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Updated: Mar 10, 2026

Single-cell Transcriptomic Analyses of Mouse Pancreatic Endocrine Cells
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The Chromatin Modifier MSK1/2 Suppresses Endocrine Cell Fates during Mouse Pancreatic Development

Neha Bhat1, Jeehye Park2, Huda Y Zoghbi2

  • 1Institute for Regenerative Medicine, Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Civic Center Blvd., Philadelphia, PA, United States of America.

Plos One
|December 16, 2016
PubMed

Insights

Scientists identified MSK1/2 kinases as key regulators of pancreatic cell development. Inhibiting these kinases promotes beta cell production, offering a potential new strategy for treating Type I diabetes.

Area of Science:

  • Developmental Biology
  • Molecular Biology
  • Endocrinology

Background:

  • Type I diabetes results from the loss of insulin-producing beta cells.
  • Identifying novel targets to enhance beta cell regeneration is crucial for diabetes treatment.

Purpose of the Study:

  • To discover pharmacologically-targetable histone-modifying proteins that boost beta cell production from pancreatic progenitors.
  • To investigate the role of histone modifications and their kinases in pancreatic cell fate determination.

Main Methods:

  • Performed a screen for histone modifications at key pancreatic genes induced by signal transduction pathways.
  • Investigated the temporal dynamics of serine-28 phosphorylated histone H3 (H3S28ph) and its kinases, MSK1 and MSK2 (MSK1/2).
  • Utilized pharmacological inhibition and germline knockout of MSK1/2 in embryonic pancreatic explants and models.

Main Results:

  • H3S28ph and MSK1/2 were found enriched at endocrine and acinar promoters in early pancreatic progenitors.
  • MSK1/2 inhibition in embryonic explants promoted endocrine cell specification, including beta cells, and reduced acinar cell fates.
  • Germline knockout of MSK1/2 enhanced alpha cells and reduced acinar differentiation; monoallelic loss of Msk1 increased beta cell mass.

Conclusions:

  • The screen of chromatin state dynamics identified MSK1/2 as regulators of pancreatic cell fate.
  • Pharmacological targeting of MSK1/2 shows potential for enhancing beta cell production and treating Type I diabetes.
  • This approach can be applied to other developmental contexts to modulate cell fates.

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