M Klaine

Collège de France, Lutetia Parisorum, Île-de-France, France

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Publications (7)69.25 Total impact

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    ABSTRACT: It is now well established that in all vertebrate species the development of a functional haematopoietic system requires the sequential contribution of two independently generated pools of haematopoietic precursors. These two haematopoietic precursors waves are dedicated to specialized functions regarding haematopoiesis ontogeny. The first, which occurs in the extra-embryonic compartment, in the yolk Sac (YS) blood islands, rapidly produces the differentiated erythro-myeloid cells (erythrocytes, macrophages and megakaryocytes) necessary for developing tissue homeostasis. This extremely fast differentiation seems to occur at the expense of differentiation and maintenance potentials (see below). The second wave of precursors develops in the intra-embryonic compartment, in the aorta region, and gives rise to Haematopoietic Stem Cells (HSC), which are thought to be responsible for lifelong maintenance of haematopoiesis (Cumano and Godin, 2007).
    01/2009: pages 201-215;
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    ABSTRACT: The existence of macrophages (Mphi) of yolk-sac (YS) origin has been reported in all vertebrate models. However, the nature of their precursors and pathways of differentiation have not been elucidated. Phenotypic and differentiation potential analyses of YS at 7.5 to 10 postcoital days (dpc), performed in CX3CR1(GFP) embryos, allowed us to discern 3 independent Mphi populations. A first transient wave consisted of mature, maternal-derived Mphipresent as early as 7.5 to 8 dpc. A second wave of committed Mphi precursors arose at 8 dpc (2-4 somite stage) and was followed by a third wave of erythromyeloid precursors (4-6 somite stage). Both types of precursors displayed similar phenotypes and gave rise to CX3CR1/green fluorescent protein (GFP)-positive Mphi, but differed by their differentiation potential, at the clonal level. The combined data of phenotypic, gene-expression, and in situ analyses allowed us to conclude that the previously named "primitive Mphi" corresponded to a mixture of the first transient wave and committed Mphi precursors. Both YS-derived precursors followed a developmental pathway common to adult Mphi and could be qualified as definitive.
    Blood 12/2005; 106(9):3004-11. · 9.78 Impact Factor
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    ABSTRACT: Little is known about hematopoietic stem cell (HSC) development from mesoderm. To gain more information on the intraembryonic HSC site of origin, we purified multipotent hematopoietic progenitors from the aorta-gonads-mesonephros (AGM) of mice. This population, expressing c-Kit, AA4.1, CD31, and CD41, but not Flk1, and mainly negative for CD45, proved capable of long-term reconstitution in sublethally irradiated Rag2gammac(-/-) recipients. We assigned the expression of GATA-2, GATA-3, and lmo2 to AGM-HSC, whereas erythromyeloid progenitors express only GATA-2. This unique combination of surface markers and transcription factors could be allocated in the AGM to the intraaortic clusters and the subaortic patches underlying aortic endothelial cells. Taken together, those data indicate that embryonic HSCs (i) differ from their fetal liver and adult counterpart by the low expression of CD45, (ii) do not colocalize with aortic endothelial cells as previously thought, and (iii) are localized, at 10.5 days postcoitum, in the splanchnic mesoderm underlying aortic endothelial cells, within GATA-3(+)CD31(+) cell clusters.
    Proceedings of the National Academy of Sciences 02/2005; 102(1):134-9. · 9.81 Impact Factor
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    ABSTRACT: The relative contribution of yolk sac and intraembryonic precursors to hematopoiesis has been a matter of long-standing controversy. As reconstitution activity has so far only been found in embryonic tissues after the onset of circulation, the origin of reconstituting cells could not be formally established. Here, we separated yolk sac and intraembryonic splanchnopleura prior to circulation and maintained the explants in organ culture before transfer. Precursors derived from the intraembryonic site generated multilineage hematopoietic progeny in adult mice for more than 6 months. Yolk sac cells only provided myeloid short-term reconstitution. The results reveal a differential hematopoietic capacity of precirculation embryonic tissues in vivo, and indicate that the only cells capable of adult long-term hematopoiesis are of intraembryonic origin.
    Immunity 10/2001; 15(3):477-85. · 19.80 Impact Factor
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    ABSTRACT: It is now widely accepted that hemopoietic cells born intraembryonically are the best candidates for the seeding of definitive hemopoietic organs. To further understand the mechanisms involved in the generation of definitive hemopoietic stem cells, we analysed the expression of the hemopoietic-related transcription factors Lmo2 and GATA-3 during the early steps of mouse development (7-12 dpc), with a particular emphasis on intraembryonic hemogenic sites. We show here that both Lmo2 and GATA-3 are present in the intraembryonic regions known to give rise to hemopoietic precursors in vitro and in vivo, suggesting that they act together at key points of hemopoietic development. (1) Lmo2 and GATA-3 are expressed in the caudal mesoderm during the phase of intraembryonic precursors determination. (2) A highly transient concomitant expression is observed in the caudal intraembryonic definitive endoderm, suggesting that these factors are involved in the specification of intraembryonic hemopoietic precursors. (3) Lmo2 and GATA-3 are expressed within the hemopoietic clusters located in the aortic floor during fetal liver colonisation. Furthermore, a strong GATA-3 signal allowed us to uncover previously unreported mesodermal aggregates beneath the aorta. A combined in situ and immunocytological analysis strongly suggests that ventral mesodermal GATA-3 patches are involved in the process of intraembryonic stem cell generation.
    Development 03/2000; 127(3):643-53. · 6.21 Impact Factor
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    ABSTRACT: We have identified and characterized the stem cell antigen AA4. This molecule is a type I transmembrane protein whose overall structure suggests a role in cell adhesion. During fetal ontogeny (days 9-14 of development), AA4 is expressed in three major cell types: vascular endothelial cells, aorta-associated hematopoietic clusters, and primitive fetal liver hematopoietic progenitors. In the adult, AA4 is abundant in lung, heart, and whole bone marrow. In the adult hematopoietic compartment, aa4 transcripts are present in bone marrow CD34(-/lo) Lin- Sca-1+ c-Kit+ and CD34hi Lin- Sca-1+ c-Kit+ stem and progenitor cell subsets. Our observations suggest that AA4 plays a role in cell-cell interactions during hematopoietic and vascular development.
    Immunity 07/1999; 10(6):691-700. · 19.80 Impact Factor
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    ABSTRACT: The SCL gene encodes a basic helix-loop-helix transcription factor with a pivotal role in the development of endothelium and of all hematopoietic lineages. SCL is also expressed in the central nervous system, although its expression pattern has not been examined in detail and its function in neural development is unknown. In this article we present the first analysis of SCL transcriptional regulation in vivo. We have identified three spatially distinct regulatory modules, each of which was both necessary and sufficient to direct reporter gene expression in vivo to three different regions within the normal SCL expression domain, namely, developing endothelium, midbrain, and hindbrain/spinal cord. In addition we have demonstrated that GATA factor binding sites are essential for neural expression of the SCL constructs. The midbrain element was particularly powerful and axonal lacZ expression revealed the details of axonal projections, thus implicating SCL in the development of occulomotor, pupillary, or retinotectal pathways. The neural expression pattern of the SCL gene was highly conserved in mouse, chicken, and zebrafish embryos and the 5' region of the chicken SCL locus exhibited a striking degree of functional conservation in transgenic mice. These data suggest that SCL performs critical functions in neural development. The regulatory elements identified here provide important tools for analyzing these functions.
    Developmental Biology 06/1999; 209(1):128-42. · 3.87 Impact Factor