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Cell Stem Cell. 2014 Sep 4;15(3):376-391. doi: 10.1016/j.stem.2014.06.005. Epub 2014 Jul 17.

A systems biology approach for defining the molecular framework of the hematopoietic stem cell niche.

Author information

1
INSERM U972, University Paris 11, Hôpital Paul Brousse, 94807 Villejuif, France. Electronic address: pierre.charbord@inserm.fr.
2
Department of Cell and Developmental Biology, University of California, San Diego, La Jolla, CA 92093-0380, USA.
3
Interdisciplinary Center for Bioinformatics, University of Leipzig, 04107 Leipzig, Germany.
4
Genomic Platform, Institut Cochin, INSERM U567, 75014 Paris, France.
5
Sorbonne Universités, UPMC Paris 06, IBPS, UMR 7622, Laboratoire de Biologie du Développement, 75005 Paris; CNRS, INSERM U1156, IBPS, UMR 7622, Laboratoire de Biologie du Développement, 75005 Paris, France.
6
UMR967 INSERM, LSHL/IRCM, CEA, University Paris 7, 92260 Fontenay-aux-Roses, France.
7
Department of Cell Biology, Erasmus Stem Cell Institute, Erasmus Medical Center, P.O. Box 2040, 3000 CA Rotterdam, the Netherlands.
8
Sorbonne Universités, UPMC Paris 06, IBPS, UMR 7622, Laboratoire de Biologie du Développement, 75005 Paris; CNRS, INSERM U1156, IBPS, UMR 7622, Laboratoire de Biologie du Développement, 75005 Paris, France. Electronic address: charles.durand@upmc.fr.

Abstract

Despite progress in identifying the cellular composition of hematopoietic stem/progenitor cell (HSPC) niches, little is known about the molecular requirements of HSPC support. To address this issue, we used a panel of six recognized HSPC-supportive stromal lines and less-supportive counterparts originating from embryonic and adult hematopoietic sites. Through comprehensive transcriptomic meta-analyses, we identified 481 mRNAs and 17 microRNAs organized in a modular network implicated in paracrine signaling. Further inclusion of 18 additional cell strains demonstrated that this mRNA subset was predictive of HSPC support. Our gene set contains most known HSPC regulators as well as a number of unexpected ones, such as Pax9 and Ccdc80, as validated by functional studies in zebrafish embryos. In sum, our approach has identified the core molecular network required for HSPC support. These cues, along with a searchable web resource, will inform ongoing efforts to instruct HSPC ex vivo amplification and formation from pluripotent precursors.

PMID:
25042701
DOI:
10.1016/j.stem.2014.06.005
[Indexed for MEDLINE]
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