Cytokine-regulated GADD45G induces differentiation and lineage selection in hematopoietic stem cells
Thalheimer FB, Wingert S, De Giacomo P, Haetscher N, Rehage M, Brill B, Theis FJ, Hennighausen L, Schroeder T, Rieger MA (2014)
Publication Type: Journal article
Publication year: 2014
Journal
Book Volume: 3
Pages Range: 34-43
Journal Issue: 1
DOI: 10.1016/j.stemcr.2014.05.010
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. © 2014 The Authors.
Involved external institutions
Goethe-Universität Frankfurt am Main
Germany (DE)
Institut für Tumorbiologie und experimentelle Therapie / Chemotherapeutisches Forschungsinstitut Georg-Speyer-Haus
Germany (DE)
Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt (HMGU) / Helmholtz Munich
Germany (DE)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK / NIDDKD)
United States (USA) (US)
Eidgenössische Technische Hochschule Zürich (ETHZ) / Swiss Federal Institute of Technology in Zurich
Switzerland (CH)
Germany (DE)
Institut für Tumorbiologie und experimentelle Therapie / Chemotherapeutisches Forschungsinstitut Georg-Speyer-Haus
Germany (DE)
Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt (HMGU) / Helmholtz Munich
Germany (DE)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK / NIDDKD)
United States (USA) (US)
Eidgenössische Technische Hochschule Zürich (ETHZ) / Swiss Federal Institute of Technology in Zurich
Switzerland (CH)
How to cite
APA:
Thalheimer, F.B., Wingert, S., De Giacomo, P., Haetscher, N., Rehage, M., Brill, B.,... Rieger, M.A. (2014). Cytokine-regulated GADD45G induces differentiation and lineage selection in hematopoietic stem cells. Stem Cell Reports, 3(1), 34-43. https://dx.doi.org/10.1016/j.stemcr.2014.05.010
MLA:
Thalheimer, Frederic B., et al. "Cytokine-regulated GADD45G induces differentiation and lineage selection in hematopoietic stem cells." Stem Cell Reports 3.1 (2014): 34-43.
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