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Wilson, N.K.* ; Kent, D.G.* ; Buettner, F. ; Shehata, M.* ; Macaulay, I.C.* ; Calero-Nieto, F.J.* ; Sánchez Castillo, M.* ; Oedekoven, C.A.* ; Diamanti, E.* ; Schulte, R.* ; Ponting, C.P.* ; Voet, T.* ; Caldas, C.* ; Stingl, J.* ; Green, A.R.* ; Theis, F.J. ; Göttgens, B.*

Combined single-cell functional and gene expression analysis resolves heterogeneity within stem cell populations.

Cell Stem Cell 16, 712-724 (2015)
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Heterogeneity within the self-renewal durability of adult hematopoietic stem cells (HSCs) challenges our understanding of the molecular framework underlying HSC function. Gene expression studies have been hampered by the presence of multiple HSC subtypes and contaminating non-HSCs in bulk HSC populations. To gain deeper insight into the gene expression program of murine HSCs, we combined single-cell functional assays with flow cytometric index sorting and single-cell gene expression assays. Through bioinformatic integration of these datasets, we designed an unbiased sorting strategy that separates non-HSCs away from HSCs, and single-cell transplantation experiments using the enriched population were combined with RNA-seq data to identify key molecules that associate with long-term durable self-renewal, producing a single-cell molecular dataset that is linked to functional stem cell activity. Finally, we demonstrated the broader applicability of this approach for linking key molecules with defined cellular functions in another stem cell system.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Hematopoietic Stem; In-vivo; Self-renewal; Rna-seq; Clonal Expansion; Progenitor Cells; Hierarchy; Compartment; Capacity
Language english
Publication Year 2015
HGF-reported in Year 2015
ISSN (print) / ISBN 1934-5909
e-ISSN 1875-9777
Journal Cell Stem Cell
Quellenangaben Volume: 16, Issue: 6, Pages: 712-724 Article Number: , Supplement: ,
Publisher Cell Press
Publishing Place Cambridge, Mass.
Reviewing status Peer reviewed
Institute(s) Institute of Computational Biology (ICB)
POF-Topic(s) 30205 - Bioengineering and Digital Health
Research field(s) Enabling and Novel Technologies
PSP Element(s) G-503800-001
PubMed ID 26004780
DOI 10.1016/j.stem.2015.04.004
WOS ID WOS:000355932300018
Scopus ID 84929646174
Erfassungsdatum 2015-05-27
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