Global S&T Development Trend Analysis Platform of Resources and Environment
DOI | 10.1038/s41467-019-09031-1 |
Lnk/Sh2b3 deficiency restores hematopoietic stem cell function and genome integrity in Fancd2 deficient Fanconi anemia | |
Balcerek, Joanna1,2; Jiang, Jing1,2,3; Li, Yang1,4; Jiang, Qinqin5,6,7; Holdreith, Nicholas1,2; Singh, Brijendra1,2; Chandra, Vemika1,2; Lv, Kaosheng1,2; Ren, Jian-gang1,2; Rozenova, Krasimira1,2; Li, Weihua5,6,7; Greenberg, Roger A.5,6,7; Tong, Wei1,2 | |
2019-03-07 | |
发表期刊 | NATURE COMMUNICATIONS |
ISSN | 2041-1723 |
出版年 | 2018 |
卷号 | 9 |
文章类型 | Article |
语种 | 英语 |
国家 | USA; Peoples R China |
英文摘要 | Fanconi anemia (FA) is a bone marrow failure (BMF) syndrome that arises from mutations in a network of FA genes essential for DNA interstrand crosslink (ICL) repair and replication stress tolerance. While allogeneic stem cell transplantation can replace defective HSCs, interventions to mitigate HSC defects in FA do not exist. Remarkably, we reveal here that Lnk (Sh2b3) deficiency restores HSC function in Fancd2(-/-) mice. Lnk deficiency does not impact ICL repair, but instead stabilizes stalled replication forks in a manner, in part, dependent upon alleviating blocks to cytokine-mediated JAK2 signaling. Lnk deficiency restores proliferation and survival of Fancd2(-/-) HSCs, while reducing replication stress and genomic instability. Furthermore, deletion of LNK in human FA-like HSCs promotes clonogenic growth. These findings highlight a new role for cytokine/JAK signaling in promoting replication fork stability, illuminate replication stress as a major underlying origin of BMF in FA, and have strong therapeutic implications. |
领域 | 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000445561900001 |
WOS关键词 | SELF-RENEWAL ; HOMOLOGOUS RECOMBINATION ; C-MPL ; ENDOGENOUS ALDEHYDES ; BRCA1 DEFICIENCY ; PROGENITOR CELLS ; APLASTIC-ANEMIA ; CROSS-LINKS ; MICE ; REPLICATION |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
URL | 查看原文 |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/204249 |
专题 | 资源环境科学 |
作者单位 | 1.Childrens Hosp Philadelphia, Div Hematol, Philadelphia, PA 19104 USA; 2.Univ Penn, Dept Pediat, Perelman Sch Med, Philadelphia, PA 19104 USA; 3.Yangzhou Univ, Sch Med, Inst Translat Med, Yangzhou 225001, Jiangsu, Peoples R China; 4.Univ Penn, Dept Pathol & Lab Med, Perelman Sch Med, Philadelphia, PA 19104 USA; 5.Univ Penn, Abramson Canc Res Inst, Dept Canc Biol, Philadelphia, PA 19104 USA; 6.Univ Penn, Basser Ctr BRCA, Philadelphia, PA 19104 USA; 7.Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA |
推荐引用方式 GB/T 7714 | Balcerek, Joanna,Jiang, Jing,Li, Yang,et al. Lnk/Sh2b3 deficiency restores hematopoietic stem cell function and genome integrity in Fancd2 deficient Fanconi anemia[J]. NATURE COMMUNICATIONS,2019,9. |
APA | Balcerek, Joanna.,Jiang, Jing.,Li, Yang.,Jiang, Qinqin.,Holdreith, Nicholas.,...&Tong, Wei.(2019).Lnk/Sh2b3 deficiency restores hematopoietic stem cell function and genome integrity in Fancd2 deficient Fanconi anemia.NATURE COMMUNICATIONS,9. |
MLA | Balcerek, Joanna,et al."Lnk/Sh2b3 deficiency restores hematopoietic stem cell function and genome integrity in Fancd2 deficient Fanconi anemia".NATURE COMMUNICATIONS 9(2019). |
条目包含的文件 | 条目无相关文件。 |
除非特别说明,本系统中所有内容都受版权保护,并保留所有权利。
修改评论