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

Item Type:Article
Title:Resolving fates and single-cell transcriptomes of hematopoietic stem cell clones by PolyloxExpress barcoding
Creators Name:Pei, W. and Shang, F. and Wang, X. and Fanti, A.K. and Greco, A. and Busch, K. and Klapproth, K. and Zhang, Q. and Quedenau, C. and Sauer, S. and Feyerabend, T.B. and Höfer, T. and Rodewald, H.R.
Abstract: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.
Keywords:Hematopoietic Stem Cells, Hematopoietic Stem Cell Fates, High-Resolution RNA Barcoding, Lineage Tracing, Single-Cell Transcriptomics, Transcriptional Landscape, Clonal Fate Coherence, Hematopoietic Stem Cell Quiescence
Source:Cell Stem Cell
Publisher:Cell Press
Page Range:383-395
Date:3 September 2020
Official Publication:https://doi.org/10.1016/j.stem.2020.07.018
PubMed:View item in PubMed

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