Blockade of the interaction between BMP9 and endoglin on erythroid progenitors promotes erythropoiesis in mice

Ayami Yamaguchi, Ikuo Hirano, Shiho Narusawa, Kiyoshi Shimizu, Hiroyuki Ariyama, Kengo Yamawaki, Kenji Nagao, Masayuki Yamamoto, Ritsuko Shimizu

Research output: Contribution to journalArticlepeer-review

Abstract

Bone morphogenetic protein-9 (BMP9), a member of the transforming growth factor β (TGFβ) superfamily, plays important roles in the development and maintenance of various cell lineages via complexes of type I and type II TGFβ receptors. Endoglin is a coreceptor for several TGFβ family members, including BMP9, which is highly expressed in a particular stage of differentiation in erythroid cells as well as in endothelial cells. Although the importance of the interaction between BMP9 and endoglin for endothelial development has been reported, the contribution of BMP9 to endoglin-expressing erythroid cells remains to be clarified. To address this point, we prepared an anti-BMP9 antibody that blocks the BMP9-endoglin interaction. Of note, challenge with the antibody promotes erythropoiesis in wild-type mice but not in a mouse model of renal anemia in which erythropoietin (EPO) production in the kidneys is genetically ablated. While endoglin-positive erythroid progenitors are mainly maintained as progenitors when bone marrow-derived lineage-negative and cKit-positive cells are cultured in the presence of EPO and stem cell factor, the erythroid-biased accumulation of progenitors is impeded by the presence of BMP9. Our findings uncover an unrecognized role for BMP9 in attenuating erythroid differentiation via its interaction with endoglin on erythroid progenitors.

Original languageEnglish
Pages (from-to)782-797
Number of pages16
JournalGenes to Cells
Volume26
Issue number10
DOIs
Publication statusPublished - 2021 Oct

Keywords

  • antibody
  • BMP9
  • endoglin
  • erythropoiesis

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

Fingerprint

Dive into the research topics of 'Blockade of the interaction between BMP9 and endoglin on erythroid progenitors promotes erythropoiesis in mice'. Together they form a unique fingerprint.

Cite this