#embryonic stem cells

Stem Cell -l

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.

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Stem Cell -l

The Inner Cell Mass (ICM) of a blastocyst is classified as:

Blastocyst inner cell mass is compact cluster of roughly twenty to thirty cells expressing characteristic pluripotency transcription factor network including Oct4, Sox2, Nanog, Klf2, and surface marker SSEA1 in mouse, TRA-1-60 in human. When microsurgically isolated and cultured, these cells establish embryonic stem cell lines that stably self-renew and differentiate into derivatives of three germ layers in teratomas and contribute to chimeric embryos including germline, confirming pluripotent classification. They are not totipotent because they cannot generate trophoblast autonomously, nor multipotent because not restricted to single germ layer, nor unipotent, highlighting intermediate potency crucial for development progression.

Ref: Evans & Kaufman, Nature 1981; Gilbert, Chapter 6: Inner cell mass pluripotent ESC origin characterization.

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Stem Cell -ll

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

Which transcription factor is NOT involved in maintaining embryonic stem cell pluripotency?

Embryonic stem cell pluripotency depends critically on autoregulatory loop of Oct4, Sox2, and Nanog binding their own and each other's promoters and enhancers of downstream Esrrb, Klf4, Utf1 and chromatin modifiers. These factors recruit Mediator complex and p300 acetyltransferase to maintain open accessible euchromatin at pluripotency loci. p53, a prominent DNA damage sensor, induces cell cycle arrest, apoptosis, and differentiation by activating p21, Bax, and repressing Nanog transcription. Pharmacological inhibition or temporary genetic deletion of p53 dramatically increases somatic reprogramming efficiency, confirming its role as tumor suppressor antagonizing self-renewal rather than supporting network.

Ref: Chambers & Tomlinson, Cell Stem Cell 2009; Gilbert, Chapter 6: Oct4 Sox2 Nanog core versus p53.

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Stem Cell -ll

Which of the following is NOT a natural source of pluripotent stem cells?

Pluripotent cells naturally arise in early embryo as inner cell mass and embryonic stem cell cultures derived therefrom using LIF and 2i conditions, capable of generating three germ layers in differentiation. Induced pluripotent stem cells are engineered artificial surrogates recapitulating pluripotency but are not natural products of mammalian development in vivo. Mesenchymal stem cells from bone marrow, adipose tissue, and umbilical cord are multipotent, differentiating into bone, cartilage, and fat under Runx2, Sox9, PPAR-gamma control, not all embryonic lineages. Thus they are not classified among pluripotent sources, distinguishing broad embryonic potency from lineage-limited stromal potential.

Ref: Dominici et al., Cytotherapy 2006; Gilbert, Chapter 6: Mesenchymal stem cells multipotent not pluripotent source.

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