title: The HOXB4 homeoprotein promotes the ex vivo enrichment of functional human embryonic stem cell-derived NK cells.
abstract: 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.
authors: Inserm UMR 935, ESTeam Paris Sud, Stem Cell Core Facility Institut André Lwoff, University Paris Sud 11, Paul Brousse Hospital, Villejuif, France.
authors: Aniya
authors: A
authors: Larbi
authors: Jean-Marc
authors: JM
authors: Gombert
authors: Céline
authors: C
authors: Auvray
authors: Bruno
authors: B
authors: l'Homme
authors: Aurélie
authors: A
authors: Magniez
authors: Olivier
authors: O
authors: Féraud
authors: Laure
authors: L
authors: Coulombel
authors: Alain
authors: A
authors: Chapel
authors: Maria Teresa
authors: MT
authors: Mitjavila-Garcia
authors: Ali G
authors: AG
authors: Turhan
authors: Rima
authors: R
authors: Haddad
authors: Annelise
authors: A
authors: Bennaceur-Griscelli
mesh_terms: D002454:Cell Differentiation / Q000502:physiology*; D002460:Cell Line; D018920:Coculture Techniques; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007694:Killer Cells, Natural / Q000166:cytology / Q000378:metabolism*; D017154:Stromal Cells / Q000166:cytology / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: C090460:HOXB4 protein, human; D018398:Homeodomain Proteins; D014157:Transcription Factors