N6-methyl-2'-deoxyadenosine promotes self-renewal of BFU-E progenitor in erythropoiesis

Yao Li; Zi-Yu Liang; Hai-Lin Wang

doi:10.1016/j.isci.2023.106924

N6-methyl-2'-deoxyadenosine promotes self-renewal of BFU-E progenitor in erythropoiesis

iScience. 2023 May 19;26(6):106924. doi: 10.1016/j.isci.2023.106924. eCollection 2023 Jun 16.

Authors

Yao Li^{1

2}, Zi-Yu Liang^{1

2}, Hai-Lin Wang^{1

2

3}

Affiliations

¹ State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China.
² University of Chinese Academy of Sciences, Beijing 100049, China.
³ Institute of Environment and Health, Jianghan University, Wuhan, Hubei 430056, China.

Abstract

Red blood cells supply the oxygen required for all human cells and are in demand for emerging blood-loss therapy. Here we identified N6-methyl-2'-deoxyadenosine (6mdA) as an agonist that promotes the hyperproliferation of burst-forming unit erythroid (BFU-E) progenitor cells. In addition, 6mdA represses the apoptosis of erythroid progenitor cells (EPCs). Combined use of with SCF and EPO enabled cultures of isolated BFU-E to be expanded up to 5,000-fold. Transcriptome analysis showed that 6mdA upregulates the expression of the EPC-associated factors c-Kit, Myb, and Gata2 and downregulates that of the erythroid maturation-related transcription factors Gata1, Spi1, and Klf1. Mechanistic studies suggested that 6mdA enhances and prolongs the activation of erythropoiesis-associated master gene c-Kit and its downstream signaling, leading to expansion and accumulation of EPCs. Collectively, we demonstrate that 6mdA can efficiently stimulate the EPC hyperproliferation and provide a new regenerative medicine recipe to improve ex vivo generation of red blood cells.

Keywords: Biochemistry; Cell biology; Molecular biology.