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Endocrine lineage biases arise in temporally distinct endocrine progenitors during pancreatic morphogenesis

Author

Listed:
  • Marissa A. Scavuzzo

    (Baylor College of Medicine)

  • Matthew C. Hill

    (Baylor College of Medicine)

  • Jolanta Chmielowiec

    (Baylor College of Medicine
    Baylor College of Medicine
    Baylor College of Medicine)

  • Diane Yang

    (Baylor College of Medicine)

  • Jessica Teaw

    (Baylor College of Medicine
    Baylor College of Medicine
    Baylor College of Medicine)

  • Kuanwei Sheng

    (Baylor College of Medicine
    Baylor College of Medicine
    Baylor College of Medicine)

  • Yuelin Kong

    (Baylor College of Medicine)

  • Maria Bettini

    (Baylor College of Medicine
    Baylor College of Medicine)

  • Chenghang Zong

    (Baylor College of Medicine
    Baylor College of Medicine
    Baylor College of Medicine)

  • James F. Martin

    (Baylor College of Medicine
    Baylor College of Medicine
    The Texas Heart Institute
    Baylor College of Medicine)

  • Malgorzata Borowiak

    (Baylor College of Medicine
    Baylor College of Medicine
    Baylor College of Medicine
    Baylor College of Medicine)

Abstract

Decoding the molecular composition of individual Ngn3 + endocrine progenitors (EPs) during pancreatic morphogenesis could provide insight into the mechanisms regulating hormonal cell fate. Here, we identify population markers and extensive cellular diversity including four EP subtypes reflecting EP maturation using high-resolution single-cell RNA-sequencing of the e14.5 and e16.5 mouse pancreas. While e14.5 and e16.5 EPs are constantly born and share select genes, these EPs are overall transcriptionally distinct concomitant with changes in the underlying epithelium. As a consequence, e16.5 EPs are not the same as e14.5 EPs: e16.5 EPs have a higher propensity to form beta cells. Analysis of e14.5 and e16.5 EP chromatin states reveals temporal shifts, with enrichment of beta cell motifs in accessible regions at later stages. Finally, we provide transcriptional maps outlining the route progenitors take as they make cell fate decisions, which can be applied to advance the in vitro generation of beta cells.

Suggested Citation

  • 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.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-05740-1
    DOI: 10.1038/s41467-018-05740-1
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    Cited by:

    1. Xiaochan Xu & Philip Allan Seymour & Kim Sneppen & Ala Trusina & Anuska la Rosa Egeskov-Madsen & Mette Christine Jørgensen & Mogens Høgh Jensen & Palle Serup, 2023. "Jag1-Notch cis-interaction determines cell fate segregation in pancreatic development," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    2. Jolanta Chmielowiec & Wojciech J. Szlachcic & Diane Yang & Marissa A. Scavuzzo & Katrina Wamble & Alejandro Sarrion-Perdigones & Omaima M. Sabek & Koen J. T. Venken & Malgorzata Borowiak, 2022. "Human pancreatic microenvironment promotes β-cell differentiation via non-canonical WNT5A/JNK and BMP signaling," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    3. 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.
    4. Teodora Manea & Jessica Kristine Nelson & Cristina Maria Garrone & Karin Hansson & Ian Evans & Axel Behrens & Rocio Sancho, 2023. "USP7 controls NGN3 stability and pancreatic endocrine lineage development," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    5. Zhuo Ma & Xiaofei Zhang & Wen Zhong & Hongyan Yi & Xiaowei Chen & Yinsuo Zhao & Yanlin Ma & Eli Song & Tao Xu, 2023. "Deciphering early human pancreas development at the single-cell level," Nature Communications, Nature, vol. 14(1), pages 1-17, December.

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