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

Fiche publication


Date publication

septembre 2017

Journal

Blood advances

Auteurs

Membres identifiés du Cancéropôle Est :
Dr GACHET Christian


Tous les auteurs :
Brouard N, Jost C, Matthias N, Albrecht C, Egard S, Gandhi P, Strassel C, Inoue T, Sugiyama D, Simmons PJ, Gachet C, Lanza F

Résumé

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 CD45TER119CD31CD51VCAM-1PDGFRα (VP) phenotype that lacked colony-forming unit fibroblast activity and harbored an hepatocyte progenitor signature. This previously undescribed VP 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 VP 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.

Référence

Blood Adv. 2017 Sep 26;1(21):1854-1866