Transcriptional Heterogeneity of Beta Cells in the Intact Pancreas.

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.

journal_name

Dev Cell

journal_title

Developmental cell

authors

Farack L,Golan M,Egozi A,Dezorella N,Bahar Halpern K,Ben-Moshe S,Garzilli I,Tóth B,Roitman L,Krizhanovsky V,Itzkovitz S

doi

10.1016/j.devcel.2018.11.001

subject

Has Abstract

pub_date

2019-01-07 00:00:00

pages

115-125.e4

issue

1

eissn

1534-5807

issn

1878-1551

pii

S1534-5807(18)30919-5

journal_volume

48

pub_type

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