Jean-charles Boisset - Academia.edu (original) (raw)

Papers by Jean-charles Boisset

Research paper thumbnail of Unravelling the molecular events leading to hematopoietic stem cell generation in the mouse embryo aorta

Research paper thumbnail of Progressive maturation toward hematopoietic stem cells in the mouse embryo aorta

Blood, 2014

Clusters of cells attached to the endothelium of the main embryonic arteries were first observed ... more Clusters of cells attached to the endothelium of the main embryonic arteries were first observed a century ago. Present in most vertebrate species, such clusters, or intraaortic hematopoietic clusters (IAHCs), derive from specialized hemogenic endothelial cells and contain the first few hematopoietic stem cells (HSCs) generated during embryonic development. However, some discrepancies remained concerning the spatio-temporal appearance and the numbers of IAHCs and HSCs. Therefore, the exact cell composition and function of IAHCs remain unclear to date. We show here that IAHCs contain pre-HSCs (or HSC precursors) that can mature into HSCs in vivo (as shown by the successful long-term multilineage reconstitution of primary neonates and secondary adult recipients). Such IAHC pre-HSCs could contribute to the HSC pool increase observed at midgestation. The novel insights in pre-HSC to HSC transition represent an important step toward generating transplantable HSCs in vitro that are needed for autologous HSC transplantation therapies.

Research paper thumbnail of Origine endothéliale des cellules souches hématopoïétiques

médecine/sciences, 2011

> Les cellules souches hématopoïétiques (CSH) sont à l'origine de toutes les cellules sanguines p... more > Les cellules souches hématopoïétiques (CSH) sont à l'origine de toutes les cellules sanguines produites au cours de la vie d'un organisme. Elles apparaissent pendant la vie embryonnaire, période pendant laquelle elles vont transiter par différents organes hématopoïétiques avant de finalement coloniser la moelle osseuse. L'origine exacte des CSH reste encore, à ce jour, un sujet de controverse. En effet, plusieurs candidats au titre « d'ancêtre des CSH » ont été proposés. Nous faisons ici la synthèse de ces différentes théories et de leur validité à la lumière des données les plus récentes, notamment celles qu'offrent les techniques d'imagerie confocale in vivo. < médullaires 1 et le sang de cordon ombilical sont des sources de CSH utilisées pour les transplantations dans les déficits constitutionnels ou acquis du tissu hématopoïétique, les hémopathies (par exemple : leucémies) ou comme adjuvant dans le traitement des tumeurs solides. Les CSH sont toutefois en quantité très restreinte, ce qui limite considérablement leur étude et leur utilisation. Malgré une connaissance de plus en plus précise de la régulation des CSH, notamment chez l'adulte, il est toujours très difficile de reproduire in vitro les conditions appropriées à leur survie et leur expansion sans induire leur différenciation ou leur transformation maligne. Il est également impossible de générer efficacement des CSH in vitro, y compris à partir de cellules souches embryonnaires (CSE) ou de cellules souches pluripotentes reprogrammées (iPS, induced pluripotent stem). Une connaissance plus approfondie de l'origine des CSH adultes, ainsi que des mécanismes régulateurs contrôlant leurs production, survie et expansion, reste donc toujours d'actualité et d'une grande importance tant d'un point de vue fondamental que clinique.

Research paper thumbnail of On the origin of hematopoietic stem cells: Progress and controversy

Stem Cell Research, 2012

This article appeared in a journal published by Elsevier. The attached copy is furnished to the a... more This article appeared in a journal published by Elsevier. The attached copy is furnished to the author for internal non-commercial research and education use, including for instruction at the authors institution and sharing with colleagues.

Research paper thumbnail of The microtubule plus-end tracking protein CLASP2 is required for hematopoiesis and hematopoietic stem cell maintenance

Cell reports, Jan 25, 2012

Mammalian CLASPs are microtubule plus-end tracking proteins whose essential function as regulator... more Mammalian CLASPs are microtubule plus-end tracking proteins whose essential function as regulators of microtubule behavior has been studied mainly in cultured cells. We show here that absence of murine CLASP2 in vivo results in thrombocytopenia, progressive anemia, and pancytopenia, due to defects in megakaryopoiesis, in erythropoiesis, and in the maintenance of hematopoietic stem cell activity. Furthermore, microtubule stability and organization are affected upon attachment of Clasp2 knockout hematopoietic stem-cell-enriched populations, and these cells do not home efficiently toward their bone marrow niche. Strikingly, CLASP2-deficient hematopoietic stem cells contain severely reduced mRNA levels of c-Mpl, which encodes the thrombopoietin receptor, an essential factor for megakaryopoiesis and hematopoietic stem cell maintenance. Our data suggest that thrombopoietin signaling is impaired in Clasp2 knockout mice. We propose that the CLASP2-mediated stabilization of microtubules is r...

