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 metaanalyses, we identified 481 mRNAs and 17 micro-RNAs 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.
Bibliographical noteFunding Information:
We are very grateful to Catherine Robin (Hubrecht Institute) for critical and constructive comments on this study. We thank David Stachura (Department of Cell and Developmental Biology, UCSD) for critical reading of the manuscript. We thank Nicole Boggetto (Institut Jacques Monod, ImagoSeine Bioimaging Core Facility) for cell sorting experiments. We also thank Sophie Gournet (UMR CNRS 7622) for her excellent photographic and drawing assistance. These studies were supported by grants from the Fondation pour la Recherche Médicale (DEQ20100318258) and Agence Nationale pour la Recherche/California Institute for Regenerative Medicine (ANR/CIRM 0001-02).