TY  - JOUR
A1  - Thalheimer, Frederic Bastian
A1  - Wingert, Susanne
A1  - Giacomo, Pangrazio de
A1  - Hätscher, Nadine
A1  - Rehage, Maike
A1  - Brill, Boris
A1  - Theis, Fabian J.
A1  - Hennighausen, Lothar
A1  - Schroeder, Timm
A1  - Rieger, Michael A.
T1  - Cytokine-regulated GADD45G induces differentiation and lineage selection in hematopoietic stem cells
T2  - Stemm cell report
N2  - 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.
Y1  - 2014
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/34373
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-343738
SN  - 2213-6711
N1  - This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).
VL  - 3
IS  - 1
SP  - 34
EP  - 43
PB  - Cell Press
CY  - Maryland Heights, MO
ER  -