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Resolving fate and transcriptome of hematopoietic stem cell clones

Item Type:Preprint
Title:Resolving fate and transcriptome of hematopoietic stem cell clones
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:Adult bone marrow harbors a mosaic of hematopoietic stem cell (HSC) clones of embryonic origin, and recent work suggests that such clones may have coherent lineage fates. To probe under physiological conditions whether HSC clones with different fates are transcriptionally distinct, we developed PolyloxExpress – a Cre recombinase-dependent DNA substrate for in situ barcoding that allows parallel readout of barcodes and transcriptomes in single cells. We describe differentiation-inactive, multilineage and lineage-restricted HSC clones, find that they reside in distinct regions of the transcriptional landscape of hematopoiesis, and identify corresponding gene signatures. All clone types contain proliferating HSCs, indicating that differentiation-inactive HSCs can undergo symmetric self-renewal. Our work establishes an approach for studying determinants of stem cell fate in vivo and provides molecular evidence for fate coherence of HSC clones.
Keywords:Animals, Mice
Publisher:Cold Spring Harbor Laboratory Press
Article Number:2020.03.25.008433
Date:26 March 2020
Official Publication:https://doi.org/10.1101/2020.03.25.008433

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