TY - JOUR
T1 - Transcriptional Heterogeneity of Beta Cells in the Intact Pancreas
AU - Farack, Lydia
AU - Golan, Matan
AU - Egozi, Adi
AU - Dezorella, Nili
AU - Halpern, Keren Bahar
AU - Ben-Moshe, Shani
AU - Garzilli, Immacolata
AU - Toth, Beata
AU - Roitman, Lior
AU - Krizhanovsky, Valery
AU - Itzkovitz, Shalev
N1 - We thank Yuval Dor and Michael Walker for valuable comments. Electron microscopy studies were conducted at the Irving and Cherna Moskowitz Center for Nano and Bio-Nano Imaging at the Weizmann Institute of Science. We thank Hagit Shapiro and Eran Elinav for the B6.BKS(D)-Leprdb/J mice. S.I. is supported by the Henry Chanoch Krenter Institute for Biomedical Imaging and Genomics, The Leir Charitable Foundations, Richard Jakubskind Laboratory of Systems Biology, Cymerman-Jakubskind Prize, The Lord Sieff of Brimpton Memorial Fund, the I-CORE program of the Planning and Budgeting Committee and the Israel Science Foundation (grants 1902/12 and 1796/12), the Israel Science Foundation grant No. 1486/16, the EMBO Young Investigator Program and the European Research Council under the European Union’s Seventh Framework Programme (FP7/2007-2013)/ERC grant agreement number 335122, the Bert L. and N. Kuggie Vallee Foundation, and the Howard Hughes Medical Institute (HHMI) international research scholar award.
PY - 2019/1/7
Y1 - 2019/1/7
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85059604255&partnerID=8YFLogxK
U2 - 10.1016/j.devcel.2018.11.001
DO - 10.1016/j.devcel.2018.11.001
M3 - مقالة
SN - 1534-5807
VL - 48
SP - 115
EP - 125
JO - Developmental Cell
JF - Developmental Cell
IS - 1
ER -