promoters locks commitment irreversibly. Heterochromatin protein 1-mediated heterochromatin formation silences repetitive elements and alternative lineages. All these modifications including acetylation changes, methylation patterning, and repressive compaction collectively drive progressive developmental restriction effectively.

Ref: Bernstein et al., Cell 2006; Meshorer & Misteli, Nat Rev Mol Cell Biol 2006: Chromatin modifications differentiation.

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Stem Cell -lll

A key characteristic distinguishing stem cells from progenitor cells is:

Stem cells exhibit long-term self-renewal enabling indefinite expansion while retaining potency to generate differentiated progeny through asymmetric or symmetric divisions throughout organismal lifespan. Progenitor or transit-amplifying cells show limited replicative lifespan, gradually exhaust after several divisions, and possess restricted lineage potential with lower telomerase activity. While both can proliferate and differentiate, only stem cells reconstitute entire tissue over organism lifetime and rescue ablated tissue upon transplantation assays. This distinction is demonstrated in hematopoietic reconstitution and epidermal lineage tracing, underpinning regenerative medicine strategies and therapeutic targeting.

Ref: Morrison et al., Annu Rev Cell Dev Biol 1997; Gilbert, Chapter 6: Self-renewal hallmark distinguishes stem from progenitor.

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Stem Cell -lll

Which mechanism is responsible for asymmetric division in stem cells?

Asymmetric cell division requires active segregation of cell fate determinants rather than simple equal cytoplasmic splitting. Conserved polarity proteins such as Numb, Prospero, Brat, and specific mRNAs are localized to one pole by Par3-Par6-aPKC complex and actin-myosin contractility networks. Mitotic spindle alignment then generates daughters with distinct transcription factor dosage, Notch activity, and epigenetic marks leading to divergent fates. Equal partitioning would produce identical self-renewing or differentiating daughters, while complement activation and epigenetic suppression are unrelated immune or regulatory phenomena, not drivers of asymmetry in stem cells.

Ref: Knoblich, Cell 2008; Goldstein & Macara, Dev Cell 2007; Gilbert, Chap 6: Unequal fate determinant partitioning.

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Stem Cell -lll

Pluripotent stem cells can differentiate into:

True pluripotent stem cells derived from inner cell mass, such as embryonic stem cells and induced pluripotent stem cells, can differentiate into derivatives of ectoderm like neurons and epidermis, mesoderm like cardiomyocytes, skeletal muscle, and hematopoietic cells, and endoderm like hepatocytes and pancreatic beta cells under directed induction protocols. They do not normally contribute to extraembryonic trophoblast or primitive endoderm after implantation, distinguishing them from totipotent zygote and early blastomeres. This limited embryonic competence makes them valuable for germ layer disease modelling without placental lineages confounding interpretation.

Ref: Thomson et al., Science 1998; Gilbert, Chapter 6: Pluripotent ESC differentiation into three germ layers only.

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Stem Cell -lll

Which factor prevents differentiation in Drosophila GSCs?

In Drosophila ovary, cap cells located at terminal filament tip secrete Decapentaplegic, activating BMP pathway in adjacent germline stem cells to maintain identity. Phosphorylated Mad-Medea complex directly silences transcription of bag-of-marbles, encoding differentiation-promoting factor required for cyst formation and meiosis entry. High local BMP concentration sustains self-renewal, prevents premature differentiation, and represses bam via heterochromatin modulation. Daughter cells displaced from niche experience BMP attenuation, de-repress Bam, and initiate four synchronous transit-amplifying divisions leading to oocyte and nurse cells, constituting bistable switch.

Ref: Song et al., Development 2004; Gilbert, Chap 6: BMP signaling represses Bam preventing GSC differentiation Drosophila.

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Stem Cell -lll

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

A niche is defined as a local microenvironment that physically anchors, sustains, and instructively controls stem cell behavior through contact, paracrine signals, and extracellular matrix mechanics. Classic examples include basal layer of interfollicular epidermis where hemidesmosomes attach basal keratinocyte stem cells to laminin-rich basement membrane, and adjacent dermal fibroblasts provide Wnt and BMP inhibition to prevent differentiation. Other prototypes are bone marrow endosteal niche, intestinal crypt base, and Drosophila cap cells. Trophoblast, erythrocytes, and mature neurons are differentiated products, not regulatory supportive sites at all.

Ref: Scadden, Nature 2006; Fuchs et al., Cell 2004; Gilbert, Chapter 6: Niche definition skin basal layer example.

