Abstract：
:The balance of self-renewal and differentiation in long-term repopulating hematopoietic stem cells (LT-HSC) must be strictly controlled to maintain blood homeostasis and to prevent leukemogenesis. Hematopoietic cytokines can induce differentiation in LT-HSCs; however, the molecular mechanism orchestrating this delicate balance requires further elucidation. We identified the tumor suppressor GADD45G as an instructor of LT-HSC differentiation under the control of differentiation-promoting cytokine receptor signaling. GADD45G immediately induces and accelerates differentiation in LT-HSCs and overrides the self-renewal program by specifically activating MAP3K4-mediated MAPK p38. Conversely, the absence of GADD45G enhances the self-renewal potential of LT-HSCs. Videomicroscopy-based tracking of single LT-HSCs revealed that, once GADD45G is expressed, the development of LT-HSCs into lineage-committed progeny occurred within 36 hr and uncovered a selective lineage choice with a severe reduction in megakaryocytic-erythroid cells. Here, we report an unrecognized role of GADD45G as a central molecular linker of extrinsic cytokine differentiation and lineage choice control in hematopoiesis.
journal_name
Stem Cell Reportsjournal_title
Stem cell reportsauthors
Thalheimer FB,Wingert S,De Giacomo P,Haetscher N,Rehage M,Brill B,Theis FJ,Hennighausen L,Schroeder T,Rieger MAdoi
10.1016/j.stemcr.2014.05.010subject
Has Abstractpub_date
2014-06-19 00:00:00pages
34-43issue
1issn
2213-6711pii
S2213-6711(14)00151-9journal_volume
3pub_type
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