巨核细胞
川地34
造血干细胞
干细胞因子
癌症研究
体内
血小板生成素
男科
造血干细胞移植
分子生物学
免疫学
作者
Peng Hua,Joanna Hester,George Adigbli,Rong Li,Bethan Psaila,Anindita Roy,Carole J. R. Bataille,Graham Michael Wynne,Thomas R. Jackson,Thomas A. Milne,Angela J. Russell,James O.J. Davies,Irene Roberts,Fadi Issa,Suzanne M. Watt
出处
期刊:Blood
[American Society of Hematology]
日期:2020-11-19
卷期号:136 (21): 2410-2415
被引量:7
标识
DOI:10.1182/blood.2020005357
摘要
Although cytokine-mediated expansion of human hematopoietic stem cells (HSCs) can result in high yields of hematopoietic progenitor cells, this generally occurs at the expense of reduced bone marrow HSC repopulating ability, thereby limiting potential therapeutic applications. Because bromodomain-containing proteins (BCPs) have been demonstrated to regulate mouse HSC self-renewal and stemness, we screened small molecules targeting various BCPs as potential agents for ex vivo expansion of human HSCs. Of 10 compounds tested, only the bromodomain and extra-terminal motif inhibitor CPI203 enhanced the expansion of human cord blood HSCs without losing cell viability in vitro. The expanded cells also demonstrated improved engraftment and repopulation in serial transplantation assays. Transcriptomic and functional studies showed that the expansion of long-term repopulating HSCs was accompanied by synchronized expansion and maturation of megakaryocytes consistent with CPI203-mediated reprogramming of cord blood hematopoietic stem and progenitor cells. This approach may therefore prove beneficial for ex vivo gene editing, for enhanced platelet production, and for the improved usage of cord blood for transplantation research and therapy.
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