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

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Item Type:Article
Title:Single-cell time series analysis reveals the dynamics of HSPC response to inflammation
Creators Name:Bouman, B.J. and Demerdash, Y. and Sood, S. and Grünschläger, F. and Pilz, F. and Itani, A.R. and Kuck, A. and Marot-Lassauzaie, V. and Haas, S. and Haghverdi, L. and Essers, M.A.
Abstract: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.
Keywords:Cell Differentiation, Hematopoiesis, Hematopoietic Stem Cells*, Inflammation, Time Factors
Source:Life Science Alliance
Publisher:Life Science Alliance
Page Range:e202302309
Date:March 2024
Official Publication:https://doi.org/10.26508/lsa.202302309
PubMed:View item in PubMed

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