Transcriptional Heterogeneity of Beta Cells in the Intact Pancreas.
Dev Cell
; 48(1): 115-125.e4, 2019 01 07.
Article
in En
| MEDLINE
| ID: mdl-30503750
ABSTRACT
Pancreatic beta cells have been shown to be heterogeneous at multiple levels. However, spatially interrogating transcriptional heterogeneity in the intact tissue has been challenging. Here, we developed an optimized protocol for single-molecule transcript imaging in the intact pancreas and used it to identify a sub-population of "extreme" beta cells with elevated mRNA levels of insulin and other secretory genes. Extreme beta cells contain higher ribosomal and proinsulin content but lower levels of insulin protein in fasted states, suggesting they may be tuned for basal insulin secretion. They exhibit a distinctive intra-cellular polarization pattern, with elevated mRNA concentrations in an apical ER-enriched compartment, distinct from the localization of nascent and mature proteins. The proportion of extreme cells increases in db/db diabetic mice, potentially facilitating the required increase in basal insulin. Our results thus highlight a sub-population of beta cells that may carry distinct functional roles along physiological and pathological timescales.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Pancreas
/
Islets of Langerhans
/
Genetic Heterogeneity
/
Insulin-Secreting Cells
Limits:
Animals
Language:
En
Journal:
Dev Cell
Journal subject:
EMBRIOLOGIA
Year:
2019
Document type:
Article
Affiliation country:
Israel