Differentiation of transplanted haematopoietic stem cells tracked by single-cell transcriptomic analysis.
Journal
Nature cell biology
ISSN: 1476-4679
Titre abrégé: Nat Cell Biol
Pays: England
ID NLM: 100890575
Informations de publication
Date de publication:
06 2020
06 2020
Historique:
received:
21
06
2019
accepted:
30
03
2020
pubmed:
6
5
2020
medline:
17
9
2020
entrez:
6
5
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 32367048
doi: 10.1038/s41556-020-0512-1
pii: 10.1038/s41556-020-0512-1
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
630-639Subventions
Organisme : Medical Research Council
ID : MC_PC_17230
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 203151/Z/16/Z
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/K500975/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_PC_12009
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/M008975/1
Pays : United Kingdom
Commentaires et corrections
Type : CommentIn
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