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Title: HES6 reverses nuclear reprogramming of insulin-producing cells following cell fusion

Abstract

To examine the mechanism by which growth-stimulated pancreatic {beta}-cells dedifferentiate, somatic cell fusions were performed between MIN6, a highly differentiated mouse insulinoma, and {beta}lox5, a cell line derived from human {beta}-cells which progressively dedifferentiated in culture. MIN6/{beta}lox5 somatic cells hybrids underwent silencing of insulin expression and a marked decline in PDX1, NeuroD, and MafA, indicating that {beta}lox5 expresses a dominant transacting factor(s) that represses {beta}-cell differentiation. Expression of Hes1, which inhibits endocrine differentiation was higher in hybrid cells than in parental MIN6 cells. Hes6, a repressor of Hes1, was highly expressed in primary {beta}-cells as well as MIN6, but was repressed in hybrids. Hes6 overexpression using a retroviral vector led to a decrease in Hes1 levels, an increase in {beta}-cell transcription factors and partial restoration of insulin expression. We conclude that the balance of Notch activators and inhibitors may play an important role in maintaining the {beta}-cell differentiated state.

Authors:
 [1];  [1];  [1];  [2];  [1];  [2];  [1];  [2];
  1. UCSD Department of Pediatrics, 9500 Gilman Drive, La Jolla, CA 92093-0816 (United States)
  2. (United States)
Publication Date:
OSTI Identifier:
20979866
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 355; Journal Issue: 2; Other Information: DOI: 10.1016/j.bbrc.2007.01.153; PII: S0006-291X(07)00205-7; Copyright (c) 2007 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ANIMAL GROWTH; BIOLOGICAL RECOVERY; CELL DIFFERENTIATION; HYBRIDIZATION; INSULIN; MICE; PANCREAS; SOMATIC CELLS; TRANSCRIPTION FACTORS

Citation Formats

Ball, Andrew J., Abrahamsson, Annelie E., Tyrberg, Bjoern, Burnham Institute for Medical Research, Itkin-Ansari, Pamela, Burnham Institute for Medical Research, Levine, Fred, Burnham Institute for Medical Research, and E-mail: flevine@ucsd.edu. HES6 reverses nuclear reprogramming of insulin-producing cells following cell fusion. United States: N. p., 2007. Web. doi:10.1016/j.bbrc.2007.01.153.
Ball, Andrew J., Abrahamsson, Annelie E., Tyrberg, Bjoern, Burnham Institute for Medical Research, Itkin-Ansari, Pamela, Burnham Institute for Medical Research, Levine, Fred, Burnham Institute for Medical Research, & E-mail: flevine@ucsd.edu. HES6 reverses nuclear reprogramming of insulin-producing cells following cell fusion. United States. doi:10.1016/j.bbrc.2007.01.153.
Ball, Andrew J., Abrahamsson, Annelie E., Tyrberg, Bjoern, Burnham Institute for Medical Research, Itkin-Ansari, Pamela, Burnham Institute for Medical Research, Levine, Fred, Burnham Institute for Medical Research, and E-mail: flevine@ucsd.edu. Fri . "HES6 reverses nuclear reprogramming of insulin-producing cells following cell fusion". United States. doi:10.1016/j.bbrc.2007.01.153.
@article{osti_20979866,
title = {HES6 reverses nuclear reprogramming of insulin-producing cells following cell fusion},
author = {Ball, Andrew J. and Abrahamsson, Annelie E. and Tyrberg, Bjoern and Burnham Institute for Medical Research and Itkin-Ansari, Pamela and Burnham Institute for Medical Research and Levine, Fred and Burnham Institute for Medical Research and E-mail: flevine@ucsd.edu},
abstractNote = {To examine the mechanism by which growth-stimulated pancreatic {beta}-cells dedifferentiate, somatic cell fusions were performed between MIN6, a highly differentiated mouse insulinoma, and {beta}lox5, a cell line derived from human {beta}-cells which progressively dedifferentiated in culture. MIN6/{beta}lox5 somatic cells hybrids underwent silencing of insulin expression and a marked decline in PDX1, NeuroD, and MafA, indicating that {beta}lox5 expresses a dominant transacting factor(s) that represses {beta}-cell differentiation. Expression of Hes1, which inhibits endocrine differentiation was higher in hybrid cells than in parental MIN6 cells. Hes6, a repressor of Hes1, was highly expressed in primary {beta}-cells as well as MIN6, but was repressed in hybrids. Hes6 overexpression using a retroviral vector led to a decrease in Hes1 levels, an increase in {beta}-cell transcription factors and partial restoration of insulin expression. We conclude that the balance of Notch activators and inhibitors may play an important role in maintaining the {beta}-cell differentiated state.},
doi = {10.1016/j.bbrc.2007.01.153},
journal = {Biochemical and Biophysical Research Communications},
number = 2,
volume = 355,
place = {United States},
year = {Fri Apr 06 00:00:00 EDT 2007},
month = {Fri Apr 06 00:00:00 EDT 2007}
}