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

doi:10.1182/bloodadvances.2016003541

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 journal › Article › peer-review

15 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 language	English
Pages (from-to)	1854-1866
Number of pages	13
Journal	Blood Advances
Volume	1
Issue number	21
DOIs	https://doi.org/10.1182/bloodadvances.2016003541
Publication status	Published - Sept 26 2017

All Science Journal Classification (ASJC) codes

Hematology

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10.1182/bloodadvances.2016003541

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title = "A unique microenvironment in the developing liver supports the expansion of megakaryocyte progenitors",

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.",

author = "Nathalie Brouard and Camille Jost and Nadine Matthias and Camille Albrecht and S{\'e}bastien Egard and Poojabahen Gandhi and Catherine Strassel and Tomoko Inoue and Daisuke Sugiyama and Simmons, {Paul J.} and Christian Gachet and Francois Lanza",

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doi = "10.1182/bloodadvances.2016003541",

language = "English",

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T1 - A unique microenvironment in the developing liver supports the expansion of megakaryocyte progenitors

AU - Brouard, Nathalie

AU - Jost, Camille

AU - Matthias, Nadine

AU - Albrecht, Camille

AU - Egard, Sébastien

AU - Gandhi, Poojabahen

AU - Strassel, Catherine

AU - Inoue, Tomoko

AU - Sugiyama, Daisuke

AU - Simmons, Paul J.

AU - Gachet, Christian

AU - Lanza, Francois

PY - 2017/9/26

Y1 - 2017/9/26

N2 - 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.

AB - 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.

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

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