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

Anjos-Afonso, Fernando ORCID: https://orcid.org/0000-0003-4392-488X, Buettner, Florian, Mian, Syed A., Rhys, Hefin, Perez-Lloret, Jimena, Garcia-Albornoz, Manuel, Rastogi, Namrata, Ariza-McNaughton, Linda and Bonnet, Dominique 2022. Single cell analyses identify a highly regenerative and homogenous human CD34+ hematopoietic stem cell population. Nature Communications 13 , 2048. 10.1038/s41467-022-29675-w

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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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Biosciences European Cancer Stem Cell Research Institute (ECSCRI)
Publisher:	Nature Research
ISSN:	2041-1723
Date of First Compliant Deposit:	20 April 2022
Date of Acceptance:	18 March 2022
Last Modified:	29 Jun 2023 08:39
URI:	https://orca.cardiff.ac.uk/id/eprint/149228

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