HSPCs display within-family homogeneity in differentiation and proliferation despite population heterogeneity
Abstract
High-throughput single cell methods have uncovered substantial heterogeneity in the pool of hematopoietic stem and progenitor cells (HSPCs), but how much instruction is inherited by offspring from their heterogeneous ancestors remains unanswered. Using a method that enables simultaneous determination of common ancestor, division number, and differentiation status of a large collection of single cells, our data revealed that murine cells that derived from a common ancestor had significant similarities in their division progression and differentiation outcomes. Although each family diversifies, the overall collection of cell types observed is composed of homogeneous families. Heterogeneity between families could be explained, in part, by differences in ancestral expression of cell-surface markers. Our analyses demonstrate that fate decision by cells are largely inherited from ancestor cells, indicating the importance of common ancestor effects. These results may have ramifications for bone marrow transplantation and leukemia, where substantial heterogeneity in HSPC behavior is observed.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files. Source data has been provided for Figures 1-4 in supplemental File 1.
Article and author information
Author details
Funding
Bettencourt-Schue (ATIP-Avenir)
- Leïla Perié
Labex CelTisPhyBio (ANR-10-LBX-0038)
- Leïla Perié
Idex (Paris-Sciece-Lettres Program ANR-10-IDEX-0001-02 PSL)
- Leïla Perié
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All the experimental procedures were approved by the local ethics committee (Comité d'Ethique en expérimentation animale de l'Institut Curie) under approval number DAP 2016 006.
Copyright
© 2021, Tak et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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