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A reference model for circulating hematopoietic stem cells with applications to diagnostics

ABSTRACT: A reference model for circulating hematopoietic stem cells with applications to diagnostics

PROVIDER: PRJEB85241 | ENA |

REPOSITORIES: ENA

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A reference model for circulating hematopoietic stem cells with applications to diagnostics

Project description:With aging, deviation of human blood counts from their normal range accompanies the transition from health to hematological and other diseases. Hematopoietic stem and progenitor cells (HSPCs) deliver life-long multi-lineage output, but their variation across healthy humans and their diagnostic utility haven’t been characterized. To address this, we introduce an HSPC reference model using single-cell profiling of circulating CD34+ cells (cHSPCs) from 148 healthy individuals. We characterize physiological cHSPC composition, link it with standard blood counts and show that the ratio between lymphoid and myeloid progenitors is decreased in ageing males. Using this new reference model, we develop sensitive tools which could be used for diagnostics of myelodysplastic syndrome (MDS) from peripheral blood without bone marrow analysis. Profiling cHSPC compositions leads to the discovery of new MDS subclasses, ranging in their lymphocyte, basophil and granulocyte progenitor frequencies. The data and methodologies presented herein highlight the role of reference modeling in promoting clinical applications of single-cell genomics in MDS and in the future for other diseases too. This dataset can be explored as metacells at https://apps.tanaylab.com/MCV/blood_aging (for more about metacells, see https://github.com/tanaylab/metacells and https://doi.org/10.1186/s13059-022-02667-1).

2025-01-06 | GSE285943 | GEO

A reference model for circulating hematopoietic stem cells with applications to diagnostics

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Project description:In physiological conditions, few circulating hematopoietic stem/progenitor cells (cHSPC) are present in peripheral blood (PB) and their role remain unsolved. By integrating advanced immunophenotyping, high-throughput transcriptome profiling and functional assays we characterized the biological properties of human cHSPC. We found distinct composition but comparable bone marrow (BM) homing and differentiation potential after xenotransplantation of cHSPC with respect to their BM counterpart. Trafficking HSPC are in a low-cycling pre-activated state with primitive and committed progenitors being transcriptionally and functionally skewed towards erythroid differentiation. Moreover, a subset of circulating lymphoid progenitors are primed for seeding lymphoid organs and can actively contribute to T-cell production in patients treated with gene therapy. In case of hematopoietic impairment, cHSPC content and composition correlate with BM-HSPC state. Altogether, our data unveiled the cHSPC contribution to steady-state hematopoiesis, with a key function in sustaining extramedullary lympho- and erythro-poiesis, and supported their clinical exploitation as biomarker for BM-HSPC.

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