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 Celljournal_title
Developmental cellauthors
Farack L,Golan M,Egozi A,Dezorella N,Bahar Halpern K,Ben-Moshe S,Garzilli I,Tóth B,Roitman L,Krizhanovsky V,Itzkovitz Sdoi
10.1016/j.devcel.2018.11.001subject
Has Abstractpub_date
2019-01-07 00:00:00pages
115-125.e4issue
1eissn
1534-5807issn
1878-1551pii
S1534-5807(18)30919-5journal_volume
48pub_type
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