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

Pierre Charbord; Claire Pouget; Hans Binder; Florent Dumont; Grégoire Stik; Pacifique Levy; Fabrice Allain; Céline Marchal; Jenna Richter; Benjamin Uzan; Françoise Pflumio; Franck Letourneur; Henry Wirth; Elaine Dzierzak; David Traver; Thierry Jaffredo; Charles Durand

doi:10.1016/j.stem.2014.06.005

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

Pierre Charbord, Claire Pouget, Hans Binder, Florent Dumont, Grégoire Stik, Pacifique Levy, Fabrice Allain, Céline Marchal, Jenna Richter, Benjamin Uzan, Françoise Pflumio, Franck Letourneur, Henry Wirth, Elaine Dzierzak, David Traver, Thierry Jaffredo, Charles Durand

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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 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.

Original language	English (US)
Pages (from-to)	376-391
Number of pages	16
Journal	Cell Stem Cell
Volume	15
Issue number	3
DOIs	https://doi.org/10.1016/j.stem.2014.06.005
State	Published - 2014

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© 2014 Elsevier Inc.

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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. (2014). A systems biology approach for defining the molecular framework of the hematopoietic stem cell Niche. Cell Stem Cell, 15(3), 376-391. https://doi.org/10.1016/j.stem.2014.06.005

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 2014, 'A systems biology approach for defining the molecular framework of the hematopoietic stem cell Niche', Cell Stem Cell, vol. 15, no. 3, pp. 376-391. https://doi.org/10.1016/j.stem.2014.06.005

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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 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.",

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AU - Levy, Pacifique

AU - Allain, Fabrice

AU - Marchal, Céline

AU - Richter, Jenna

AU - Uzan, Benjamin

AU - Pflumio, Françoise

AU - Letourneur, Franck

AU - Wirth, Henry

AU - Dzierzak, Elaine

AU - Traver, David

AU - Jaffredo, Thierry

AU - Durand, Charles

PY - 2014

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

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