Mitochondria Transfer Mediates Stress Erythropoiesis by Altering the Bioenergetic Profiles of early Erythroblasts through CD47 (J Exp Med, Sep 2022)

Chong Yang 1Rui Yokomori 1Lee Hui Chua 1Shi Hao Tan 1Darren Qiancheng Tan 1Kenichi Miharada 2Takaomi Sanda 1Toshio Suda 1 2

Affiliations

  • 1Cancer Science Institute of Singapore, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
  • 2International Research Centre for Medical Sciences, Kumamoto University, Kumamoto, Japan.

Abstract

Intercellular mitochondria transfer is a biological phenomenon implicated in diverse biological processes. However, the physiological role of this phenomenon remains understudied between erythroblasts and their erythroblastic island (EBI) macrophage niche. To gain further insights into the mitochondria transfer functions, we infused EBI macrophages in vivo into mice subjected to different modes of anemic stresses. Interestingly, we observed the occurrence of mitochondria transfer events from the infused EBI macrophages to early stages of erythroblasts coupled with enhanced erythroid recovery. Single-cell RNA-sequencing analysis on erythroblasts receiving exogenous mitochondria revealed a subset of highly proliferative and metabolically active erythroid populations marked by high expression of CD47. Furthermore, CD47 or Sirp? blockade leads to a decline in both the occurrence of mitochondria transfer events and their mediated erythroid recovery. Hence, these data indicate a significant role of mitochondria transfer in the enhancement of erythroid recovery from stress through the alteration of the bioenergetic profiles via CD47-Sirp? interaction in the early stages of erythroblasts.

PMID: 36112140  DOI: 10.1084/jem.20220685