#pluripotent stem cells

Stem Cell -l

Which experiment first demonstrated the existence of pluripotent stem cells?

Pluripotency concept evolved from teratocarcinoma studies showing embryonal carcinoma cells could contribute to tissues. The definitive demonstration came with isolation of mouse embryonic stem cells in 1981 by Evans and Kaufman and independently by Martin. Cultured inner cell mass cells on feeder layers with LIF remained undifferentiated, expressed alkaline phosphatase, formed teratomas containing three germ layers, and contributed to chimeras including germline. This proved stable pluripotent lines exist in culture. Cloning Dolly and mesenchymal stem cell discovery addressed totipotency reversal and multipotency, not primary pluripotency proof.

Ref: Evans & Kaufman, Nature 1981; Gilbert, 12th ed., Chapter 6: Mouse ES isolation.

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Stem Cell -l

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

Pluripotent stem cells naturally originate from early embryonic sources capable of forming all three germ layers but not extraembryonic tissues. The inner cell mass of blastocyst, embryonic stem cells derived from it, and induced pluripotent stem cells created by reprogramming share core pluripotency networks Oct4, Sox2, Nanog. Bone marrow harbors multipotent hematopoietic and mesenchymal stem cells, not pluripotent cells under physiological conditions. It supports blood formation and stromal lineages within mesodermal limits. Distinguishing natural pluripotent origins from multipotent adult reservoirs prevents confusion about embryonic versus adult potency.

Ref: Gilbert, Developmental Biology, 12th ed., Chapter 6: Pluripotent stem cells and inner cell mass.

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Stem Cell -l

Induced pluripotent stem cells (iPSCs) are:

Induced pluripotent stem cells are adult somatic cells such as skin fibroblasts reprogrammed to embryonic stem-like state through forced ectopic expression of defined transcription factor cocktail Oct4, Sox2, Klf4, c-Myc, effectively overriding somatic epigenetic landscape and silencing fibroblast programs. Reprogramming involves sequential ordered events: mesenchymal to epithelial transition, stochastic activation of alkaline phosphatase, progressive demethylation of Oct4 distal enhancer, reactivation of endogenous pluripotency circuitry including Nanog and telomerase restoration. Resulting iPSCs do not exist naturally during normal ontogeny, but are laboratory constructs exhibiting unlimited self-renewal and tri-lineage differentiation offering isogenic disease models and potential autologous cell therapy platforms translationally.

Ref: Takahashi & Yamanaka, Cell 2006; Gilbert, Chapter 6: iPSCs reprogrammed from differentiated somatic cells methodology.

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Stem Cell -l

A significant difference between pluripotent and totipotent stem cells is:

Totipotent cells, by forming trophectoderm lineage and primitive endoderm plus embryonic lineages, robustly support full fetal development including formation of placenta and yolk sac membranes essential for maternal-fetal nutrient exchange, gas exchange, and immunoprotection during implantation. Pluripotent cells, such as inner cell mass-derived embryonic stem cells cultured in vitro, efficiently form ectoderm, mesoderm, endoderm derivatives like neurons, muscle, gut epithelium, but contribute poorly to extraembryonic trophoblast without genetic manipulation or forced Cdx2 expression. This molecular restriction reflects epigenetic silencing of trophoblast program via Oct4-mediated repression of Cdx2, illustrating progressive narrowing of fate potential as development proceeds forward.

Ref: Rossant, Stem Cells 2008; Gilbert, Chapter 5: Totipotent extraembryonic capability versus pluripotent restriction difference.

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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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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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