Prep1 (pKnox1) regulates mouse embryonic HSC cycling and self-renewal affecting the Stat1-Sca1 IFN-dependent pathway.

A hypomorphic Prep1 mutation results in embryonic lethality at late gestation with a pleiotropic embryonic phenotype that includes defects in all hematopoietic lineages. Reduced functionality of the hematopoietic stem cells (HSCs) compartment might be responsible for the hematopoietic phenotype obse...

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Autores principales:	Livia Modica, Giorgio Iotti, Annalisa D'Avola, Francesco Blasi
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/4da127b24861473b9c5b09af932efbfa
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spelling	oai:doaj.org-article:4da127b24861473b9c5b09af932efbfa2021-11-25T06:00:07ZPrep1 (pKnox1) regulates mouse embryonic HSC cycling and self-renewal affecting the Stat1-Sca1 IFN-dependent pathway.1932-620310.1371/journal.pone.0107916https://doaj.org/article/4da127b24861473b9c5b09af932efbfa2014-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0107916https://doaj.org/toc/1932-6203A hypomorphic Prep1 mutation results in embryonic lethality at late gestation with a pleiotropic embryonic phenotype that includes defects in all hematopoietic lineages. Reduced functionality of the hematopoietic stem cells (HSCs) compartment might be responsible for the hematopoietic phenotype observed at mid-gestation. In this paper we demonstrate that Prep1 regulates the number of HSCs in fetal livers (FLs), their clonogenic potential and their ability to de novo generate the hematopoietic system in ablated hosts. Furthermore, we show that Prep1 controls the self-renewal ability of the FL HSC compartment as demonstrated by serial transplantation experiments. The premature exhaustion of Prep1 mutant HSCs correlates with the reduced quiescent stem cell pool thus suggesting that Prep1 regulates the self-renewal ability by controlling the quiescence/proliferation balance. Finally, we show that in FL HSCs Prep1 absence induces the interferon signaling pathway leading to premature cycling and exhaustion of fetal HSCs.Livia ModicaGiorgio IottiAnnalisa D'AvolaFrancesco BlasiPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 9, p e107916 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Livia Modica Giorgio Iotti Annalisa D'Avola Francesco Blasi Prep1 (pKnox1) regulates mouse embryonic HSC cycling and self-renewal affecting the Stat1-Sca1 IFN-dependent pathway.
description	A hypomorphic Prep1 mutation results in embryonic lethality at late gestation with a pleiotropic embryonic phenotype that includes defects in all hematopoietic lineages. Reduced functionality of the hematopoietic stem cells (HSCs) compartment might be responsible for the hematopoietic phenotype observed at mid-gestation. In this paper we demonstrate that Prep1 regulates the number of HSCs in fetal livers (FLs), their clonogenic potential and their ability to de novo generate the hematopoietic system in ablated hosts. Furthermore, we show that Prep1 controls the self-renewal ability of the FL HSC compartment as demonstrated by serial transplantation experiments. The premature exhaustion of Prep1 mutant HSCs correlates with the reduced quiescent stem cell pool thus suggesting that Prep1 regulates the self-renewal ability by controlling the quiescence/proliferation balance. Finally, we show that in FL HSCs Prep1 absence induces the interferon signaling pathway leading to premature cycling and exhaustion of fetal HSCs.
format	article
author	Livia Modica Giorgio Iotti Annalisa D'Avola Francesco Blasi
author_facet	Livia Modica Giorgio Iotti Annalisa D'Avola Francesco Blasi
author_sort	Livia Modica
title	Prep1 (pKnox1) regulates mouse embryonic HSC cycling and self-renewal affecting the Stat1-Sca1 IFN-dependent pathway.
title_short	Prep1 (pKnox1) regulates mouse embryonic HSC cycling and self-renewal affecting the Stat1-Sca1 IFN-dependent pathway.
title_full	Prep1 (pKnox1) regulates mouse embryonic HSC cycling and self-renewal affecting the Stat1-Sca1 IFN-dependent pathway.
title_fullStr	Prep1 (pKnox1) regulates mouse embryonic HSC cycling and self-renewal affecting the Stat1-Sca1 IFN-dependent pathway.
title_full_unstemmed	Prep1 (pKnox1) regulates mouse embryonic HSC cycling and self-renewal affecting the Stat1-Sca1 IFN-dependent pathway.
title_sort	prep1 (pknox1) regulates mouse embryonic hsc cycling and self-renewal affecting the stat1-sca1 ifn-dependent pathway.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/4da127b24861473b9c5b09af932efbfa
work_keys_str_mv	AT liviamodica prep1pknox1regulatesmouseembryonichsccyclingandselfrenewalaffectingthestat1sca1ifndependentpathway AT giorgioiotti prep1pknox1regulatesmouseembryonichsccyclingandselfrenewalaffectingthestat1sca1ifndependentpathway AT annalisadavola prep1pknox1regulatesmouseembryonichsccyclingandselfrenewalaffectingthestat1sca1ifndependentpathway AT francescoblasi prep1pknox1regulatesmouseembryonichsccyclingandselfrenewalaffectingthestat1sca1ifndependentpathway
_version_	1718414279595524096

Prep1 (pKnox1) regulates mouse embryonic HSC cycling and self-renewal affecting the Stat1-Sca1 IFN-dependent pathway.

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