Single cell analyses identify a highly regenerative and homogenous human CD34+ hematopoietic stem cell population

Fernando Anjos-Afonso (), Florian Buettner, Syed A. Mian, Hefin Rhys, Jimena Perez-Lloret, Manuel Garcia-Albornoz, Namrata Rastogi, Linda Ariza-McNaughton and Dominique Bonnet ()
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Fernando Anjos-Afonso: Haematopoietic Signalling Group, European Cancer Stem Cell Institute, School of Biosciences, Cardiff University
Florian Buettner: German Cancer Research Center (DKFZ)
Syed A. Mian: Haematopoietic Stem Cell Lab, The Francis Crick Institute
Hefin Rhys: Flow Cytometry Facility, The Francis Crick Institute
Jimena Perez-Lloret: Advance Sequencing Facility, The Francis Crick Institute
Manuel Garcia-Albornoz: Haematopoietic Stem Cell Lab, The Francis Crick Institute
Namrata Rastogi: Haematopoietic Signalling Group, European Cancer Stem Cell Institute, School of Biosciences, Cardiff University
Linda Ariza-McNaughton: Haematopoietic Stem Cell Lab, The Francis Crick Institute
Dominique Bonnet: Haematopoietic Stem Cell Lab, The Francis Crick Institute

Nature Communications, 2022, vol. 13, issue 1, 1-13

Abstract: Abstract The heterogeneous nature of human CD34+ hematopoietic stem cells (HSCs) has hampered our understanding of the cellular and molecular trajectories that HSCs navigate during lineage commitment. Using various platforms including single cell RNA-sequencing and extensive xenotransplantation, we have uncovered an uncharacterized human CD34+ HSC population. These CD34+EPCR+(CD38/CD45RA)− (simply as EPCR+) HSCs have a high repopulating and self-renewal abilities, reaching a stem cell frequency of ~1 in 3 cells, the highest described to date. Their unique transcriptomic wiring in which many gene modules associated with differentiated cell lineages confers their multilineage lineage output both in vivo and in vitro. At the single cell level, EPCR+ HSCs are the most transcriptomically and functionally homogenous human HSC population defined to date and can also be easily identified in post-natal tissues. Therefore, this EPCR+ population not only offers a high human HSC resolution but also a well-structured human hematopoietic hierarchical organization at the most primitive level.

Date: 2022
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DOI: 10.1038/s41467-022-29675-w

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