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

Marissa A. Scavuzzo, Matthew C. Hill, Jolanta Chmielowiec, Diane Yang, Jessica Teaw, Kuanwei Sheng, Yuelin Kong, Maria Bettini, Chenghang Zong, James F. Martin () and Malgorzata Borowiak ()
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Marissa A. Scavuzzo: Baylor College of Medicine
Matthew C. Hill: Baylor College of Medicine
Jolanta Chmielowiec: Baylor College of Medicine
Diane Yang: Baylor College of Medicine
Jessica Teaw: Baylor College of Medicine
Kuanwei Sheng: Baylor College of Medicine
Yuelin Kong: Baylor College of Medicine
Maria Bettini: Baylor College of Medicine
Chenghang Zong: Baylor College of Medicine
James F. Martin: Baylor College of Medicine
Malgorzata Borowiak: Baylor College of Medicine

Nature Communications, 2018, vol. 9, issue 1, 1-21

Abstract: 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.

Date: 2018
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-05740-1

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DOI: 10.1038/s41467-018-05740-1

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