Join

Plate IV.535 · Publications

Cytokine-Regulated GADD45G Induces Differentiation and Lineage Selection in Hematopoietic Stem Cells

Article in Stem Cell Reports, July 2014.

Open accessStem Cells, Lineage

  1. Frederic B. Thalheimer
  2. Susanne Wingert
  3. Pangrazio De Giacomo
  4. Nadine Haetscher
  5. Maike Rehage
  6. Boris Brill
  7. Fabian J. Theis
  8. Lothar Hennighausen
  9. Timm Schroeder
  10. Michael A. Rieger

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.

Cite

@article{thalheimer2014cytokine_77db,
  title = {{Cytokine-Regulated GADD45G Induces Differentiation and Lineage Selection in Hematopoietic Stem Cells}},
  author = {Thalheimer, Frederic B. and Wingert, Susanne and De Giacomo, Pangrazio and Haetscher, Nadine and Rehage, Maike and Brill, Boris and Theis, Fabian J. and Hennighausen, Lothar and Schroeder, Timm and Rieger, Michael A.},
  journal = {Stem Cell Reports},
  publisher = {Elsevier BV},
  year = {2014},
  month = jul,
  doi = {10.1016/j.stemcr.2014.05.010},
  url = {https://doi.org/10.1016/j.stemcr.2014.05.010},
  pmid = {25068120},
  pmcid = {PMC4110750}
}
.bib file