Other
15 Authors
- Banerjee A,
- Shao Q,
- Dadi PK,
- Hodges E,
- Hu R,
- Simmons AJ,
- Attalla J,
- Jacobson DA,
- Wang S,
- Lau KS,
- Herring CA,
- Gu G,
- Liu B,
- Liu J,
- Xu Y
| First Author | Liu J | Year | 2019 |
| Journal | Dev Cell | Volume | 48 |
| Issue | 1 | Pages | 49-63.e7 |
| PubMed ID | 30620902 | Mgi Jnum | J:272578 |
| Mgi Id | MGI:6284119 | Doi | 10.1016/j.devcel.2018.11.048 |
| Citation | Liu J, et al. (2019) Neurog3-Independent Methylation Is the Earliest Detectable Mark Distinguishing Pancreatic Progenitor Identity. Dev Cell 48(1):49-63.e7 |
| abstractText | In the developing pancreas, transient Neurog3-expressing progenitors give rise to four major islet cell types: alpha, beta, delta, and gamma; when and how the Neurog3(+) cells choose cell fate is unknown. Using single-cell RNA-seq, trajectory analysis, and combinatorial lineage tracing, we showed here that the Neurog3(+) cells co-expressing Myt1 (i.e., Myt1(+)Neurog3(+)) were biased toward beta cell fate, while those not simultaneously expressing Myt1 (Myt1(-)Neurog3(+)) favored alpha fate. Myt1 manipulation only marginally affected alpha versus beta cell specification, suggesting Myt1 as a marker but not determinant for islet-cell-type specification. The Myt1(+)Neurog3(+) cells displayed higher Dnmt1 expression and enhancer methylation at Arx, an alpha-fate-promoting gene. Inhibiting Dnmts in pancreatic progenitors promoted alpha cell specification, while Dnmt1 overexpression or Arx enhancer hypermethylation favored beta cell production. Moreover, the pancreatic progenitors contained distinct Arx enhancer methylation states without transcriptionally definable sub-populations, a phenotype independent of Neurog3 activity. These data suggest that Neurog3-independent methylation on fate-determining gene enhancers specifies distinct endocrine-cell programs. |
