祖细胞
造血
生物
再生障碍性贫血
转录组
干细胞
细胞生物学
背景(考古学)
免疫学
骨髓
癌症研究
遗传学
基因表达
基因
古生物学
作者
Caiying Zhu,Liang Yu,Chenchen Wang,Peng Wu,Xuan Li,Yan Gao,Sibin Fan,Lanlan Ai,Liwei Fang,Hongxu Pan,Tao Cheng,Jun Shi,Ping Zhu
出处
期刊:Blood
[American Society of Hematology]
日期:2021-03-24
卷期号:138 (1): 23-33
被引量:24
标识
DOI:10.1182/blood.2020008966
摘要
Aplastic anemia (AA) is a T cell-mediated autoimmune disorder of the hematopoietic system manifested by severe depletion of the hematopoietic stem and progenitor cells (HSPCs). Nonetheless, our understanding of the complex relationship between HSPCs and T cells is still obscure, mainly limited by techniques and the sparsity of HSPCs in the context of bone marrow failure. Here we performed single-cell transcriptome analysis of residual HSPCs and T cells to identify the molecular players from patients with AA. We observed that residual HSPCs in AA exhibited lineage-specific alterations in gene expression and transcriptional regulatory networks, indicating a selective disruption of distinct lineage-committed progenitor pools. In particular, HSPCs displayed frequently altered alternative splicing events and skewed patterns of polyadenylation in transcripts related to DNA damage and repair, suggesting a likely role in AA progression to myelodysplastic syndromes. We further identified cell type-specific ligand-receptor interactions as potential mediators for ongoing HSPCs destruction by T cells. By tracking patients after immunosuppressive therapy (IST), we showed that hematopoiesis remission was incomplete accompanied by IST insensitive interactions between HSPCs and T cells as well as sustained abnormal transcription state. These data collectively constitute the transcriptomic landscape of disrupted hematopoiesis in AA at single-cell resolution, providing new insights into the molecular interactions of engaged T cells with residual HSPCs and render novel therapeutic opportunities for AA.
科研通智能强力驱动
Strongly Powered by AbleSci AI