Differentiation of transplanted haematopoietic stem cells tracked by single-cell transcriptomic analysis

• Published in: Nature cell biology Vol. 22; no. 6; pp. 630 - 639
• Main Authors: Dong, Fang, Hao, Sha, Zhang, Sen, Zhu, Caiying, Cheng, Hui, Yang, Zining, Hamey, Fiona K, Wang, Xiaofang, Gao, Ai, Wang, Fengjiao, Gao, Yun, Dong, Ji, Wang, Chenchen, Wang, Jinyong, Lan, Yu, Liu, Bing, Ema, Hideo, Tang, Fuchou, Göttgens, Berthold, Zhu, Ping, Cheng, Tao
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 01.06.2020
• Subjects: Analysis; Animals; Bone marrow; Bone marrow transplantation; Cell Cycle; Cell Differentiation; Cell Lineage; Differentiation; Erythroid Precursor Cells - cytology; Erythroid Precursor Cells - metabolism; Female; Gene expression; Gene sequencing; Hematopoietic stem cells; Hematopoietic Stem Cells - cytology; Hematopoietic Stem Cells - metabolism; Kinetics; Megakaryocytes - cytology; Megakaryocytes - metabolism; Mice; Mice, Inbred C57BL; Myeloid Cells - cytology; Myeloid Cells - metabolism; Ribonucleic acid; RNA; RNA sequencing; Single-Cell Analysis - methods; Spleen; Stem cell transplantation; Stem cells; Therapeutic applications; Transcription; Transcriptome; Transplantation; China
• ISSN: 1465-7392; 1476-4679
• DOI: 10.1038/s41556-020-0512-1

How transplanted haematopoietic stem cells (HSCs) behave soon after they reside in a preconditioned host has not been studied due to technical limitations. Here, using single-cell RNA sequencing, we first obtained the transcriptome-based classifications of 28 haematopoietic cell types. We then applied them in conjunction with functional assays to track the dynamic changes of immunophenotypically purified HSCs in irradiated recipients within the first week after transplantation. Based on our transcriptional classifications, most homed HSCs in bone marrow and spleen became multipotent progenitors and, occasionally, some HSCs gave rise to megakaryocytic-erythroid or myeloid precursors. Parallel in vitro and in vivo functional experiments supported the paradigm of robust differentiation without substantial HSC expansion during the first week. Therefore, this study uncovers the previously inaccessible kinetics and fate choices of transplanted HSCs in myeloablated recipients at early stage, with implications for clinical applications of HSCs and other stem cells.