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Somatic to iPS Cell Reprogramming01:29

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Reprogramming alters the gene expression in somatic cells, transforming them into induced pluripotent stem (iPS) cells over several generations. Scientists can reprogram cells by introducing genes for four transcription factors—Oct4, Sox2, Klf4, and c-Myc (OSKM) by viral or non-viral methods. These factors are also known as Yamanaka factors after Shinya Yamanaka, who first generated iPS cells using mouse skin cells. Yamanaka was awarded the Nobel Prize in Physiology or Medicine in 2012...
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The cells of the blastocyst inner cell mass only remain pluripotent for a short time. This state of pluripotency and self-renewal can be maintained in embryonic stem (ES) cell culture by adding specific chemicals or growth factors to ensure the cells can continue dividing and later differentiate into different cell types. In some cases, the cells are grown on a feeder layer of differentiated cells, which provides the growth factors and extracellular matrix components necessary for stem cell...
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Chromatin modification alters gene expression; therefore, scientists can add histone-modifying enzymes, histone variants, and chromatin remodeling complexes to somatic cells to aid reprogramming into pluripotent stem (iPS) cells.
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Combinatorial gene control is the synergistic action of several transcriptional factors to regulate the expression of a single gene. The absence of one or more of these factors may lead to a significant difference in the level of gene expression or repression.
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Stem cells are undifferentiated cells that divide and produce different types of cells. Ordinarily, cells that have differentiated into a specific cell type are post-mitotic—that is, they no longer divide. However, scientists have found a way to reprogram these mature cells so that they “de-differentiate” and return to an unspecialized, proliferative state. These cells are also pluripotent like embryonic stem cells—able to produce all cell types—and are therefore...
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Related Experiment Video

Updated: Sep 21, 2025

A Two-Step Strategy that Combines Epigenetic Modification and Biomechanical Cues to Generate Mammalian Pluripotent Cells
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Polycomb repressive complex 2 shields naïve human pluripotent cells from trophectoderm differentiation.

Banushree Kumar1,2, Carmen Navarro1,2, Nerges Winblad2,3,4

  • 1Science for Life Laboratory, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.

Nature Cell Biology
|May 31, 2022
PubMed
Summary
This summary is machine-generated.

Polycomb repressive complex 2 (PRC2) maintains early human cell pluripotency and prevents differentiation. This complex uses histone modifications like H3K27me3 to keep key developmental genes poised for later use.

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Area of Science:

  • Developmental Biology
  • Epigenetics
  • Stem Cell Biology

Background:

  • Human embryonic development involves critical lineage decisions, starting with trophectoderm and inner cell mass separation.
  • Naïve human embryonic stem cells (hESCs) originate from the inner cell mass and are crucial for studying early lineage maintenance.
  • Understanding the mechanisms that preserve pluripotency and restrict lineage commitment is vital for developmental biology.

Purpose of the Study:

  • To investigate the role of Polycomb repressive complex 2 (PRC2) in maintaining naïve pluripotency in hESCs.
  • To identify the epigenetic features associated with naïve pluripotency and lineage restriction.
  • To determine how PRC2 inhibition affects hESC fate decisions and differentiation.

Main Methods:

  • Quantitative epigenome profiling to analyze histone modifications, particularly H3K27me3 and H3K4me3.
  • Identification and characterization of bivalent promoters in naïve hESCs.
  • Pharmacological inhibition of PRC2 activity in hESCs.

Main Results:

  • A broad gain of H3K27 trimethylation (H3K27me3) is a hallmark of naïve pluripotency.
  • Naïve hESCs exhibit shared and specific bivalent promoters with PRC2-mediated H3K27me3 and H3K4me3.
  • PRC2 inhibition leads to an 'activated' state with co-expression of pluripotency and lineage factors, followed by trophectoderm or mesoderm differentiation.

Conclusions:

  • PRC2 is essential for maintaining naïve pluripotency and restricting differentiation potential in early human development.
  • PRC2-mediated H3K27me3 and bivalent promoter structures are key epigenetic mechanisms for lineage restriction.
  • PRC2 repression offers an adaptive strategy to control lineage potential during human embryogenesis.