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Bone morphogenetic protein 4 modulates c‐Kit expression and differentiation potential in murine embryonic aorta‐gonad‐mesonephros haematopoiesis in vitro
Author(s) -
Marshall Caroline J.,
Sinclair Joanna C.,
Thrasher Adrian J.,
Kin Christine
Publication year - 2007
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.2007.06795.x
Subject(s) - haematopoiesis , embryonic stem cell , biology , microbiology and biotechnology , stem cell , progenitor cell , cd34 , stem cell factor , bone morphogenetic protein 4 , bone morphogenetic protein , immunology , genetics , gene
Summary The transforming growth factor‐ β ‐related factor bone morphogenetic protein 4 (BMP4) is expressed in the human embryonic aorta‐gonad‐mesonephros (AGM) coincident with the emergence of haematopoietic cells and influences postnatal mammalian haematopoietic stem cells in vitro . To investigate the role of BMP4 in mammalian embryonic haematopoiesis, cells were isolated from murine AGM and two populations of CD34 + cells with different levels of c‐Kit expression and multipotency were identified. CD34 + /c‐Kit high cells express CD45 and are haematopoietic‐restricted progenitors. In contrast, CD34 + /c‐Kit low cells are Flk1+/CD45 neg and generate adherent colonies in ex vivo culture that resemble haemangioblast colonies identified in other systems. The addition of BMP4 to AGM cells resulted in expansion of the CD34 + /c‐Kit low cell pool within 48 h, via a combination of down modulation of the c‐Kit receptor in CD34 + /c‐Kit high cells and proliferation. In long‐term culture, BMP4 increased the growth/survival of CD34 + /c‐Kit high haematopoietic progenitors, effects that were blocked by BMP inhibitors. CD34 + /c‐Kit high progenitors cultured with BMP4 also generated adherent colonies typical of c‐Kit low cells. These results suggest that BMP4 regulates c‐Kit expression and differentiation potential in CD34 + AGM cells and supports a role for BMP signalling in the maintenance of multipotency during embryonic haematopoiesis, providing an insight into stem cell homeostasis within the mammalian haematopoietic niche.