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Kleiber T, Davidson G, Mengus G, et al. Single cell transcriptomics reveal trans-differentiation of pancreatic beta cells following inactivation of the TFIID subunit Taf4. Cell Death Dis. 2021;12(8):790doi: 10.1038/s41419-021-04067-y.
Kleiber, T., Davidson, G., Mengus, G., Martianov, I., & Davidson, I. (2021). Single cell transcriptomics reveal trans-differentiation of pancreatic beta cells following inactivation of the TFIID subunit Taf4. Cell death & disease, 12(8), 790. https://doi.org/10.1038/s41419-021-04067-y
Kleiber, Thomas, et al. "Single cell transcriptomics reveal trans-differentiation of pancreatic beta cells following inactivation of the TFIID subunit Taf4." Cell death & disease vol. 12,8 (2021): 790. doi: https://doi.org/10.1038/s41419-021-04067-y
Kleiber T, Davidson G, Mengus G, Martianov I, Davidson I. Single cell transcriptomics reveal trans-differentiation of pancreatic beta cells following inactivation of the TFIID subunit Taf4. Cell Death Dis. 2021 Aug 12;12(8):790. doi: 10.1038/s41419-021-04067-y. PMID: 34385420; PMCID: PMC8361202.
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Cell Death Dis. 2021 Aug 12;12(8):790. doi: 10.1038/s41419-021-04067-y.

Single cell transcriptomics reveal trans-differentiation of pancreatic beta cells following inactivation of the TFIID subunit Taf4.

Cell death & disease

Thomas Kleiber, Guillaume Davidson, Gabrielle Mengus, Igor Martianov, Irwin Davidson

Affiliations

  1. Institut de Génétique et de Biologie Moléculaire et Cellulaire. BP 163, 67404 Illkirch Cedex, C.U, Strasbourg, France.
  2. Centre National de la Recherche Scientifique, UMR7104, Illkirch, France.
  3. Institut National de la Santé et de la Recherche Médicale, U1258, Illkirch, France.
  4. Université de Strasbourg, Illkirch, France.
  5. Orphazyme, Ole Malloes Vej 3, 2200, Copenhagen, Danmark.
  6. Institut de Génétique et de Biologie Moléculaire et Cellulaire. BP 163, 67404 Illkirch Cedex, C.U, Strasbourg, France. [email protected].
  7. Centre National de la Recherche Scientifique, UMR7104, Illkirch, France. [email protected].
  8. Institut National de la Santé et de la Recherche Médicale, U1258, Illkirch, France. [email protected].
  9. Université de Strasbourg, Illkirch, France. [email protected].
  10. Equipe Labélisée Ligue National contre le Cancer, Alsace, France. [email protected].

PMID: 34385420 PMCID: PMC8361202 DOI: 10.1038/s41419-021-04067-y

Abstract

Regulation of gene expression involves a complex and dynamic dialogue between transcription factors, chromatin remodelling and modification complexes and the basal transcription machinery. To address the function of the Taf4 subunit of general transcription factor TFIID in the regulation of insulin signalling, it was inactivated in adult murine pancreatic beta cells. Taf4 inactivation impacted the expression of critical genes involved in beta-cell function leading to increased glycaemia, lowered plasma insulin levels and defective glucose-stimulated insulin secretion. One week after Taf4-loss, single-cell RNA-seq revealed cells with mixed beta cell, alpha and/or delta cell identities as well as a beta cell population trans-differentiating into alpha-like cells. Computational analysis of single-cell RNA-seq defines how known critical beta cell and alpha cell determinants may act in combination with additional transcription factors and the NuRF chromatin remodelling complex to promote beta cell trans-differentiation.

© 2021. The Author(s).

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