Research paper thumbnail of Ex vivo time-lapse confocal imaging of the mouse embryo aorta

Research paper thumbnail of In vivo imaging of haematopoietic cells emerging from the mouse aortic endothelium

Research paper thumbnail of Imaging the founder of adult hematopoiesis in the mouse embryo aorta

Research paper thumbnail of CD41 is developmentally regulated and differentially expressed on mouse hematopoietic stem cells

Research paper thumbnail of Integrin αIIb (CD41) plays a role in the maintenance of hematopoietic stem cell activity in the mouse embryonic aorta

Biology open, Jan 15, 2013

Integrins are transmembrane receptors that play important roles as modulators of cell behaviour t... more Integrins are transmembrane receptors that play important roles as modulators of cell behaviour through their adhesion properties and the initiation of signaling cascades. The αIIb integrin subunit (CD41) is one of the first cell surface markers indicative of hematopoietic commitment. αIIb pairs exclusively with β3 to form the αIIbβ3 integrin. β3 (CD61) also pairs with αv (CD51) to form the αvβ3 integrin. The expression and putative role of these integrins during mouse hematopoietic development is as yet unknown. We show here that hematopoietic stem cells (HSCs) differentially express αIIbβ3 and αvβ3 integrins throughout development. Whereas the first HSCs generated in the aorta at mid-gestation express both integrins, HSCs from the placenta only express αvβ3, and most fetal liver HSCs do not express either integrin. By using αIIb deficient embryos, we show that αIIb is not only a reliable HSC marker but it also plays an important and specific function in maintaining the HSC activit...

Research paper thumbnail of Unravelling the molecular events leading to hematopoietic stem cell generation in the mouse embryo aorta

Research paper thumbnail of Progressive maturation toward hematopoietic stem cells in the mouse embryo aorta

Blood, 2014

Clusters of cells attached to the endothelium of the main embryonic arteries were first observed ... more Clusters of cells attached to the endothelium of the main embryonic arteries were first observed a century ago. Present in most vertebrate species, such clusters, or intraaortic hematopoietic clusters (IAHCs), derive from specialized hemogenic endothelial cells and contain the first few hematopoietic stem cells (HSCs) generated during embryonic development. However, some discrepancies remained concerning the spatio-temporal appearance and the numbers of IAHCs and HSCs. Therefore, the exact cell composition and function of IAHCs remain unclear to date. We show here that IAHCs contain pre-HSCs (or HSC precursors) that can mature into HSCs in vivo (as shown by the successful long-term multilineage reconstitution of primary neonates and secondary adult recipients). Such IAHC pre-HSCs could contribute to the HSC pool increase observed at midgestation. The novel insights in pre-HSC to HSC transition represent an important step toward generating transplantable HSCs in vitro that are needed for autologous HSC transplantation therapies.

Research paper thumbnail of Origine endothéliale des cellules souches hématopoïétiques

