Haematopoietic Signalling Group, European Cancer Stem Cell Institute, School of Biosciences, Cardiff University, Cardiff, UK.
German Cancer Research Center (DKFZ), Heidelberg, Germany.
Nat Commun. 2022 Apr 19;13(1):2048. doi: 10.1038/s41467-022-29675-w.
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 CD34EPCR(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.
人类 CD34 造血干细胞（HSCs）的异质性阻碍了我们理解 HSCs 在谱系分化过程中所经历的细胞和分子轨迹。通过使用包括单细胞 RNA 测序和广泛的异种移植在内的各种平台，我们发现了一种未被表征的人类 CD34 HSC 群体。这些 CD34EPCR（CD38/CD45RA）（简称为 EPCR）HSCs 具有高再生和自我更新能力，达到了约每 3 个细胞中有 1 个干细胞的频率，这是迄今为止描述的最高频率。它们独特的转录组布线，其中许多与分化细胞谱系相关的基因模块赋予了它们在体内和体外的多谱系谱系输出。在单细胞水平上，EPCR HSCs 是迄今为止定义的转录组和功能上最同质的人类 HSC 群体，也可以在出生后的组织中轻松识别。因此，该 EPCR 群体不仅提供了高分辨率的人类 HSC，还提供了最原始水平上的结构良好的人类造血层次组织。
