N6-methyl-2′-deoxyadenosine promotes self-renewal of BFU-E progenitor in erythropoiesis
In: iScience, Jg. 26 (2023), Heft 6, S. 106924-
Online
academicJournal
Zugriff:
Summary: 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.
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N6-methyl-2′-deoxyadenosine promotes self-renewal of BFU-E progenitor in erythropoiesis
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Autor/in / Beteiligte Person: | Li, Yao ; Liang, Zi-Yu ; Wang, Hai-Lin |
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Zeitschrift: | iScience, Jg. 26 (2023), Heft 6, S. 106924- |
Veröffentlichung: | Elsevier, 2023 |
Medientyp: | academicJournal |
ISSN: | 2589-0042 (print) |
DOI: | 10.1016/j.isci.2023.106924 |
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