Title | Endothelial cells control pancreatic cell fate at defined stages through EGFL7 signaling. |
Publication Type | Journal Article |
Year of Publication | 2015 |
Authors | Kao D-I, Lacko LA, Ding B-S, Huang C, Phung K, Gu G, Rafii S, Stuhlmann H, Chen S |
Journal | Stem Cell Reports |
Volume | 4 |
Issue | 2 |
Pagination | 181-9 |
Date Published | 2015 Feb 10 |
ISSN | 2213-6711 |
Keywords | Calcium-Binding Proteins, Cell Communication, Cell Differentiation, Cell Line, Cell Proliferation, Coculture Techniques, EGF Family of Proteins, Embryonic Stem Cells, Endothelial Cells, Endothelial Growth Factors, Gene Expression, Gene Expression Profiling, Gene Expression Regulation, Developmental, Homeodomain Proteins, Humans, Immunophenotyping, Pancreas, Phenotype, Signal Transduction, Stem Cell Niche, Trans-Activators, Transcriptome |
Abstract | <p>Although endothelial cells have been shown to affect mouse pancreatic development, their precise function in human development remains unclear. Using a coculture system containing human embryonic stem cell (hESC)-derived progenitors and endothelial cells, we found that endothelial cells play a stage-dependent role in pancreatic development, in which they maintain pancreatic progenitor (PP) self-renewal and impair further differentiation into hormone-expressing cells. The mechanistic studies suggest that the endothelial cells act through the secretion of EGFL7. Consistently, endothelial overexpression of EGFL7 in vivo using a transgenic mouse model resulted in an increase of PP proliferation rate and a decrease of differentiation toward endocrine cells. These studies not only identified the role of EGFL7 as the molecular handle involved in the crosstalk between endothelium and pancreatic epithelium, but also provide a paradigm for using hESC stepwise differentiation to dissect the stage-dependent roles of signals controlling organogenesis.</p> |
DOI | 10.1016/j.stemcr.2014.12.008 |
Alternate Journal | Stem Cell Reports |
PubMed ID | 25601205 |
PubMed Central ID | PMC4325230 |
Grant List | P30 DK058404 / DK / NIDDK NIH HHS / United States R01 DK065949 / DK / NIDDK NIH HHS / United States DP2 DK098093 / DK / NIDDK NIH HHS / United States / / Howard Hughes Medical Institute / United States R01 HL0820898 / HL / NHLBI NIH HHS / United States R01 HL082098 / HL / NHLBI NIH HHS / United States T32 HD060600 / HD / NICHD NIH HHS / United States |