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#iPSCs

7 public questions tagged with this topic.

Stem Cell -l

Which statement about induced pluripotent stem cells (iPSCs) is false?

Induced pluripotent stem cells are engineered by ectopic expression of Yamanaka factors Oct4, Sox2, Klf4, c-Myc in somatic fibroblasts or blood cells, resetting epigenome to embryonic-like state. They self-renew indefinitely and differentiate into derivatives of three germ layers, useful for disease modeling and regenerative medicine without embryo destruction. Unlike embryonic stem cells isolated from blastocyst inner cell mass, iPSCs do not exist naturally in embryos; they require artificial reprogramming. They retain epigenetic memory and potential tumorigenicity, highlighting distinction between natural embryonic pluripotency and laboratory-induced pluripotency.

Ref: Takahashi & Yamanaka, Cell 2006; Gilbert, 12th ed., Chapter 6: iPSC reprogramming.

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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 -ll

Which of the following statements about iPSCs is false?

Induced pluripotent stem cells are artificially created in laboratory by delivering defined pluripotency-associated factors into differentiated somatic cells such as dermal fibroblasts, triggering extensive epigenetic reprogramming and transcriptional reset, not occurring spontaneously during normal embryogenesis or adult homeostasis. In vivo pluripotent cells are restricted to transient inner cell mass and epiblast stages before gastrulation. iPSCs require viral or non-viral genetic manipulation, mesenchymal-to-epithelial transition intermediate, and selection for reactivated endogenous pluripotency markers. Misconstruing them as naturally present in embryos confuses engineered models with endogenous developmental states and distinct regulatory logic involved.

Ref: Yamanaka Nature 2012 Review; Gilbert Chapter 6: iPSCs engineered not naturally present in embryos fact.

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Stem Cell -ll

Induced pluripotent stem cells (iPSCs) can be generated by introducing which factors?

Induced pluripotent stem cells are produced by transient overexpression of embryonic transcription factors that epigenetically reset somatic genome toward embryonic state. Yamanaka factors Oct4, Sox2, Klf4, and c-Myc disrupt fibroblast transcriptional program, induce mesenchymal to epithelial transition, demethylate pluripotency enhancers, and reactivate endogenous Oct4, Nanog, Esrrb circuitry necessary for self-renewal. Klf4 and c-Myc facilitate proliferation and chromatin opening. Protocols employ retroviral, Sendai virus, mRNA, or episomal delivery with varying efficiency. Resulting iPSCs are molecularly and functionally similar to embryonic stem cells, offering isogenic models without embryo destruction.

Ref: Takahashi et al., Cell 2007; Gilbert, Chapter 6: Yamanaka factors Oct4 Sox2 Klf4 c-Myc iPSC generation.

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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

Induced pluripotent stem cells (iPSCs) are created by introducing:

Yamanaka reprogramming showed somatic fibroblasts can be reset to pluripotency by ectopic expression of core pluripotency transcription network via retroviral vectors. Oct4 and Sox2 form heterodimer activating Nanog enhancer and auto-regulatory loop, Klf4 co-activates and suppresses p53 apoptosis, c-Myc enhances proliferation and chromatin remodeling facilitating demethylation of Oct4 promoter and reactivation of endogenous pluripotency circuitry. These four factors induce embryonic stem cell-like state expressing alkaline phosphatase, SSEA4, Tra-1-60, able to form teratoma containing three germ layers. Replacement of oncogenic c-Myc with L-Myc or Lin28 improves safety. Combination distinguishes iPSCs from growth factor cocktails and differentiation protocols.

Ref: Takahashi and Yamanaka, Cell 2006, Induction of Pluripotent Stem Cells by OSKM Factors.

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