Retinoic acid signaling within pancreatic endocrine progenitors regulates mouse and human β cell specification | Zendy

David S. Lorberbaum | Zendy; Siddharth Kishore | Zendy; Carolina Rosselot | Zendy; Dylan Sarbaugh | Zendy; Elliott P. Brooks | Zendy; Eloise Aragon | Zendy; Shouhong Xuan | Zendy; Olivier Simon | Zendy; Debashis Ghosh | Zendy; Cathy Mendelsohn | Zendy; Paul Gadue | Zendy; Lori Sussel | Zendy

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Retinoic acid signaling within pancreatic endocrine progenitors regulates mouse and human β cell specification

Author(s) -

David S. Lorberbaum,

Siddharth Kishore,

Carolina Rosselot,

Dylan Sarbaugh,

Elliott P. Brooks,

Eloise Aragon,

Shouhong Xuan,

Olivier Simon,

Debashis Ghosh,

Cathy Mendelsohn,

Paul Gadue,

Lori Sussel

Publication year - 2020

Publication title -

development

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 3.754

H-Index - 325

eISSN - 1477-9129

pISSN - 0950-1991

DOI - 10.1242/dev.189977

Subject(s) - biology , wnt signaling pathway , progenitor cell , microbiology and biotechnology , retinoic acid , enteroendocrine cell , signal transduction , pancreas , endocrine system , cellular differentiation , progenitor , ectopic expression , stem cell , endocrinology , medicine , genetics , hormone , cell culture , gene

Retinoic acid (RA) signaling is essential for multiple developmental processes, including appropriate pancreas formation from the foregut endoderm. RA is also required to generate pancreatic progenitors from human pluripotent stem cells. However, the role of RA signaling during endocrine specification has not been fully explored. In this study, we demonstrate that the disruption of RA signaling within the NEUROG3-expressing endocrine progenitor population impairs mouse β cell differentiation and induces ectopic expression of crucial δ cell genes, including somatostatin. In addition, the inhibition of the RA pathway in hESC-derived pancreatic progenitors downstream of NEUROG3 induction impairs insulin expression. We further determine that RA-mediated regulation of endocrine cell differentiation occurs through Wnt pathway components. Together, these data demonstrate the importance of RA signaling in endocrine specification and identify conserved mechanisms by which RA signaling directs pancreatic endocrine cell fate.

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