médecine/sciences, 2011

> Les cellules souches hématopoïétiques (CSH) sont à l'origine de toutes les cellules sanguines p... more > Les cellules souches hématopoïétiques (CSH) sont à l'origine de toutes les cellules sanguines produites au cours de la vie d'un organisme. Elles apparaissent pendant la vie embryonnaire, période pendant laquelle elles vont transiter par différents organes hématopoïétiques avant de finalement coloniser la moelle osseuse. L'origine exacte des CSH reste encore, à ce jour, un sujet de controverse. En effet, plusieurs candidats au titre « d'ancêtre des CSH » ont été proposés. Nous faisons ici la synthèse de ces différentes théories et de leur validité à la lumière des données les plus récentes, notamment celles qu'offrent les techniques d'imagerie confocale in vivo. < médullaires 1 et le sang de cordon ombilical sont des sources de CSH utilisées pour les transplantations dans les déficits constitutionnels ou acquis du tissu hématopoïétique, les hémopathies (par exemple : leucémies) ou comme adjuvant dans le traitement des tumeurs solides. Les CSH sont toutefois en quantité très restreinte, ce qui limite considérablement leur étude et leur utilisation. Malgré une connaissance de plus en plus précise de la régulation des CSH, notamment chez l'adulte, il est toujours très difficile de reproduire in vitro les conditions appropriées à leur survie et leur expansion sans induire leur différenciation ou leur transformation maligne. Il est également impossible de générer efficacement des CSH in vitro, y compris à partir de cellules souches embryonnaires (CSE) ou de cellules souches pluripotentes reprogrammées (iPS, induced pluripotent stem). Une connaissance plus approfondie de l'origine des CSH adultes, ainsi que des mécanismes régulateurs contrôlant leurs production, survie et expansion, reste donc toujours d'actualité et d'une grande importance tant d'un point de vue fondamental que clinique.

Research paper thumbnail of On the origin of hematopoietic stem cells: Progress and controversy

Stem Cell Research, 2012

This article appeared in a journal published by Elsevier. The attached copy is furnished to the a... more This article appeared in a journal published by Elsevier. The attached copy is furnished to the author for internal non-commercial research and education use, including for instruction at the authors institution and sharing with colleagues.

Research paper thumbnail of The microtubule plus-end tracking protein CLASP2 is required for hematopoiesis and hematopoietic stem cell maintenance

Cell reports, Jan 25, 2012

Mammalian CLASPs are microtubule plus-end tracking proteins whose essential function as regulator... more Mammalian CLASPs are microtubule plus-end tracking proteins whose essential function as regulators of microtubule behavior has been studied mainly in cultured cells. We show here that absence of murine CLASP2 in vivo results in thrombocytopenia, progressive anemia, and pancytopenia, due to defects in megakaryopoiesis, in erythropoiesis, and in the maintenance of hematopoietic stem cell activity. Furthermore, microtubule stability and organization are affected upon attachment of Clasp2 knockout hematopoietic stem-cell-enriched populations, and these cells do not home efficiently toward their bone marrow niche. Strikingly, CLASP2-deficient hematopoietic stem cells contain severely reduced mRNA levels of c-Mpl, which encodes the thrombopoietin receptor, an essential factor for megakaryopoiesis and hematopoietic stem cell maintenance. Our data suggest that thrombopoietin signaling is impaired in Clasp2 knockout mice. We propose that the CLASP2-mediated stabilization of microtubules is r...

Research paper thumbnail of Ex vivo time-lapse confocal imaging of the mouse embryo aorta

Research paper thumbnail of In vivo imaging of haematopoietic cells emerging from the mouse aortic endothelium

Research paper thumbnail of Imaging the founder of adult hematopoiesis in the mouse embryo aorta

Research paper thumbnail of CD41 is developmentally regulated and differentially expressed on mouse hematopoietic stem cells

Research paper thumbnail of Integrin αIIb (CD41) plays a role in the maintenance of hematopoietic stem cell activity in the mouse embryonic aorta

Biology open, Jan 15, 2013

Integrins are transmembrane receptors that play important roles as modulators of cell behaviour t... more Integrins are transmembrane receptors that play important roles as modulators of cell behaviour through their adhesion properties and the initiation of signaling cascades. The αIIb integrin subunit (CD41) is one of the first cell surface markers indicative of hematopoietic commitment. αIIb pairs exclusively with β3 to form the αIIbβ3 integrin. β3 (CD61) also pairs with αv (CD51) to form the αvβ3 integrin. The expression and putative role of these integrins during mouse hematopoietic development is as yet unknown. We show here that hematopoietic stem cells (HSCs) differentially express αIIbβ3 and αvβ3 integrins throughout development. Whereas the first HSCs generated in the aorta at mid-gestation express both integrins, HSCs from the placenta only express αvβ3, and most fetal liver HSCs do not express either integrin. By using αIIb deficient embryos, we show that αIIb is not only a reliable HSC marker but it also plays an important and specific function in maintaining the HSC activit...