Mitochondria transfer mediates stress erythropoiesis by altering the bioenergetic profiles of early erythroblast via cd47

In our study, we demonstrated the functional importance of intercellular mitochondria transfer to mediate bioenergetic profiles of recipient erythroblasts to facilitate their recovery from anemic stress. We also identified a subset of metabolically active erythroid populations with higher abundance of mitochondria transfer marked by CD47. 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 alpha 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 alpha interaction in the early stages of erythroblasts.