Gdf15 regulates murine stress erythroid progenitor proliferation and the development of the stress erythropoiesis niche.
Blood Adv
; 3(14): 2205-2217, 2019 07 23.
Article
in En
| MEDLINE
| ID: mdl-31324641
ABSTRACT
Anemic stress induces the proliferation of stress erythroid progenitors in the murine spleen that subsequently differentiate to generate erythrocytes to maintain homeostasis. This process relies on the interaction between stress erythroid progenitors and the signals generated in the splenic erythroid niche. In this study, we demonstrate that although growth-differentiation factor 15 (Gdf15) is not required for steady-state erythropoiesis, it plays an essential role in stress erythropoiesis. Gdf15 acts at 2 levels. In the splenic niche, Gdf15-/- mice exhibit defects in the monocyte-derived expansion of the splenic niche, resulting in impaired proliferation of stress erythroid progenitors and production of stress burst forming unit-erythroid cells. Furthermore, Gdf15 signaling maintains the hypoxia-dependent expression of the niche signal, Bmp4, whereas in stress erythroid progenitors, Gdf15 signaling regulates the expression of metabolic enzymes, which contribute to the rapid proliferation of stress erythroid progenitors. Thus, Gdf15 functions as a comprehensive regulator that coordinates the stress erythroid microenvironment with the metabolic status of progenitors to promote stress erythropoiesis.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Stress, Physiological
/
Erythroid Precursor Cells
/
Erythropoiesis
/
Stem Cell Niche
/
Growth Differentiation Factor 15
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Blood Adv
Year:
2019
Document type:
Article