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Resolving fates and single-cell transcriptomes of hematopoietic stem cell clones by PolyloxExpress barcoding

Lineage tracing reveals hematopoietic stem cell (HSC) fates, while single-cell RNA sequencing identifies snapshots of HSC transcriptomes. To obtain information on fate plus transcriptome in the same cell, we developed the PolyloxExpress allele, enabling Cre-recombinase-dependent RNA barcoding in sit...

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Main Authors: Pei, Weike (Author) , Shang, Fuwei (Author) , Wang, Xi (Author) , Fanti, Ann-Kathrin (Author) , Greco, Alessandro (Author) , Busch, Katrin (Author) , Klapproth, Kay (Author) , Zhang, Qin (Author) , Quedenau, Claudia (Author) , Sauer, Sascha (Author) , Feyerabend, Thorsten B. (Author) , Höfer, Thomas (Author) , Rodewald, Hans-Reimer (Author)
Format: Article (Journal)
Language:English
Published: 11 August 2020
In: Cell stem cell
Year: 2020, Volume: 27, Issue: 3, Pages: 383-395.e8
ISSN:1875-9777
DOI:10.1016/j.stem.2020.07.018
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.stem.2020.07.018
Verlag, lizenzpflichtig, Volltext: http://www.sciencedirect.com/science/article/pii/S1934590920303568
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Author Notes:Weike Pei, Fuwei Shang, Xi Wang, Ann-Kathrin Fanti, Alessandro Greco, Katrin Busch, Kay Klapproth, Qin Zhang, Claudia Quedenau, Sascha Sauer, Thorsten B. Feyerabend, Thomas Höfer, Hans-Reimer Rodewald
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Summary:Lineage tracing reveals hematopoietic stem cell (HSC) fates, while single-cell RNA sequencing identifies snapshots of HSC transcriptomes. To obtain information on fate plus transcriptome in the same cell, we developed the PolyloxExpress allele, enabling Cre-recombinase-dependent RNA barcoding in situ. Linking fates to single HSC transcriptomes provided the information required to identify transcriptional signatures of HSC fates, which were not apparent in single-HSC transcriptomes alone. We find that differentiation-inactive, multilineage, and lineage-restricted HSC clones reside in distinct regions of the transcriptional landscape of hematopoiesis. Differentiation-inactive HSC clones are closer to the origin of the transcriptional trajectory, yet they are not characterized by a quiescent gene signature. Fate-specific gene signatures imply coherence of clonal HSC fates, and HSC output toward short-lived lineage progenitors indicates stability of HSC fates over time. These combined analyses of fate and transcriptome under physiological conditions may pave the way toward identifying molecular determinants of HSC fates.
Item Description:Gesehen am 29.10.2020
Physical Description:Online Resource
ISSN:1875-9777
DOI:10.1016/j.stem.2020.07.018

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