Mapping healthy HPSC variations to diagnose haematopoietic abnormalities

Researchers generated a first-of-its-kind single-cell RNA sequencing atlas of healthy circulating haematopoietic stem and progenitor cells (HSPCs). This atlas serves amongst others as a reference map for the creation of blood-based diagnostics and analytics for various haematopoietic abnormalities.

“The haematopoietic system is constantly formed by the differentiation of stem cells into specialised cells,” started Dr Nili Furer (Weizmann Institute of Science, Israel). “While we have established reference values for matured cells, we do not have relevant reference values for progenitor states. We need to capture these values to know which values are part of healthy variation and what values may be related to diseases.” For this purpose, Dr Furer and co-investigators analysed HSPCs from peripheral blood samples from 99 individuals [1].

In total, 360,000 single cells were retrieved and categorised as common lymphoid progenitors or multipotent myeloid progenitors. Dr Furer commented that the inter-individual variation in circulating HPSCs is large in healthy individuals (see Figure), whereas intra-individual cell type frequencies were stable across time. The generated data was then applied as a healthy reference map. Using HSPCs derived from blood samples of 100 cytopenic study participants and an additional 100 healthy participants, they validated their atlas and compared healthy and diseased states. Indeed, the additional set of 100 samples from healthy individuals fitted in the healthy variation of the reference map, whereas progressive dissimilarities were seen in cytopenic patients, validating their unique dataset.

Figure: Inter-individual variation in circulating HSPC compositions in healthy individuals [1]



BEMP, basophil eosinophil mast progenitor; ERYP, primitive erythroid cells; MEP(-L-E), megakaryocyte-erythroid progenitors (-L-E); GMP, granulocyte-macrophage progenitors; MPP, multipotent progenitors; HSC, hematopoietic stem cells; CLP(-E-M-L), common lymphoid progenitors (-E-M-L); NKTDP, natural killer- T-and dendritic cell progenitors.

1. Furer N, et al. Natural and age-related variation in circulating human hematopoietic stem cells. Plenary abstracts session, EHA 2023 Annual Congress, 8─11 June, Frankfurt, Germany.

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Posted on 2 August, 202328 March, 2024