美国哈佛医学院Alan D. D’Andrea研究组发现,MYC促进范可尼贫血骨髓干细胞功能障碍。该项研究成果于2020年9月29日在线发表在《细胞—干细胞》杂志上。
Title: MYC Promotes Bone Marrow Stem Cell Dysfunction in Fanconi Anemia
Author: Alfredo Rodríguez, Kaiyang Zhang, Anniina Frkkil, Jessica Filiatrault, Chunyu Yang, Martha Velázquez, Elissa Furutani, Devorah C. Goldman, Benilde García de Teresa, Gilda Garza-Mayén, Kelsey McQueen, Larissa A. Sambel, Bertha Molina, Leda Torres, Marisol González, Eduardo Vadillo, Rosana Pelayo, William H. Fleming, Markus Grompe, Akiko Shimamura, Sampsa Hautaniemi, Joel Greenberger, Sara Frías, Kalindi Parmar, Alan D. D’Andrea
Issue&Volume: 2020-09-29
Abstract: Bone marrow failure (BMF) in Fanconi anemia (FA) patients results from dysfunctionalhematopoietic stem and progenitor cells (HSPCs). To identify determinants of BMF,we performed single-cell transcriptome profiling of primary HSPCs from FA patients.In addition to overexpression of p53 and TGF-β pathway genes, we identified high levelsof MYC expression. We correspondingly observed coexistence of distinct HSPC subpopulationsexpressing high levels of TP53 or MYC in FA bone marrow (BM). Inhibiting MYC expression with the BET bromodomain inhibitor(+)-JQ1 reduced the clonogenic potential of FA patient HSPCs but rescued physiologicaland genotoxic stress in HSPCs from FA mice, showing that MYC promotes proliferationwhile increasing DNA damage. MYC-high HSPCs showed significant downregulation of cell adhesion genes, consistent withenhanced egress of FA HSPCs from bone marrow to peripheral blood. We speculate thatMYC overexpression impairs HSPC function in FA patients and contributes to exhaustionin FA bone marrow.
DOI: 10.1016/j.stem.2020.09.004
Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(20)30450-1
Cell Stem Cell:《细胞—干细胞》,创刊于2007年。隶属于细胞出版社,最新IF:21.464
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