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Single-cell transcriptomics of human islet ontogeny defines the molecular basis of β-cell dedifferentiation in T2D.

Abstract：

OBJECTIVE:Dedifferentiation of pancreatic β-cells may reduce islet function in type 2 diabetes (T2D). However, the prevalence, plasticity and functional consequences of this cellular state remain unknown. METHODS:We employed single-cell RNAseq to detail the maturation program of α- and β-cells during human ontogeny. We also compared islets from non-diabetic and T2D individuals. RESULTS:Both α- and β-cells mature in part by repressing non-endocrine genes; however, α-cells retain hallmarks of an immature state, while β-cells attain a full β-cell specific gene expression program. In islets from T2D donors, both α- and β-cells have a less mature expression profile, de-repressing the juvenile genetic program and exocrine genes and increasing expression of exocytosis, inflammation and stress response signalling pathways. These changes are consistent with the increased proportion of β-cells displaying suboptimal function observed in T2D islets. CONCLUSIONS:These findings provide new insights into the molecular program underlying islet cell maturation during human ontogeny and the loss of transcriptomic maturity that occurs in islets of type 2 diabetics.

journal_name

Mol Metab

journal_title

Molecular metabolism

authors

Avrahami D,Wang YJ,Schug J,Feleke E,Gao L,Liu C,HPAP Consortium.,Naji A,Glaser B,Kaestner KH

doi

10.1016/j.molmet.2020.101057

subject

Has Abstract

pub_date

2020-12-01 00:00:00

pages

101057

issn

2212-8778

pii

S2212-8778(20)30131-9

journal_volume

42

pub_type

杂志文章

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