Cytokine-regulated GADD45G induces differentiation and lineage selection in hematopoietic stem cells
- 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.
Author: | Frederic Bastian ThalheimerORCiDGND, Susanne WingertGND, Pangrazio de Giacomo, Nadine Hätscher, Maike Rehage, Boris Brill, Fabian J. Theis, Lothar HennighausenORCiD, Timm Schroeder, Michael A. RiegerORCiDGND |
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URN: | urn:nbn:de:hebis:30:3-343738 |
DOI: | https://doi.org/10.1016/j.stemcr.2014.05.010 |
ISSN: | 2213-6711 |
Parent Title (English): | Stemm cell report |
Publisher: | Cell Press |
Place of publication: | Maryland Heights, MO |
Document Type: | Article |
Language: | English |
Date of Publication (online): | 2014/07/08 |
Date of first Publication: | 2014/07/08 |
Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
Release Date: | 2015/07/27 |
Volume: | 3 |
Issue: | 1 |
Page Number: | 10 |
First Page: | 34 |
Last Page: | 43 |
Note: | This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/). |
HeBIS-PPN: | 369713788 |
Institutes: | Medizin / Medizin |
Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
Sammlungen: | Universitätspublikationen |
Licence (German): | Creative Commons - Namensnennung-Nicht kommerziell-Keine Bearbeitung 3.0 |