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Stem Cell -lll

The Gurdon and Yamanaka experiment demonstrated:

John Gurdon's nuclear transfer experiments in Xenopus and Yamanaka's transcription factor reprogramming collectively proved that differentiation does not entail irreversible genetic alteration or loss of genomic information. Gurdon demonstrated that intestinal nucleus could support cloned tadpoles developing to adult frogs, while Yamanaka showed differentiated fibroblasts return to pluripotency with defined factors alone. Both experiments established epigenetic plasticity as central to development and reversed Waddington landscape conceptually. Recognition transformed concepts of cell fate reversibility, culminating in Nobel Prize 2012, and enabled patient-specific induced pluripotent stem cells.

Ref: Gurdon 1962, Yamanaka 2006, Nobel 2012; Gilbert, Chapter 6: Reversibility of differentiation and pluripotency induction.

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Stem Cell -lll

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

Developmental potency narrows progressively through epigenetic restriction and lineage priming. Zygote and early blastomeres up to two to four cell stage are totipotent, able to produce embryonic plus extraembryonic placenta and yolk sac membranes. Inner cell mass subsequently restricts to pluripotent state, generating ectoderm, mesoderm, endoderm but not trophoblast under normal conditions. Subsequently hematopoietic stem cells become multipotent within blood lineages only, and committed progenitors become unipotent forming one mature type such as erythrocyte or spermatogonium. This hierarchy underlies stepwise differentiation trajectories and transplantation potential.

Ref: Gilbert, Developmental Biology, 12th ed., Chapter 2: Potency hierarchy Totipotent to Unipotent progressive restriction.

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Stem Cell -lll

Which experimental technique was used to identify iPSCs?

Shinya Yamanaka's landmark screen systematically tested 24 embryonic stem cell-associated transcription factors for ability to reactivate Fbx15 beta-geo and endogenous Oct4 promoter in mouse fibroblasts. Through iterative elimination of dispensable candidates, minimal cocktail Oct4, Sox2, Klf4, and c-Myc, termed OSKM, proved sufficient to induce pluripotent colonies contributing to chimeras and germline transmission. Overexpression via retroviral vectors triggered mesenchymal to epithelial transition, global DNA demethylation, and reactivation of endogenous pluripotency network, revolutionizing regenerative biology and earning Nobel recognition for cellular reprogramming concept.

Ref: Takahashi & Yamanaka, Cell 2006; Gilbert, Chapter 6: OSKM factors induce pluripotency in somatic fibroblasts.

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Stem Cell -lll

Which of the following is a false statement about iPSCs?

Induced pluripotent stem cells are engineered by ectopic expression of pluripotency transcription factors in fibroblasts or other somatic cells, erasing somatic epigenetic memory and restoring embryonic-like state. Because they arise exclusively through artificial reprogramming, they are absent from normal embryogenesis and not present in blastocyst or fetus. Naturally occurring pluripotent cells include inner cell mass and epiblast-derived embryonic stem cells. iPSCs share hallmarks of indefinite self-renewal and capacity to form all three germ layers, providing patient-specific models for disease, drug screening, and regenerative approaches without embryo use.

Ref: Yamanaka, Cell Stem Cell 2007; Gilbert, Chapter 6: iPSCs artificial reprogramming not naturally present in embryos.

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Stem Cell -lll

Which of the following mechanisms does NOT regulate stem cell behavior?

Physiological stem cell regulation integrates soluble morphogens like Wnt, BMP, Notch, FGF, niche adhesion via E-cadherin, integrins, extracellular matrix stiffness, metabolic and epigenetic checkpoints that eliminate damaged stem cells. These extrinsic and intrinsic inputs converge on transcription factors governing self-renewal versus differentiation decisions, ensuring tissue fidelity. Random undirected mutations do not constitute a regulatory mechanism; rather they threaten genomic stability and are counteracted by DNA repair pathways, p53 surveillance, and niche culling via apoptosis. Stemness depends on ordered signaling, not stochastic genetic drift or undirected mutagenesis events.

Ref: Morrison & Spradling, Cell Stem Cell 2008; Gilbert, Chapter 6: Niche adhesion, signaling, random mutation not regulatory.

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Stem Cell -lll

What is the function of mesenchymal stem cells?

Mesenchymal stem cells, also termed mesenchymal stromal cells, originate perivascularly in bone marrow and adipose tissue. Defined by CD73, CD90, CD105 positivity and absence of hematopoietic markers CD45 and CD34, they exhibit multipotency limited to mesodermal lineages: osteoblasts synthesizing bone matrix via Runx2, chondrocytes producing cartilage collagen II and aggrecan via Sox9, and adipocytes via PPAR-gamma. Differentiation is driven by Wnt and BMP cues. Unlike hematopoietic or neural stem cells, they do not generate neurons, blood, or gametes under physiological conditions inside the body.

Ref: Caplan, J Orthop Res 1991; Gilbert, Chapter 6: Mesenchymal stem cell multipotency Runx2 Sox9 lineage markers.

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