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Unbiased Single‐Cell Sequencing of Hematopoietic and Immune Cells from Aplastic Anemia Reveals the Contributors of Hematopoiesis Failure and Dysfunctional Immune Regulation.

Authors :
Guo, Rongqun
Kong, Jingjing
Tang, Ping
Wang, Shuya
Sang, Lina
Liu, Liu
Guo, Rong
Yan, Ketai
Qi, Mochu
Bian, Zhilei
Song, Yongping
Jiang, Zhongxing
Li, Yingmei
Source :
Advanced Science; 3/13/2024, Vol. 11 Issue 10, p1-17, 17p
Publication Year :
2024

Abstract

Aplastic anemia (AA) is a bone marrow (BM) failure syndrome mediated by hyperactivated T‐cells with heterogeneous pathogenic factors. The onset of BM failure cannot be accurately determined in humans; therefore, exact pathogenesis remains unclear. In this study, a cellular atlas and microenvironment interactions is established using unbiased single‐cell RNA‐seq, along with multi‐omics analyses (mass cytometry, cytokine profiling, and oxidized fatty acid metabolomics). A new KIR+CD8+ regulatory T cells (Treg) subset is identified in patients with AA that engages in immune homeostasis. Conventional CD4+ T‐cells differentiate into highly differentiated T helper cells with type 2 cytokines (IL‐4, IL‐6, and IL‐13), GM‐SCF, and IL‐1β. Immunosuppressive homeostasis is impaired by enhanced apoptosis of activated Treg cells. Pathological Vδ1 cells dominated the main fraction of γδ T‐cells. The B/plasma, erythroid, and myeloid lineages also exhibit substantial pathological features. Interactions between TNFSF12‐TNFRSF12A, TNF‐TNFRSF1A, and granzyme‐gasdermin are associated with the cell death of hematopoietic stem/progenitor (HSPCs), Treg, and early erythroid cells. Ferroptosis, a major driver of HSPCs destruction, is identified in patients with AA. Furthermore, a case of twins with AA is reported to enhance the persuasiveness of the analysis. These results collectively constitute the cellular atlas and microenvironment interactions in patients with AA and provide novel insights into the development of new therapeutic opportunities. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
21983844
Volume :
11
Issue :
10
Database :
Complementary Index
Journal :
Advanced Science
Publication Type :
Academic Journal
Accession number :
176012178
Full Text :
https://doi.org/10.1002/advs.202304539