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Cited by 54Pancreatic function and diabetesDevelopmental Biology and Gene RegulationPancreatic and Hepatic Oncology Research

A Specialized Niche in the Pancreatic Microenvironment Promotes Endocrine Differentiation

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Cozzitorto, Corinna, Mueller, Laura, Ruzittu, Silvia, Mah, Nancy, Willnow, David, Darrigrand, Jean-Francois, Wilson, Heather, Khosravinia, Daniel +4 more·2020·Developmental Cell
DOI 10.1016/j.devcel.2020.08.003PMC PMC7720791
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Abstract

The interplay between pancreatic epithelium and the surrounding microenvironment is pivotal for pancreas formation and differentiation as well as adult organ homeostasis. The mesenchyme is the main component of the embryonic pancreatic microenvironment, yet its cellular identity is broadly defined, and whether it comprises functionally distinct cell subsets is not known. Using genetic lineage tracing, transcriptome, and functional studies, we identified mesenchymal populations with different roles during pancreatic development. Moreover, we showed that Pbx transcription factors act within the mouse pancreatic mesenchyme to define a pro-endocrine specialized niche. Pbx directs differentiation of endocrine progenitors into insulin- and glucagon-positive cells through non-cell-autonomous regulation of ECM-integrin interactions and soluble molecules. Next, we measured functional conservation between mouse and human pancreatic mesenchyme by testing identified mesenchymal factors in an iPSC-based differentiation model. Our findings provide insights into how lineage-specific crosstalk between epithelium and neighboring mesenchymal cells underpin the generation of different pancreatic cell types.

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Cited by

Sorted by citations

Authors
Cozzitorto, C., Mueller, L., Ruzittu, S., Mah, N., Willnow, D., Darrigrand, J.-F., Wilson, H., Khosravinia, D., Mahmoud, A.-A., Risolino, M., Selleri, L., & Spagnoli, F. M.
Affiliations
  • University of California, San Francisco (US)
  • King's College London (GB)
  • Charité – Universitätsmedizin Berlin (DE)
Corresponding author
Spagnoli, Francesca M.
ORCID
Venue
Developmental Cell
Publisher
Elsevier BV
Published
2020-10
Volume
55
Issue
2
Pages
150-162.e6
ISSN
1534-5807 (ISSN-L)
DOI
10.1016/j.devcel.2020.08.003
PMC
PMC7720791
OpenAlex
W3080447055
Cited by
54
References
0
Citations by year
2026: 8 · 2025: 8 · 2024: 7 · 2023: 7 · 2022: 9 · 2021: 14 · 2020: 1
FWCI
7.08
Type
journal article
Language
en
Open access
Licence
Locations
  • Developmental Cell (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • MDC Repository (Max-Delbrueck-Center for Molecular Medicine) (submittedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
  • Research Portal (King's College London) (submittedVersion, cc-by-nc-nd)
Funders
  • National Institutes of Health (R01 HD061403)
  • European Research Council (EFSD /AZ, 641036)
  • Juvenile Diabetes Research Foundation United States of America (1-INO-2018-634-A-N)
  • H2020 Future and Emerging Technologies (800981)
  • European Commission
  • Horizon 2020
  • Helmholtz Association
  • Horizon 2020 Framework Programme
Topics
  • Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
  • Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
Keywords
endocrine differentiation, endocrine progenitors, insulin, glucagon, non-cell-autonomous regulation, pancreatic development, iPSC differentiation
MeSH terms
Animals, Cell Differentiation, Endocrine System, Epithelium, Humans, Mesoderm, Mice, Transgenic, Pancreas, Gene Expression Regulation, Developmental, Organogenesis, Mesenchymal Stem Cells

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