Neurog3-Independent Methylation Is the Earliest Detectable Mark Distinguishing Pancreatic Progenitor Identity.

ABSTRACT: In the developing pancreas, transient Neurog3-expressing progenitors give rise to four major islet cell types: α, β, δ, and γ; 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 β cell fate, while those not simultaneously expressing Myt1 (Myt1^-Neurog3⁺) favored α fate. Myt1 manipulation only marginally affected α versus β 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

SUBMITTER: Liu J 

PROVIDER: S-EPMC6327977 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature