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

Anjos-Afonso, Fernando; Buettner, Florian; Mian, Syed A; Rhys, Hefin; Perez-Lloret, Jimena; Garcia-Albornoz, Manuel; Rastogi, Namrata; ... Bonnet, Dominique; + view all (2022) Single cell analyses identify a highly regenerative and homogenous human CD34+ hematopoietic stem cell population. Nature Communications , 13 (1) , Article 2048. 10.1038/s41467-022-29675-w. Green open access

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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.

Type: Article
Title: Single cell analyses identify a highly regenerative and homogenous human CD34+ hematopoietic stem cell population
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/s41467-022-29675-w
Publisher version: https://doi.org/10.1038/s41467-022-29675-w
Language: English
Additional information: Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Keywords: Adult stem cells, Haematopoiesis, Haematopoietic stem cells, Self-renewal
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > The Ear Institute
URI: https://discovery.ucl.ac.uk/id/eprint/10172497
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