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

Accepted version
Peer-reviewed

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Authors

Dong, Fang 
Hao, Sha 
Zhu, Caiying 
Cheng, Hui 

Abstract

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.

Description

Keywords

Animals, Cell Cycle, Cell Differentiation, Cell Lineage, Erythroid Precursor Cells, Female, Hematopoietic Stem Cells, Megakaryocytes, Mice, Mice, Inbred C57BL, Myeloid Cells, Single-Cell Analysis, Transcriptome

Journal Title

Nat Cell Biol

Conference Name

Journal ISSN

1465-7392
1476-4679

Volume Title

22

Publisher

Springer Science and Business Media LLC

Rights

All rights reserved
Sponsorship
Wellcome Trust (203151/Z/16/Z)
MRC (MR/K500975/1)
Medical Research Council (MC_PC_12009)
Medical Research Council (MR/M008975/1)
Medical Research Council (MC_PC_17230)
MRC (MR/K500975/1, MC_PC_12009), Wellcome Trust (203151/Z/16/Z)