mDia formins form hetero-oligomers and cooperatively maintain murine hematopoiesis

Zhaofeng Li, Meng Su, Xinshu Xie, Pan Wang, Honghao Bi, Ermin Li, Kehan Ren, Lili Dong, Zhiyi Lv, Xuezhen Ma, Yijie Liu, Baobing Zhao, Yuanliang Peng, Jing Liu, Lu Liu, Jing Yang, Peng Ji*, Yang Mei*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

mDia formin proteins regulate the dynamics and organization of the cytoskeleton through their linear actin nucleation and polymerization activities. We previously showed that mDia1 deficiency leads to aberrant innate immune activation and induces myelodysplasia in a mouse model, and mDia2 regulates enucleation and cytokinesis of erythroblasts and the engraftment of hematopoietic stem and progenitor cells (HSPCs). However, whether and how mDia formins interplay and regulate hematopoiesis under physiological and stress conditions remains unknown. Here, we found that both mDia1 and mDia2 are required for HSPC regeneration under stress, such as serial plating, aging, and reconstitution after myeloid ablation. We showed that mDia1 and mDia2 form hetero-oligomers through the interactions between mDia1 GBD-DID and mDia2 DAD domains. Double knockout of mDia1 and mDia2 in hematopoietic cells synergistically impaired the filamentous actin network and serum response factor-involved transcriptional signaling, which led to declined HSPCs, severe anemia, and significant mortality in neonates and newborn mice. Our data demonstrate the potential roles of mDia hetero-oligomerization and their non-rodent functions in the regulation of HSPCs activity and orchestration of hematopoiesis.

Original languageEnglish (US)
Article numbere1011084
JournalPLoS genetics
Volume19
Issue number12
DOIs
StatePublished - Dec 29 2023

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics
  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Cancer Research

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