Histone deacetylase inhibitors modify pancreatic cell fate determination and amplify endocrine progenitors.

Molecular and Cellular Biology
Cécile HaumaitreRaphaël Scharfmann

Abstract

During pancreas development, transcription factors play critical roles in exocrine and endocrine differentiation. Transcriptional regulation in eukaryotes occurs within chromatin and is influenced by posttranslational histone modifications (e.g., acetylation) involving histone deacetylases (HDACs). Here, we show that HDAC expression and activity are developmentally regulated in the embryonic rat pancreas. We discovered that pancreatic treatment with different HDAC inhibitors (HDACi) modified the timing and determination of pancreatic cell fate. HDACi modified the exocrine lineage via abolition and enhancement of acinar and ductal differentiation, respectively. Importantly, HDACi treatment promoted the NGN3 proendocrine lineage, leading to an increased pool of endocrine progenitors and modified endocrine subtype lineage choices. Interestingly, treatments with trichostatin A and sodium butyrate, two inhibitors of both class I and class II HDACs, enhanced the pool of beta cells. These results highlight the roles of HDACs at key points in exocrine and endocrine differentiation. They show the powerful use of HDACi to switch pancreatic cell determination and amplify specific cellular subtypes, with potential applications in cell repl...Continue Reading

References

May 1, 1995·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·M YoshidaT Beppu
Jun 17, 1998·Genes & Development·M HebrokD A Melton
Oct 22, 1998·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·M H Kuo, C D Allis
Sep 7, 1999·Nature·A ApelqvistH Edlund
Mar 4, 2000·Proceedings of the National Academy of Sciences of the United States of America·G GradwohlF Guillemot
Apr 11, 2000·Molecular and Cellular Biology·H P HuangM J Tsai
May 29, 2000·Journal of Cellular Physiology·W D Cress, E Seto
Sep 5, 2001·Current Opinion in Genetics & Development·T A McKinseyE N Olson
Feb 16, 2002·Methods : a Companion to Methods in Enzymology·K J Livak, T D Schmittgen
Nov 14, 2002·The Biochemical Journal·Annemieke J M de RuijterAndré B P van Kuilenburg
Jul 4, 2003·The Journal of Nutrition·James R Davie
Jul 29, 2003·Diabetes·Bertrand DuvilliéRaphael Scharfmann
Sep 17, 2003·The Journal of Pharmacology and Experimental Therapeutics·Erding HuMichael Jaye
Oct 17, 2003·Genes & Development·Patrick CollombatPeter Gruss
Apr 3, 2004·Molecular and Cellular Biology·Liqiang TouRamesh A Shivdasani
Aug 26, 2004·Advances in Cancer Research·Paul A MarksWilliam Kevin Kelly
Nov 13, 2004·Proceedings of the National Academy of Sciences of the United States of America·Jenny HsiehFred H Gage
May 18, 2005·The Journal of Cell Biology·Siming ShenPatrizia Casaccia-Bonnefil
Jan 7, 2006·Circulation Research·Johannes Backs, Eric N Olson
Jan 7, 2006·Nature Reviews. Cancer·Saverio Minucci, Pier Giuseppe Pelicci
Jan 13, 2006·The Journal of Biological Chemistry·Eung Jae YooJae Bum Kim
Feb 14, 2006·Gastroenterology·Christophe E PierreuxFrédéric P Lemaigre
Mar 1, 2006·Diabetes·Bertrand DuvilliéRaphael Scharfmann
Mar 7, 2006·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Gamze KilicBeatriz Sosa-Pineda
May 27, 2006·Molecular Endocrinology·Hyun Woo LeeJae Bum Kim
Jul 11, 2006·Mechanisms of Development·Patrick CollombatAhmed Mansouri

❮ Previous
Next ❯

Citations

Jan 14, 2012·Cellular and Molecular Life Sciences : CMLS·Nuria C Bramswig, Klaus H Kaestner
Aug 3, 2013·Current Diabetes Reports·Cecile Haumaitre
Mar 6, 2010·The Proceedings of the Nutrition Society·L AttigC Junien
Jan 16, 2010·Cell Death and Differentiation·S Mora-CastillaF J Bedoya
Feb 16, 2011·Immunology and Cell Biology·Tejas PatelSundararajan Jayaraman
Mar 22, 2012·Proceedings of the National Academy of Sciences of the United States of America·Stefan KubicekStuart L Schreiber
Jul 10, 2009·The Journal of Biological Chemistry·Gaëlle FilhoulaudRaphaël Scharfmann
Sep 9, 2009·The Journal of Biological Chemistry·Taeko WadaYusuke Furukawa
Nov 3, 2011·Antioxidants & Redox Signaling·Junjun WangGuoyao Wu
Jul 3, 2009·Current Opinion in Gastroenterology·Sohail Husain, Edwin Thrower
May 14, 2010·American Journal of Physiology. Renal Physiology·Louisa M Villeneuve, Rama Natarajan
Jul 20, 2012·International Journal of Endocrinology·Amedeo Vetere, Bridget K Wagner
Aug 26, 2011·The Journal of Clinical Investigation·Philippe RavassardRaphael Scharfmann
Feb 26, 2013·The Journal of Clinical Investigation·Nuria C BramswigKlaus H Kaestner
Oct 26, 2010·Endocrine Reviews·Z HochbergK Albertsson-Wikland
Oct 2, 2009·Development·Renaud Desgraz, Pedro L Herrera
Dec 7, 2013·PloS One·Ersin AkinciJonathan M W Slack
Jan 29, 2011·Molecular Medicine·Dan P ChristensenThomas Mandrup-Poulsen
Nov 14, 2013·Cellular and Molecular Life Sciences : CMLS·David A CanoAnabel Rojas
May 9, 2014·Epigenomics·Bennett C Meier, Bridget K Wagner
Jul 23, 2011·Diabetes & Metabolism·A SoggiaB Duvillié
Sep 10, 2014·Journal of Endocrinological Investigation·Z-H TangK Zhang
Dec 29, 2013·Journal of Genetics·Zi-Hui TangLinuo Zhou
Mar 7, 2013·Cellular and Molecular Life Sciences : CMLS·Ionel SandoviciMiguel Constância
Jan 20, 2016·Trends in Endocrinology and Metabolism : TEM·Stephanie A Campbell, Brad G Hoffman
Dec 20, 2014·International Journal of Molecular Sciences·S Suresh KumarAkon Higuchi
Mar 20, 2012·Trends in Endocrinology and Metabolism : TEM·Nuria C Bramswig, Klaus H Kaestner
Apr 7, 2009·Cancer Letters·Oronza Antonietta BotrugnoSaverio Minucci
Dec 24, 2015·Best Practice & Research. Clinical Endocrinology & Metabolism·Evans Quilichini, Cécile Haumaitre
Jul 9, 2009·Biology of the Cell·Christopher A FrakerJuan Domínguez-Bendala
Jan 30, 2009·Journal of Cellular and Molecular Medicine·M W LawlessS G Gray
Feb 22, 2011·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Fong Cheng Pan, Chris Wright

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cell Fate Specification

Cell fate specification is determined by complex signal transduction pathways including Notch and the Sonic hedgehog signaling pathway. Here is the latest research on regulation of cell fate determination.