Single-cell time series analysis reveals the dynamics of HSPC response to inflammation.

Autor:	Bouman BJ; Berlin Institute for Medical Systems Biology, Max Delbrück Center in the Helmholtz Association, Berlin, Germany.; Institute for Biology, Humboldt-Universität zu Berlin, Berlin, Germany., Demerdash Y; Division Inflammatory Stress in Stem Cells, German Cancer Research Center (DKFZ), Heidelberg, Germany.; Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGMBH), Heidelberg, Germany.; Faculty of Biosciences, University of Heidelberg, Heidelberg, Germany., Sood S; Division Inflammatory Stress in Stem Cells, German Cancer Research Center (DKFZ), Heidelberg, Germany.; Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGMBH), Heidelberg, Germany.; Faculty of Biosciences, University of Heidelberg, Heidelberg, Germany., Grünschläger F; Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGMBH), Heidelberg, Germany.; Faculty of Biosciences, University of Heidelberg, Heidelberg, Germany.; Division of Stem Cells and Cancer, Deutsches Krebsforschungszentrum (DKFZ) and DKFZ-ZMBH Alliance, Heidelberg, Germany., Pilz F; Division Inflammatory Stress in Stem Cells, German Cancer Research Center (DKFZ), Heidelberg, Germany.; Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGMBH), Heidelberg, Germany., Itani AR; Division Inflammatory Stress in Stem Cells, German Cancer Research Center (DKFZ), Heidelberg, Germany.; Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGMBH), Heidelberg, Germany.; Faculty of Biosciences, University of Heidelberg, Heidelberg, Germany., Kuck A; Division Inflammatory Stress in Stem Cells, German Cancer Research Center (DKFZ), Heidelberg, Germany.; Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGMBH), Heidelberg, Germany., Marot-Lassauzaie V; Berlin Institute for Medical Systems Biology, Max Delbrück Center in the Helmholtz Association, Berlin, Germany.; Charité-Universitätsmedizin, Berlin, Germany., Haas S; Berlin Institute for Medical Systems Biology, Max Delbrück Center in the Helmholtz Association, Berlin, Germany.; Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGMBH), Heidelberg, Germany.; Department of Hematology, Oncology and Cancer Immunology, Campus Benjamin Franklin, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.; German Cancer Consortium (DKTK), Heidelberg, Germany.; Berlin Institute of Health (BIH) at Charité - Universitätsmedizin Berlin, Berlin, Germany.; Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany.; Charité-Universitätsmedizin, Berlin, Germany., Haghverdi L; Berlin Institute for Medical Systems Biology, Max Delbrück Center in the Helmholtz Association, Berlin, Germany Laleh.Haghverdi@mdc-berlin.de., Essers MA; Division Inflammatory Stress in Stem Cells, German Cancer Research Center (DKFZ), Heidelberg, Germany m.essers@dkfz-heidelberg.de.; Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGMBH), Heidelberg, Germany.; DKFZ-ZMBH Alliance, Heidelberg, Germany.
Jazyk:	angličtina
Zdroj:	Life science alliance [Life Sci Alliance] 2023 Dec 18; Vol. 7 (3). Date of Electronic Publication: 2023 Dec 18 (Print Publication: 2024).
DOI:	10.26508/lsa.202302309
Abstrakt:	Hematopoietic stem and progenitor cells (HSPCs) are known to respond to acute inflammation; however, little is understood about the dynamics and heterogeneity of these stress responses in HSPCs. Here, we performed single-cell sequencing during the sensing, response, and recovery phases of the inflammatory response of HSPCs to treatment (a total of 10,046 cells from four time points spanning the first 72 h of response) with the pro-inflammatory cytokine IFNα to investigate the HSPCs' dynamic changes during acute inflammation. We developed the essential novel computational approaches to process and analyze the resulting single-cell time series dataset. This includes an unbiased cell type annotation and abundance analysis post inflammation, tools for identification of global and cell type-specific responding genes, and a semi-supervised linear regression approach for response pseudotime reconstruction. We discovered a variety of different gene responses of the HSPCs to the treatment. Interestingly, we were able to associate a global reduced myeloid differentiation program and a locally enhanced pyroptosis activity with reduced myeloid progenitor and differentiated cells after IFNα treatment. Altogether, the single-cell time series analyses have allowed us to unbiasedly study the heterogeneous and dynamic impact of IFNα on the HSPCs. (© 2023 Bouman et al.)
Databáze:	MEDLINE
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