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 |
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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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