| First Author | Lu P | Year | 2024 |
| Journal | Cell Rep | Volume | 43 |
| Issue | 2 | Pages | 113703 |
| PubMed ID | 38265933 | Mgi Jnum | J:346058 |
| Mgi Id | MGI:7613987 | Doi | 10.1016/j.celrep.2024.113703 |
| Citation | Lu P, et al. (2024) Spatiotemporal role of SETD2-H3K36me3 in murine pancreatic organogenesis. Cell Rep 43(2):113703 |
| abstractText | Pancreas development is tightly controlled by multilayer mechanisms. Despite years of effort, large gaps remain in understanding how histone modifications coordinate pancreas development. SETD2, a predominant histone methyltransferase of H3K36me3, plays a key role in embryonic stem cell differentiation, whose role in organogenesis remains elusive. Here, by combination of cleavage under targets and tagmentation (CUT&Tag), assay for transposase-accessible chromatin using sequencing (ATAC-seq), and bulk RNA sequencing, we show a dramatic increase in the H3K36me3 level from the secondary transition phase and decipher the related transcriptional alteration. Using single-cell RNA sequencing, we define that pancreatic deletion of Setd2 results in abnormalities in both exocrine and endocrine lineages: hyperproliferative tip progenitor cells lead to abnormal differentiation; Ngn3(+) endocrine progenitors decline due to the downregulation of Nkx2.2, leading to insufficient endocrine development. Thus, these data identify SETD2 as a crucial player in embryonic pancreas development, providing a clue to understanding the dysregulation of histone modifications in pancreatic disorders. |
