| First Author | Sakhneny L | Year | 2021 |
| Journal | Dev Cell | Volume | 56 |
| Issue | 19 | Pages | 2703-2711.e5 |
| PubMed ID | 34499867 | Mgi Jnum | J:311943 |
| Mgi Id | MGI:6781671 | Doi | 10.1016/j.devcel.2021.08.014 |
| Citation | Sakhneny L, et al. (2021) The postnatal pancreatic microenvironment guides beta cell maturation through BMP4 production. Dev Cell 56(19):2703-2711.e5 |
| abstractText | Glucose homeostasis depends on regulated insulin secretion from pancreatic beta cells, which acquire their mature phenotype postnatally. The functional maturation of beta cells is regulated by a combination of cell-autonomous and exogenous factors; the identity of the latter is mostly unknown. Here, we identify BMP4 as a critical component through which the pancreatic microenvironment regulates beta cell function. By combining transgenic mouse models and human iPSCs, we show that BMP4 promotes the expression of core beta cell genes and is required for proper insulin production and secretion. We identified pericytes as the primary pancreatic source of BMP4, which start producing this ligand midway through the postnatal period, at the age beta cells mature. Overall, our findings show that the islet niche directly promotes beta cell functional maturation through the timely production of BMP4. Our study highlights the need to recapitulate the physiological postnatal islet niche for generating fully functional stem-cell-derived beta cells for cell replacement therapy for diabetes. |
