CD63 acts as a functional marker in maintaining hematopoietic stem cell quiescence through supporting TGFβ signaling in mice

• Published in: Cell death and differentiation Vol. 29; no. 1; pp. 178 - 191
• Main Authors: Hu, Mengjia, Lu, Yukai, Wang, Song, Zhang, Zihao, Qi, Yan, Chen, Naicheng, Shen, Mingqiang, Chen, Fang, Chen, Mo, Yang, Lijing, Chen, Shilei, Zeng, Dongfeng, Wang, Fengchao, Su, Yongping, Xu, Yang, Wang, Junping
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 01.01.2022; Nature Publishing Group UK
• Subjects: 5-Fluorouracil; Animals; Bone Marrow; CD63 antigen; Cell self-renewal; Cell surface; Hematopoiesis; Hematopoietic stem cells; Hematopoietic Stem Cells - metabolism; Mice; Mice, Knockout; Population studies; Radiation; Stem cells; Transforming Growth Factor beta - metabolism
• ISSN: 1350-9047; 1476-5403
• DOI: 10.1038/s41418-021-00848-2

Hematopoietic stem cell (HSC) fate is tightly controlled by various regulators, whereas the underlying mechanism has not been fully uncovered due to the high heterogeneity of these populations. In this study, we identify tetraspanin CD63 as a novel functional marker of HSCs in mice. We show that CD63 is unevenly expressed on the cell surface in HSC populations. Importantly, HSCs with high CD63 expression (CD63 ) are more quiescent and have more robust self-renewal and myeloid differentiation abilities than those with negative/low CD63 expression (CD63 ). On the other hand, using CD63 knockout mice, we find that loss of CD63 leads to reduced HSC numbers in the bone marrow. In addition, CD63-deficient HSCs exhibit impaired quiescence and long-term repopulating capacity, accompanied by increased sensitivity to irradiation and 5-fluorouracil treatment. Further investigations demonstrate that CD63 is required to sustain TGFβ signaling activity through its interaction with TGFβ receptors I and II, thereby playing an important role in regulating the quiescence of HSCs. Collectively, our data not only reveal a previously unrecognized role of CD63 but also provide us with new insights into HSC heterogeneity.