ZFIN ID: ZDB-PUB-140722-21
A Systems Biology Approach for Defining the Molecular Framework of the Hematopoietic Stem Cell Niche
Charbord, P., Pouget, C., Binder, H., Dumont, F., Stik, G., Levy, P., Allain, F., Marchal, C., Richter, J., Uzan, B., Pflumio, F., Letourneur, F., Wirth, H., Dzierzak, E., Traver, D., Jaffredo, T., Durand, C.
Date: 2014
Source: Cell Stem Cell   15(3): 376-91 (Journal)
Registered Authors: Traver, David
Keywords: none
MeSH Terms:
  • Animals
  • Cell Line
  • Embryo, Nonmammalian/metabolism
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Gene Regulatory Networks
  • Hematopoietic Stem Cells/cytology*
  • Hematopoietic Stem Cells/metabolism*
  • Humans
  • Mice, Inbred C57BL
  • MicroRNAs/genetics
  • MicroRNAs/metabolism
  • RNA, Messenger/genetics
  • RNA, Messenger/metabolism
  • Reproducibility of Results
  • Signal Transduction
  • Stem Cell Niche/genetics*
  • Stromal Cells/metabolism
  • Systems Biology/methods*
  • Transcriptome/genetics
  • Zebrafish/embryology
PubMed: 25042701 Full text @ Cell Stem Cell
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.