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Chromatin Modification in iPS Cells01:32

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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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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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Overview of Transposition and Recombination02:13

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Transposons make up a significant part of genomes of various organisms. Therefore, it is believed that transposition played a major evolutionary role in speciation by changing genome sizes and modifying gene expression patterns. For example, in bacteria, transposition can lead to conferring antibiotic resistance. Movement of transposable elements within the genetic pool of pathogenic bacteria can aid in transfer of antibiotic-resistant genetic elements. In eukaryotes, transposons can carry out...
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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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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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Transposable element activity captures human pluripotent cell states.

Florencia Levin-Ferreyra1,2,3,4, Srikanth Kodali1,2,3,4, Yingzhi Cui1,2,3,4

  • 1Stem Cells and Regenerative Medicine Center, Baylor College of Medicine, Houston, TX, USA.

EMBO Reports
|December 12, 2024
PubMed
Summary
This summary is machine-generated.

Transposable elements reveal distinct human pluripotent stem cell states. A novel reporter system tracks pluripotency transitions and identifies safeguards like NSD1 and FUS, advancing developmental biology research.

Keywords:
DNA DamageEmbryonic Stem CellsPluripotencyTotipotencyTransposable Elements

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Area of Science:

  • Developmental Biology
  • Stem Cell Biology
  • Genomics

Background:

  • Human pluripotent stem cells (hPSCs) model early human development but their distinct states are poorly understood.
  • Molecular regulators of pluripotency and differentiation remain incompletely characterized.
  • Transposable elements (TEs) are increasingly recognized for their roles in genome regulation and cell state dynamics.

Purpose of the Study:

  • To develop a novel reporter system for real-time monitoring of hPSC states.
  • To identify molecular determinants governing transitions between naïve and primed pluripotency.
  • To uncover novel cell populations and regulatory mechanisms within hPSCs.

Main Methods:

  • Engineering hPSCs with dual fluorescent reporters for specific TEs (LTR5_Hs, MER51B).
  • Real-time tracking and isolation of hPSCs undergoing pluripotency state transitions.
  • Transcriptomic analysis to characterize cell populations and identify regulatory factors.

Main Results:

  • TEs serve as sensitive indicators of distinct hPSC states and pluripotency dynamics.
  • The dual reporter system accurately monitors transitions from naïve to primed pluripotency and differentiation.
  • A rare, metastable primed hPSC population with preimplantation embryo development signatures and DNA damage response was identified.
  • NSD1 and FUS were identified as crucial safeguards of primed pluripotency.

Conclusions:

  • Transposable elements provide a powerful tool for dissecting hPSC states and developmental trajectories.
  • The novel reporter system offers a more accurate readout of pluripotency compared to conventional methods.
  • Understanding TEs and associated factors like NSD1 and FUS is critical for controlling hPSC fate and applications in regenerative medicine and developmental studies.