Single-cell characterization of immune aplastic anemia reveals convergence of adaptive and innate immunity: in vivo

ABSTRACT: Immune aplastic anemia (AA) is a life-threatening bone marrow (BM) failure disorder driven by an autoimmune T cell attack against the hematopoietic stem and progenitor cells (HSPCs). However, the autoantigen targets and the role of other immune cells are unknown. Here, by combining scRNA+TCRαβ-seq, TCRβ-seq, flow cytometry and plasma cytokine profiling of >250 patients with AA, >250 patients with other hematological disorders and >1,000 healthy controls, we identify NK cells and CD8+ TEMRA cells expressing NK receptors with AA-associated TCRB-seq motifs as the most dysregulated immune cell populations in AA BM. Functional co-culture experiments with scRNA-TCRαβ-seq readout utilizing primary HSPCs and immune cells (in total 55 conditions) provide evidence that NK cells alone cannot kill HSP

INSTRUMENT(S): Illumina NovaSeq 6000

ORGANISM(S): Homo sapiens

SUBMITTER: Jani Huuhtanen 

PROVIDER: E-MTAB-13485 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress