4.8 Article

Bone marrow sinusoidal endothelium controls terminal erythroid differentiation and reticulocyte maturation

Journal

NATURE COMMUNICATIONS
Volume 12, Issue 1, Pages -

Publisher

NATURE PORTFOLIO
DOI: 10.1038/s41467-021-27161-3

Keywords

-

Funding

  1. Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) [259332240 - RTG 2099, 5454871 - SFB TR 23, 394046768 - SFB 1366, 314905040 - SFB-TR 209]
  2. Ministry of Science, Research and the Arts Baden-Wurttemberg (MWK)
  3. German Research Foundation (DFG) [INST 35/1314-1 FUGG, INST 35/1503-1 FUGG]

Ask authors/readers for more resources

The study reveals that endothelial cells in the bone marrow microenvironment play a critical role in hematopoiesis, with overactivation leading to anemia. Activation of the Wnt signaling pathway affects the differentiation of red blood cells.
Niche crosstalk with Haematopoietic cells underlies normal haematopoiesis and myeloid disorders. Here the authors report a Stabilin2-Cre driver mouse with Cre-activity restricted to bone marrow sinusoidal endothelial cells, and that Stabilin2-Cre driven overactivation of b-catenin leads to erythroid differentiation defects and anaemia. Within the bone marrow microenvironment, endothelial cells (EC) exert important functions. Arterial EC support hematopoiesis while H-type capillaries induce bone formation. Here, we show that BM sinusoidal EC (BM-SEC) actively control erythropoiesis. Mice with stabilized beta-catenin in BM-SEC (Ctnnb1(OE-SEC)) generated by using a BM-SEC-restricted Cre mouse line (Stab2-iCreF3) develop fatal anemia. While activation of Wnt-signaling in BM-SEC causes an increase in erythroblast subsets (PII-PIV), mature erythroid cells (PV) are reduced indicating impairment of terminal erythroid differentiation/reticulocyte maturation. Transplantation of Ctnnb1(OE-SEC) hematopoietic stem cells into wildtype recipients confirms lethal anemia to be caused by cell-extrinsic, endothelial-mediated effects. Ctnnb1(OE-SEC) BM-SEC reveal aberrant sinusoidal differentiation with altered EC gene expression and perisinusoidal ECM deposition and angiocrine dysregulation with de novo endothelial expression of FGF23 and DKK2, elevated in anemia and involved in vascular stabilization, respectively. Our study demonstrates that BM-SEC play an important role in the bone marrow microenvironment in health and disease.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.8
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available