Differentiation of transplanted haematopoietic stem cells tracked by single-cell transcriptomic analysis
Open accessAbstract
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.
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Both scRNA-seq and single-cell transplant experiments suggest significant heterogeneity in the lineage commitment of HSCs and other progenitors that otherwise appear to be functionally similar.
“Both scRNA-seq and single-cell transplant experiments suggest significant heterogeneity in the lineage commitment of HSCs and other progenitors that otherwise appear to be functionally similar (Dong et al., 2020).”
From Unraveling Hematopoiesis through the Lens of Genomics (2020) · cites this paper as Dong et al., 2020
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Unraveling Hematopoiesis through the Lens of Genomics
Liggett, L. A., & Sankaran, V. G. (2020) · Cell · doi:10.1016/j.cell.2020.08.030 · Cited by 163 · see citing works
- Authors
- Dong, F., Hao, S., Zhang, S., Zhu, C., Cheng, H., Yang, Z., Hamey, F. K., Wang, X., Gao, A., Wang, F., Gao, Y., Dong, J., Wang, C., Wang, J., Lan, Y., Liu, B., Ema, H., Tang, F., Göttgens, B., Zhu, P., & Cheng, T.
- Affiliations
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- Wellcome/MRC Cambridge Stem Cell Institute (GB)
- Jinan University (CN)
- Peking University (CN)
- Chinese Academy of Sciences (CN)
- Corresponding author
- Göttgens, Berthold
- Zhu, Ping
- Cheng, Tao
- ORCID
- Venue
- Nature Cell Biology
- Published
- 2020-05-04
- Volume
- 22
- Issue
- 6
- Pages
- 630-639
- ISSN
- 1465-7392 (ISSN-L)
- 1476-4679
- OpenAlex
- W3023553925
- Cited by
- 121
- References
- 57
- Citations by year
- 2026: 15 · 2025: 20 · 2024: 26 · 2023: 16 · 2022: 22 · 2021: 17 · 2020: 5
- FWCI
- 9.47
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Locations
- Nature Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- Apollo (University of Cambridge) (submittedVersion)
- Apollo
- Funders
- Wellcome Trust (203151/Z/16/Z)
- Medical Research Council (MR/M008975/1, MC_PC_12009, MC_PC_17230)
- Topics
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Keywords
- hematopoietic stem cells, HSC differentiation, HSC homing, multipotent progenitors, myeloid precursors, myeloablation, HSC expansion, stem cell transplantation
- MeSH terms
- Animals, Cell Cycle, Cell Differentiation, Female, Hematopoietic Stem Cells, Megakaryocytes, Mice, Inbred C57BL, Erythroid Precursor Cells, Cell Lineage, Myeloid Cells, Mice, Single-Cell Analysis, Transcriptome
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