A unique microenvironment in the developing liver supports the expansion of megakaryocyte progenitors

Nathalie Brouard, Camille Jost, Nadine Matthias, Camille Albrecht, Sébastien Egard, Poojabahen Gandhi, Catherine Strassel, Tomoko Inoue, Daisuke Sugiyama, Paul J. Simmons, Christian Gachet, Francois Lanza

    Research output: Contribution to journalArticlepeer-review

    10 Citations (Scopus)

    Abstract

    The fetal liver is the site of a major expansion of the hematopoietic stem cell (HSC) pool and is also a privileged organ to study megakaryocyte progenitor differentiation. We identified in the mouse fetal liver at day 13.5 a discrete stromal cell population harboring a CD45-TER119-CD31-CD51+VCAM-1+PDGFRα- (V+P-) phenotype that lacked colonyforming unit fibroblast activity and harbored an hepatocyte progenitor signature. This previously undescribed V1P2 population efficiently supported megakaryocyte production from mouse bone marrow HSC and human peripheral blood HSC-myeloid progenitors cultured in the presence of limited cytokine concentrations. Megakaryocytes obtained in V1P2 cocultures were polyploid, positive for CD41/CD42c, and efficiently produced proplatelets. Megakaryocyte production appeared to be mediated by an expansion of the progenitor compartment through HSC-stromal cell contact. In conclusion, the fetal liver contains a unique cellular microenvironment that could represent a platform for the discovery of regulators of megakaryopoiesis.

    Original languageEnglish
    Pages (from-to)1854-1866
    Number of pages13
    JournalBlood Advances
    Volume1
    Issue number21
    DOIs
    Publication statusPublished - Sep 26 2017

    All Science Journal Classification (ASJC) codes

    • Hematology

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