Single-cell RNA Sequencing Reveals Novel Cellular Factors for Response to Immunosuppressive Therapy in Aplastic Anemia

Autor: Jinho Jang, Hongtae Kim, Sung-Soo Park, Miok Kim, Yong Ki Min, Hyoung-oh Jeong, Seunghoon Kim, Taejoo Hwang, David Whee-Young Choi, Hee-Je Kim, Sukgil Song, Dong Oh Kim, Semin Lee, Chang Hoon Lee, Jong Wook Lee
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: HemaSphere, Vol 7, Iss 11, p e977 (2023)
Druh dokumentu: article
ISSN: 2572-9241
00000000
DOI: 10.1097/HS9.0000000000000977
Popis: Aplastic anemia (AA) is a lethal hematological disorder; however, its pathogenesis is not fully understood. Although immunosuppressive therapy (IST) is a major treatment option for AA, one-third of patients do not respond to IST and its resistance mechanism remains elusive. To understand AA pathogenesis and IST resistance, we performed single-cell RNA sequencing (scRNA-seq) of bone marrow (BM) from healthy controls and patients with AA at diagnosis. We found that CD34+ early-stage erythroid precursor cells and PROM1+ hematopoietic stem cells were significantly depleted in AA, which suggests that the depletion of CD34+ early-stage erythroid precursor cells and PROM1+ hematopoietic stem cells might be one of the major mechanisms for AA pathogenesis related with BM-cell hypoplasia. More importantly, we observed the significant enrichment of CD8+ T cells and T cell–activating intercellular interactions in IST responders, indicating the association between the expansion and activation of T cells and the positive response of IST in AA. Taken together, our findings represent a valuable resource offering novel insights into the cellular heterogeneity in the BM of AA and reveal potential biomarkers for IST, building the foundation for future precision therapies in AA.
Databáze: Directory of Open Access Journals
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