Single-cell transcriptomics of human islet ontogeny defines the molecular basis of ß-cell dedifferentiation in T2D.
Mol Metab
; 42: 101057, 2020 12.
Article
en En
| MEDLINE
| ID: mdl-32739450
ABSTRACT
OBJECTIVE:
Dedifferentiation of pancreatic ß-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 ß-cells during human ontogeny. We also compared islets from non-diabetic and T2D individuals.RESULTS:
Both α- and ß-cells mature in part by repressing non-endocrine genes; however, α-cells retain hallmarks of an immature state, while ß-cells attain a full ß-cell specific gene expression program. In islets from T2D donors, both α- and ß-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 ß-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.Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Diabetes Mellitus Tipo 2
/
Células Secretoras de Insulina
/
Desdiferenciación Celular
Tipo de estudio:
Risk_factors_studies
Límite:
Humans
Idioma:
En
Revista:
Mol Metab
Año:
2020
Tipo del documento:
Article
País de afiliación:
Israel