Identification and characterization of in vitro expanded hematopoietic stem cells.
HSC expansion
hematopoiesis
hematopoietic stem cells
self-renewal gene signature
single cell biology
Journal
EMBO reports
ISSN: 1469-3178
Titre abrégé: EMBO Rep
Pays: England
ID NLM: 100963049
Informations de publication
Date de publication:
06 10 2022
06 10 2022
Historique:
revised:
21
07
2022
received:
27
05
2022
accepted:
27
07
2022
pubmed:
17
8
2022
medline:
12
10
2022
entrez:
16
8
2022
Statut:
ppublish
Résumé
Hematopoietic stem cells (HSCs) cultured outside the body are the fundamental component of a wide range of cellular and gene therapies. Recent efforts have achieved > 200-fold expansion of functional HSCs, but their molecular characterization has not been possible since the majority of cells are non-HSCs and single cell-initiated cultures have substantial clone-to-clone variability. Using the Fgd5 reporter mouse in combination with the EPCR surface marker, we report exclusive identification of HSCs from non-HSCs in expansion cultures. By directly linking single-clone functional transplantation data with single-clone gene expression profiling, we show that the molecular profile of expanded HSCs is similar to proliferating fetal HSCs and reveals a gene expression signature, including Esam, Prdm16, Fstl1, and Palld, that can identify functional HSCs from multiple cellular states. This "repopulation signature" (RepopSig) also enriches for HSCs in human datasets. Together, these findings demonstrate the power of integrating functional and molecular datasets to better derive meaningful gene signatures and opens the opportunity for a wide range of functional screening and molecular experiments previously not possible due to limited HSC numbers.
Identifiants
pubmed: 35971894
doi: 10.15252/embr.202255502
pmc: PMC9535767
doi:
Substances chimiques
Endothelial Protein C Receptor
0
Follistatin-Related Proteins
0
Transcription Factors
0
FSTL1 protein, human
158709-61-6
Banques de données
GEO
['GSE175400']
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e55502Subventions
Organisme : Medical Research Council
ID : MC_PC_17230
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/V005502/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : 203151/Z/16/Z
Pays : United Kingdom
Organisme : Blood Cancer UK
ID : 15008
Pays : United Kingdom
Informations de copyright
© 2022 The Authors. Published under the terms of the CC BY 4.0 license.
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