Bone marrow sinusoidal endothelium controls terminal erythroid differentiation and reticulocyte maturation.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 34845225.
- Also identified by DOI 10.1038/s41467-021-27161-3 and PMC identifier 8630019.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
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 β-catenin in BM-SEC (Ctnnb1<sup>OE-SEC</sup>) 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<sup>OE-SEC</sup> hematopoietic stem cells into wildtype recipients confirms lethal anemia to be caused by cell-extrinsic, endothelial-mediated effects. Ctnnb1<sup>OE-SEC</sup> 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.
Medical subject headings
- Anemia
- Bone Marrow
- Cell Adhesion Molecules, Neuronal
- Endothelium, Vascular
- Erythroblasts
- Erythropoiesis
- beta Catenin