| First Author | Chakravarthy H | Year | 2017 |
| Journal | Cell Metab | Volume | 25 |
| Issue | 3 | Pages | 622-634 |
| PubMed ID | 28215845 | Mgi Jnum | J:251955 |
| Mgi Id | MGI:6106991 | Doi | 10.1016/j.cmet.2017.01.009 |
| Citation | Chakravarthy H, et al. (2017) Converting Adult Pancreatic Islet alpha Cells into beta Cells by Targeting Both Dnmt1 and Arx. Cell Metab 25(3):622-634 |
| abstractText | Insulin-producing pancreatic beta cells in mice can slowly regenerate from glucagon-producing alpha cells in settings like beta cell loss, but the basis of this conversion is unknown. Moreover, it remains unclear if this intra-islet cell conversion is relevant to diseases like type 1 diabetes (T1D). We show that the alpha cell regulators Aristaless-related homeobox (Arx) and DNA methyltransferase 1 (Dnmt1) maintain alpha cell identity in mice. Within 3 months of Dnmt1 and Arx loss, lineage tracing and single-cell RNA sequencing revealed extensive alpha cell conversion into progeny resembling native beta cells. Physiological studies demonstrated that converted alpha cells acquire hallmark beta cell electrophysiology and show glucose-stimulated insulin secretion. In T1D patients, subsets of glucagon-expressing cells show loss of DNMT1 and ARX and produce insulin and other beta cell factors, suggesting that DNMT1 and ARX maintain alpha cell identity in humans. Our work reveals pathways regulated by Arx and Dnmt1 that are sufficient for achieving targeted generation of beta cells from adult pancreatic alpha cells. |
