The HOXB4 homeoprotein promotes the ex vivo enrichment of functional human embryonic stem cell-derived NK cells.

Human embryonic stem cells (hESCs) can be induced to differentiate into blood cells using either co-culture with stromal cells or following human embryoid bodies (hEBs) formation. It is now well established that the HOXB4 homeoprotein promotes the expansion of human adult hematopoietic stem cells (H...

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Autores principales:	Aniya Larbi, Jean-Marc Gombert, Céline Auvray, Bruno l'Homme, Aurélie Magniez, Olivier Féraud, Laure Coulombel, Alain Chapel, Maria Teresa Mitjavila-Garcia, Ali G Turhan, Rima Haddad, Annelise Bennaceur-Griscelli
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/1afe0bb554324a78bf62305ab2e4b8ec
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spelling	oai:doaj.org-article:1afe0bb554324a78bf62305ab2e4b8ec2021-11-18T07:14:15ZThe HOXB4 homeoprotein promotes the ex vivo enrichment of functional human embryonic stem cell-derived NK cells.1932-620310.1371/journal.pone.0039514https://doaj.org/article/1afe0bb554324a78bf62305ab2e4b8ec2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22761810/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Human embryonic stem cells (hESCs) can be induced to differentiate into blood cells using either co-culture with stromal cells or following human embryoid bodies (hEBs) formation. It is now well established that the HOXB4 homeoprotein promotes the expansion of human adult hematopoietic stem cells (HSCs) but also myeloid and lymphoid progenitors. However, the role of HOXB4 in the development of hematopoietic cells from hESCs and particularly in the generation of hESC-derived NK-progenitor cells remains elusive. Based on the ability of HOXB4 to passively enter hematopoietic cells in a system that comprises a co-culture with the MS-5/SP-HOXB4 stromal cells, we provide evidence that HOXB4 delivery promotes the enrichment of hEB-derived precursors that could differentiate into fully mature and functional NK. These hEB-derived NK cells enriched by HOXB4 were characterized according to their CMH class I receptor expression, their cytotoxic arsenal, their expression of IFNγ and CD107a after stimulation and their lytic activity. Furthermore our study provides new insights into the gene expression profile of hEB-derived cells exposed to HOXB4 and shows the emergence of CD34(+)CD45RA(+) precursors from hEBs indicating the lymphoid specification of hESC-derived hematopoietic precursors. Altogether, our results outline the effects of HOXB4 in combination with stromal cells in the development of NK cells from hESCs and suggest the potential use of HOXB4 protein for NK-cell enrichment from pluripotent stem cells.Aniya LarbiJean-Marc GombertCéline AuvrayBruno l'HommeAurélie MagniezOlivier FéraudLaure CoulombelAlain ChapelMaria Teresa Mitjavila-GarciaAli G TurhanRima HaddadAnnelise Bennaceur-GriscelliPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 6, p e39514 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Aniya Larbi Jean-Marc Gombert Céline Auvray Bruno l'Homme Aurélie Magniez Olivier Féraud Laure Coulombel Alain Chapel Maria Teresa Mitjavila-Garcia Ali G Turhan Rima Haddad Annelise Bennaceur-Griscelli The HOXB4 homeoprotein promotes the ex vivo enrichment of functional human embryonic stem cell-derived NK cells.
description	Human embryonic stem cells (hESCs) can be induced to differentiate into blood cells using either co-culture with stromal cells or following human embryoid bodies (hEBs) formation. It is now well established that the HOXB4 homeoprotein promotes the expansion of human adult hematopoietic stem cells (HSCs) but also myeloid and lymphoid progenitors. However, the role of HOXB4 in the development of hematopoietic cells from hESCs and particularly in the generation of hESC-derived NK-progenitor cells remains elusive. Based on the ability of HOXB4 to passively enter hematopoietic cells in a system that comprises a co-culture with the MS-5/SP-HOXB4 stromal cells, we provide evidence that HOXB4 delivery promotes the enrichment of hEB-derived precursors that could differentiate into fully mature and functional NK. These hEB-derived NK cells enriched by HOXB4 were characterized according to their CMH class I receptor expression, their cytotoxic arsenal, their expression of IFNγ and CD107a after stimulation and their lytic activity. Furthermore our study provides new insights into the gene expression profile of hEB-derived cells exposed to HOXB4 and shows the emergence of CD34(+)CD45RA(+) precursors from hEBs indicating the lymphoid specification of hESC-derived hematopoietic precursors. Altogether, our results outline the effects of HOXB4 in combination with stromal cells in the development of NK cells from hESCs and suggest the potential use of HOXB4 protein for NK-cell enrichment from pluripotent stem cells.
format	article
author	Aniya Larbi Jean-Marc Gombert Céline Auvray Bruno l'Homme Aurélie Magniez Olivier Féraud Laure Coulombel Alain Chapel Maria Teresa Mitjavila-Garcia Ali G Turhan Rima Haddad Annelise Bennaceur-Griscelli
author_facet	Aniya Larbi Jean-Marc Gombert Céline Auvray Bruno l'Homme Aurélie Magniez Olivier Féraud Laure Coulombel Alain Chapel Maria Teresa Mitjavila-Garcia Ali G Turhan Rima Haddad Annelise Bennaceur-Griscelli
author_sort	Aniya Larbi
title	The HOXB4 homeoprotein promotes the ex vivo enrichment of functional human embryonic stem cell-derived NK cells.
title_short	The HOXB4 homeoprotein promotes the ex vivo enrichment of functional human embryonic stem cell-derived NK cells.
title_full	The HOXB4 homeoprotein promotes the ex vivo enrichment of functional human embryonic stem cell-derived NK cells.
title_fullStr	The HOXB4 homeoprotein promotes the ex vivo enrichment of functional human embryonic stem cell-derived NK cells.
title_full_unstemmed	The HOXB4 homeoprotein promotes the ex vivo enrichment of functional human embryonic stem cell-derived NK cells.
title_sort	hoxb4 homeoprotein promotes the ex vivo enrichment of functional human embryonic stem cell-derived nk cells.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/1afe0bb554324a78bf62305ab2e4b8ec
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The HOXB4 homeoprotein promotes the ex vivo enrichment of functional human embryonic stem cell-derived NK cells.

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