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#stem cell biology

17 public questions tagged with this topic.

A transit-amplifying cell is:

Stem cell hierarchy includes long-lived quiescent stem cells, short-lived rapidly cycling transit-amplifying cells, and terminally differentiated cells. Transit-amplifying cells are committed progenitors derived from stem cell division, undergoing limited rounds of symmetric divisions to expand progenitor pool before terminal differentiation. Found in intestinal crypts, epidermis, and testes, they increase proliferative output while protecting stem cells from replication stress and mutation accumulation. They express differentiation markers like EGF receptor and have reduced self-renewal. Understanding this intermediate amplification stage explains how small stem pools generate large numbers of differentiated tissue cells efficiently.

Ref: Potten & Loeffler, Development 1990; Gilbert, 12th ed., Chapter 6: Transit-amplifying cells.

Which of the following can be derived from mesenchymal stem cells?

Mesenchymal stem cells are multipotent stromal cells from bone marrow, adipose, and perichondrium with mesodermal lineage restriction. They differentiate into cartilage, bone, and adipose tissue through master regulators Sox9 for chondrogenesis, Runx2 and Osterix for osteogenesis, and PPAR-gamma for adipogenesis. Cartilage formation involves condensation, Sox9-driven collagen type II and aggrecan expression, and requires TGF-beta signaling. While transdifferentiation to neurons or islet cells has been reported artificially, physiological derivatives remain skeletal tissues. Thus cartilage represents a canonical natural product of mesenchymal stem cell differentiation.

Ref: Caplan, J Orthop Res 1991; Gilbert, 12th ed., Chapter 6: Mesenchymal differentiation.

Which adult tissue is NOT known to have resident adult stem cells?

Adult tissues with turnover retain resident stem cells in specialized microenvironments. Brain harbors neural stem cells in subventricular zone and hippocampal dentate gyrus, muscle contains satellite cells beneath basal lamina, liver possesses oval cells and facultative progenitors for regeneration. Mature red blood cells are terminally differentiated, enucleated, anucleate biconcave discs lacking DNA, ribosomes, and proliferative capacity. They cannot divide or act as stem cells and are themselves products of hematopoietic stem cells. Their short lifespan of about 120 days requires continuous replacement from bone marrow, not intrinsic self-renewal within circulation.

Ref: Alberts, Molecular Biology of the Cell, 6th ed., Chapter 22: Adult stem cell niches.

Which factor is required for maintaining the pluripotency of embryonic stem cells?

Pluripotency in embryonic stem cells depends on a core transcriptional circuit centered on Oct4, Sox2, and Nanog. Oct4, a POU domain transcription factor, activates self-renewal genes and represses differentiation drivers such as Cdx2 and Gata6. Its dosage is critical; too low triggers trophectoderm differentiation, too high pushes toward primitive endoderm and mesoderm. Oct4 collaborates with LIF-STAT3 and FGF signaling to sustain open chromatin and prevent lineage commitment. Loss of Oct4 leads to rapid differentiation, making it indispensable for maintaining the undifferentiated, unlimited proliferative state of embryonic stem cells.

Ref: Gilbert, Developmental Biology, 12th ed., Chapter 6: Core pluripotency factors Oct4, Sox2, Nanog.

The term population asymmetry in stem cell biology refers to:

Population asymmetry describes a tissue-level strategy for stem cell maintenance where balanced output emerges from the population, not from every single division. Individual stem cells may divide symmetrically producing two stem cells or two differentiating daughters, or asymmetrically producing one of each. Across the niche, stochastic choices average to maintain constant stem cell numbers while supplying differentiated cells. This contrasts with invariant single-cell asymmetry where each division is strictly asymmetric. Intestinal crypts and epidermal basal layer demonstrate population asymmetry regulated by Wnt and niche signals, ensuring robust homeostasis despite random individual fates.

Ref: Watt & Hogan, Science 2000; Gilbert, 12th ed., Chapter 6: Population asymmetry model.

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.

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.

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.

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.

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.

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.

Which stem cell type is responsible for hematopoiesis?

Hematopoiesis throughout adult life depends on rare hematopoietic stem cells located in bone marrow endosteal and perivascular niches near sinusoids. These CD34 positive, lineage negative, Sca1 positive cells self-renew and generate common myeloid and common lymphoid progenitors that sequentially produce erythrocytes, platelets, neutrophils, monocytes, B and T lymphocytes. Transplantation of single HSC can reconstitute entire blood system of lethally irradiated recipients, demonstrating multipotency. Totipotent cells form extraembryonic tissues, neural stem cells generate glia and neurons, mesenchymal cells generate bone and stroma, not hematopoietic lineages robustly.

Ref: Weissman, Science 2000; Orkin & Zon, Cell 2008: Hematopoietic stem cells multipotent blood formation.