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A critical role of FADD in hematopoietic stem and progenitor cells
Author(s) -
Zhang Jianke,
Rosenberg Stephen
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.703.15
Subject(s) - fadd , stem cell , biology , progenitor cell , microbiology and biotechnology , haematopoiesis , cancer research , myeloid , embryonic stem cell , bone marrow , lymphopoiesis , immunology , programmed cell death , apoptosis , caspase , genetics , gene
FADD is required for apoptotic signaling downstream of death receptors, through its association with caspase 8. FADD−/− mice die in utero. A lack of FADD in embryonic stem cells lead to severe defects in T and B cell development as shown by Rag‐1−/− blastocyst complementation assays, implicating FADD as a crucial mediator of lymphopoiesis. However, deletion of FADD following lymphoid lineage commitment did not lead to significant defects in T or B cell development. We reports the generation and analyses of organ‐specific as well as inducible FADD knockout mice in which FADD is deletion in multiple organs/cell types including the liver, hematopoietic stem/progenitor cells and lineage committed myeloid cells in adult animals. FADD deficiency resulted in diminished Fas‐induced apoptosis of hepatocytes, but had no significant impact on liver regeneration. Deletion of FADD specifically in monocytic precursors still allows generation of macrophages. However a lack of FADD leads to impaired maintenance of bone marrow hematopoietic progenitors in vivo. Furthermore, the ability of in vitro and in vivo differentiation into lymphoid, myeloid and erythroid cells were greatly decreased in FADD‐deficient bone marrow progenitor cells. Thus, while dispensable after lineage commitment, FADD plays a critical role in hematopoietic stem/progenitor cells. Studies were supported by NIH/intramural grants.