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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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Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
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Alternative SET/TAFI Promoters Regulate Embryonic Stem Cell Differentiation.

Raghu Ram Edupuganti1, Arigela Harikumar1, Yair Aaronson1

  • 1The Department of Genetics, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Edmond J. Safra Campus, Jerusalem 91904, Israel.

Stem Cell Reports
|October 3, 2017
PubMed
Summary
This summary is machine-generated.

Researchers identified SET as a key regulator in embryonic stem cells (ESCs). SET controls pluripotency and differentiation via isoform switching, impacting cell proliferation and development.

Keywords:
SETTAF-ITAFIchromatindifferentiationembryonic stem cellsepigeneticshistone chaperonehistone dynamicspluripotency

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Area of Science:

  • Stem cell biology
  • Epigenetics
  • Molecular and developmental biology

Background:

  • Embryonic stem cells (ESCs) rely on transcription factors and chromatin regulators for pluripotency.
  • Identifying novel regulators is crucial for understanding stem cell dynamics.

Purpose of the Study:

  • To discover new regulators of pluripotency and differentiation in mouse ESCs.
  • To investigate the role of the identified regulator, SET, in stem cell maintenance and differentiation.

Main Methods:

  • Screening of fluorescent fusion protein libraries in mouse ESCs.
  • Analysis of fluorescence loss during differentiation to identify regulators.
  • Investigating SET isoform switching via alternative promoters (SETα and SETβ).
  • Assessing the impact of SET depletion on cellular functions and development.

Main Results:

  • Identification of SET as a regulator exhibiting an isoform shift (SETα to SETβ) during differentiation.
  • SETα is regulated by pluripotency factors.
  • SET depletion leads to reduced proliferation, impaired neuronal differentiation, and developmental arrest.
  • Photobleaching experiments revealed SET's role in maintaining dynamic chromatin states in ESCs.

Conclusions:

  • SET is a critical regulator of pluripotency and early differentiation in ESCs.
  • Alternative promoter usage controls SET's dynamic isoform switching.
  • SET plays a vital role in maintaining chromatin dynamics essential for stem cell function.