title: A systems biology approach for defining the molecular framework of the hematopoietic stem cell niche.
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.
authors.affiliation: INSERM U972, University Paris 11, Hôpital Paul Brousse, 94807 Villejuif, France. Electronic address: pierre.charbord@inserm.fr.
authors.forename: Pierre
authors.initials: P
authors.lastname: Charbord
authors.affiliation: Department of Cell and Developmental Biology, University of California, San Diego, La Jolla, CA 92093-0380, USA.
authors.forename: Claire
authors.initials: C
authors.lastname: Pouget
authors.affiliation: Interdisciplinary Center for Bioinformatics, University of Leipzig, 04107 Leipzig, Germany.
authors.forename: Hans
authors.initials: H
authors.lastname: Binder
authors.affiliation: Genomic Platform, Institut Cochin, INSERM U567, 75014 Paris, France.
authors.forename: Florent
authors.initials: F
authors.lastname: Dumont
authors.affiliation: 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.
authors.forename: Grégoire
authors.initials: G
authors.lastname: Stik
authors.affiliation: 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.
authors.forename: Pacifique
authors.initials: P
authors.lastname: Levy
authors.affiliation: 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.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Allain
authors.affiliation: 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.
authors.forename: Céline
authors.initials: C
authors.lastname: Marchal
authors.affiliation: Department of Cell and Developmental Biology, University of California, San Diego, La Jolla, CA 92093-0380, USA.
authors.forename: Jenna
authors.initials: J
authors.lastname: Richter
authors.affiliation: UMR967 INSERM, LSHL/IRCM, CEA, University Paris 7, 92260 Fontenay-aux-Roses, France.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Uzan
authors.affiliation: UMR967 INSERM, LSHL/IRCM, CEA, University Paris 7, 92260 Fontenay-aux-Roses, France.
authors.forename: Françoise
authors.initials: F
authors.lastname: Pflumio
authors.affiliation: Genomic Platform, Institut Cochin, INSERM U567, 75014 Paris, France.
authors.forename: Franck
authors.initials: F
authors.lastname: Letourneur
authors.affiliation: Interdisciplinary Center for Bioinformatics, University of Leipzig, 04107 Leipzig, Germany.
authors.forename: Henry
authors.initials: H
authors.lastname: Wirth
authors.affiliation: Department of Cell Biology, Erasmus Stem Cell Institute, Erasmus Medical Center, P.O. Box 2040, 3000 CA Rotterdam, the Netherlands.
authors.forename: Elaine
authors.initials: E
authors.lastname: Dzierzak
authors.affiliation: Department of Cell and Developmental Biology, University of California, San Diego, La Jolla, CA 92093-0380, USA.
authors.forename: David
authors.initials: D
authors.lastname: Traver
authors.affiliation: 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.
authors.forename: Thierry
authors.initials: T
authors.lastname: Jaffredo
authors.affiliation: 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.
authors.forename: Charles
authors.initials: C
authors.lastname: Durand
mesh_terms: D000818:Animals; D002460:Cell Line; D004625:Embryo, Nonmammalian / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism*; D006801:Humans; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015203:Reproducibility of Results; D015398:Signal Transduction; D055153:Stem Cell Niche / Q000235:genetics*; D017154:Stromal Cells / Q000378:metabolism; D049490:Systems Biology / Q000379:methods*; D059467:Transcriptome / Q000235:genetics; D015027:Zebrafish / Q000196:embryology
chemical_list: D035683:MicroRNAs; D012333:RNA, Messenger