Macrophage/epithelium cross-talk regulates cell cycle progression and migration in pancreatic progenitors.

Macrophages populate the mesenchymal compartment of all organs during embryogenesis and have been shown to support tissue organogenesis and regeneration by regulating remodeling of the extracellular microenvironment. Whether this mesenchymal component can also dictate select developmental decisions...

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Autores principales:	Kristin Mussar, Andrew Tucker, Linsey McLennan, Addie Gearhart, Antonio J Jimenez-Caliani, Vincenzo Cirulli, Laura Crisa
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a8d06ce5f7c04b53a326167cc4c51f16
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spelling	oai:doaj.org-article:a8d06ce5f7c04b53a326167cc4c51f162021-11-18T08:31:54ZMacrophage/epithelium cross-talk regulates cell cycle progression and migration in pancreatic progenitors.1932-620310.1371/journal.pone.0089492https://doaj.org/article/a8d06ce5f7c04b53a326167cc4c51f162014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24586821/?tool=EBIhttps://doaj.org/toc/1932-6203Macrophages populate the mesenchymal compartment of all organs during embryogenesis and have been shown to support tissue organogenesis and regeneration by regulating remodeling of the extracellular microenvironment. Whether this mesenchymal component can also dictate select developmental decisions in epithelia is unknown. Here, using the embryonic pancreatic epithelium as model system, we show that macrophages drive the epithelium to execute two developmentally important choices, i.e. the exit from cell cycle and the acquisition of a migratory phenotype. We demonstrate that these developmental decisions are effectively imparted by macrophages activated toward an M2 fetal-like functional state, and involve modulation of the adhesion receptor NCAM and an uncommon "paired-less" isoform of the transcription factor PAX6 in the epithelium. Over-expression of this PAX6 variant in pancreatic epithelia controls both cell motility and cell cycle progression in a gene-dosage dependent fashion. Importantly, induction of these phenotypes in embryonic pancreatic transplants by M2 macrophages in vivo is associated with an increased frequency of endocrine-committed cells emerging from ductal progenitor pools. These results identify M2 macrophages as key effectors capable of coordinating epithelial cell cycle withdrawal and cell migration, two events critical to pancreatic progenitors' delamination and progression toward their differentiated fates.Kristin MussarAndrew TuckerLinsey McLennanAddie GearhartAntonio J Jimenez-CalianiVincenzo CirulliLaura CrisaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 2, p e89492 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Kristin Mussar Andrew Tucker Linsey McLennan Addie Gearhart Antonio J Jimenez-Caliani Vincenzo Cirulli Laura Crisa Macrophage/epithelium cross-talk regulates cell cycle progression and migration in pancreatic progenitors.
description	Macrophages populate the mesenchymal compartment of all organs during embryogenesis and have been shown to support tissue organogenesis and regeneration by regulating remodeling of the extracellular microenvironment. Whether this mesenchymal component can also dictate select developmental decisions in epithelia is unknown. Here, using the embryonic pancreatic epithelium as model system, we show that macrophages drive the epithelium to execute two developmentally important choices, i.e. the exit from cell cycle and the acquisition of a migratory phenotype. We demonstrate that these developmental decisions are effectively imparted by macrophages activated toward an M2 fetal-like functional state, and involve modulation of the adhesion receptor NCAM and an uncommon "paired-less" isoform of the transcription factor PAX6 in the epithelium. Over-expression of this PAX6 variant in pancreatic epithelia controls both cell motility and cell cycle progression in a gene-dosage dependent fashion. Importantly, induction of these phenotypes in embryonic pancreatic transplants by M2 macrophages in vivo is associated with an increased frequency of endocrine-committed cells emerging from ductal progenitor pools. These results identify M2 macrophages as key effectors capable of coordinating epithelial cell cycle withdrawal and cell migration, two events critical to pancreatic progenitors' delamination and progression toward their differentiated fates.
format	article
author	Kristin Mussar Andrew Tucker Linsey McLennan Addie Gearhart Antonio J Jimenez-Caliani Vincenzo Cirulli Laura Crisa
author_facet	Kristin Mussar Andrew Tucker Linsey McLennan Addie Gearhart Antonio J Jimenez-Caliani Vincenzo Cirulli Laura Crisa
author_sort	Kristin Mussar
title	Macrophage/epithelium cross-talk regulates cell cycle progression and migration in pancreatic progenitors.
title_short	Macrophage/epithelium cross-talk regulates cell cycle progression and migration in pancreatic progenitors.
title_full	Macrophage/epithelium cross-talk regulates cell cycle progression and migration in pancreatic progenitors.
title_fullStr	Macrophage/epithelium cross-talk regulates cell cycle progression and migration in pancreatic progenitors.
title_full_unstemmed	Macrophage/epithelium cross-talk regulates cell cycle progression and migration in pancreatic progenitors.
title_sort	macrophage/epithelium cross-talk regulates cell cycle progression and migration in pancreatic progenitors.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/a8d06ce5f7c04b53a326167cc4c51f16
work_keys_str_mv	AT kristinmussar macrophageepitheliumcrosstalkregulatescellcycleprogressionandmigrationinpancreaticprogenitors AT andrewtucker macrophageepitheliumcrosstalkregulatescellcycleprogressionandmigrationinpancreaticprogenitors AT linseymclennan macrophageepitheliumcrosstalkregulatescellcycleprogressionandmigrationinpancreaticprogenitors AT addiegearhart macrophageepitheliumcrosstalkregulatescellcycleprogressionandmigrationinpancreaticprogenitors AT antoniojjimenezcaliani macrophageepitheliumcrosstalkregulatescellcycleprogressionandmigrationinpancreaticprogenitors AT vincenzocirulli macrophageepitheliumcrosstalkregulatescellcycleprogressionandmigrationinpancreaticprogenitors AT lauracrisa macrophageepitheliumcrosstalkregulatescellcycleprogressionandmigrationinpancreaticprogenitors
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Macrophage/epithelium cross-talk regulates cell cycle progression and migration in pancreatic progenitors.

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