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NEUROD1 reinforces endocrine cell fate acquisition in pancreatic development

Author

Listed:
  • Romana Bohuslavova

    (Institute of Biotechnology CAS)

  • Valeria Fabriciova

    (Institute of Biotechnology CAS)

  • Ondrej Smolik

    (Institute of Biotechnology CAS)

  • Laura Lebrón-Mora

    (Institute of Biotechnology CAS)

  • Pavel Abaffy

    (Institute of Biotechnology CAS)

  • Sarka Benesova

    (Institute of Biotechnology CAS)

  • Daniel Zucha

    (Institute of Biotechnology CAS)

  • Lukas Valihrach

    (Institute of Biotechnology CAS)

  • Zuzana Berkova

    (Institute for Clinical and Experimental Medicine)

  • Frantisek Saudek

    (Institute for Clinical and Experimental Medicine)

  • Gabriela Pavlinkova

    (Institute of Biotechnology CAS)

Abstract

NEUROD1 is a transcription factor that helps maintain a mature phenotype of pancreatic β cells. Disruption of Neurod1 during pancreatic development causes severe neonatal diabetes; however, the exact role of NEUROD1 in the differentiation programs of endocrine cells is unknown. Here, we report a crucial role of the NEUROD1 regulatory network in endocrine lineage commitment and differentiation. Mechanistically, transcriptome and chromatin landscape analyses demonstrate that Neurod1 inactivation triggers a downregulation of endocrine differentiation transcription factors and upregulation of non-endocrine genes within the Neurod1-deficient endocrine cell population, disturbing endocrine identity acquisition. Neurod1 deficiency altered the H3K27me3 histone modification pattern in promoter regions of differentially expressed genes, which resulted in gene regulatory network changes in the differentiation pathway of endocrine cells, compromising endocrine cell potential, differentiation, and functional properties.

Suggested Citation

  • Romana Bohuslavova & Valeria Fabriciova & Ondrej Smolik & Laura Lebrón-Mora & Pavel Abaffy & Sarka Benesova & Daniel Zucha & Lukas Valihrach & Zuzana Berkova & Frantisek Saudek & Gabriela Pavlinkova, 2023. "NEUROD1 reinforces endocrine cell fate acquisition in pancreatic development," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-41306-6
    DOI: 10.1038/s41467-023-41306-6
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    References listed on IDEAS

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    2. Marissa A. Scavuzzo & Matthew C. Hill & Jolanta Chmielowiec & Diane Yang & Jessica Teaw & Kuanwei Sheng & Yuelin Kong & Maria Bettini & Chenghang Zong & James F. Martin & Malgorzata Borowiak, 2018. "Endocrine lineage biases arise in temporally distinct endocrine progenitors during pancreatic morphogenesis," Nature Communications, Nature, vol. 9(1), pages 1-21, December.
    3. Eiji Yoshihara & Carolyn O’Connor & Emanuel Gasser & Zong Wei & Tae Gyu Oh & Tiffany W. Tseng & Dan Wang & Fritz Cayabyab & Yang Dai & Ruth T. Yu & Christopher Liddle & Annette R. Atkins & Michael Dow, 2020. "Immune-evasive human islet-like organoids ameliorate diabetes," Nature, Nature, vol. 586(7830), pages 606-611, October.
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