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Regulation of pancreatic islet cell fates
Author(s) -
Sussel Lori
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.240.2
Subject(s) - biology , enteroendocrine cell , islet , pancreas , gene , embryonic stem cell , cell fate determination , beta cell , microbiology and biotechnology , cellular differentiation , cell , endocrine system , organogenesis , transcription factor , genetics , endocrinology , hormone , insulin
The regulation of lineage specification is a challenging problem in organogenesis. Our studies are focused on identifying the gene regulatory networks underlying cell fate decisions in the pancreas, with an emphasis on the endocrine islet cell lineages. To this end, we have identified a number of coding and non‐coding genes that are essential for the specification of islet cell fates. In particular, Nkx2.2 is an essential transcriptional regulatory protein that is important for the formation and function of several islet cell lineages. Furthermore, Nkx2.2 continues to be essential for the active maintenance of both beta cell identity and function in the adult. Deletion of Nkx2.2 in mature beta cells caused these cells to acquire non‐beta cell endocrine features resulting in populations of reprogrammed cells. These studies demonstrate that Nkx2.2 is a conserved master regulatory protein that controls the acquisition and maintenance of beta cell identity by directly activating critical beta cell genes and actively repressing genes that specify the alternative islet endocrine cell lineages. These studies have been instrumental in understanding normal pancreatic cell differentiation processes during embryonic development and underscored the need to continually maintain these cell specific gene regulatory programs in the adult organ. Our findings have also demonstrated the existence of remarkable plasticity in adult pancreatic lineages. Support or Funding Information NIH R01 DK082590 This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .