Differentiation of transplanted haematopoietic stem cells tracked by single-cell transcriptomic analysis.
Authors
Dong, Fang
Hao, Sha
Zhu, Caiying
Cheng, Hui
Yang, Zining
Wang, Xiaofang
Gao, Ai
Wang, Fengjiao
Dong, Ji
Wang, Chenchen
Liu, Bing
Ema, Hideo
Gottgens, Berthold
Publication Date
2020-06Journal Title
Nature cell biology
ISSN
1465-7392
Publisher
Springer Nature
Volume
22
Issue
6
Pages
630-639
Language
eng
Type
Article
This Version
AM
Physical Medium
Print-Electronic
Metadata
Show full item recordCitation
Dong, F., Hao, S., Zhang, S., Zhu, C., Cheng, H., Yang, Z., Hamey, F. K., et al. (2020). Differentiation of transplanted haematopoietic stem cells tracked by single-cell transcriptomic analysis.. Nature cell biology, 22 (6), 630-639. https://doi.org/10.1038/s41556-020-0512-1
Abstract
How transplanted haematopoietic stem cells (HSCs) reside and behave in a preconditioned host at the early stage has not been studied due to technical limitations. Here, by single-cell RNA-sequencing, we first obtained the transcriptome-based classifications of 28 haematopoietic cell types, and then applied them in conjunction with functional assays to track the dynamic changes of highly purified HSCs in irradiated recipients within the first week after transplantation. Based on our transcriptional classifications, most homed HSCs in bone marrow and spleen were shown to become 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 vigorous 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.
Keywords
Hematopoietic Stem Cells, Megakaryocytes, Myeloid Cells, Animals, Mice, Inbred C57BL, Mice, Cell Cycle, Cell Differentiation, Cell Lineage, Female, Erythroid Precursor Cells, Single-Cell Analysis, Transcriptome
Sponsorship
MRC (MR/K500975/1, MC_PC_12009), Wellcome Trust (203151/Z/16/Z)
Funder references
Wellcome Trust (203151/Z/16/Z)
MRC (MR/K500975/1)
MRC (MC_PC_12009)
Identifiers
External DOI: https://doi.org/10.1038/s41556-020-0512-1
This record's URL: https://www.repository.cam.ac.uk/handle/1810/303053
Rights
All rights reserved