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082 _ _ |a 570
100 1 _ |a Bouman, Brigitte J
|b 0
245 _ _ |a Single-cell time series analysis reveals the dynamics of HSPC response to inflammation.
260 _ _ |a Heidelberg
|b EMBO Press
|c 2023
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520 _ _ |a 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.
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650 _ 2 |2 MeSH
|a Humans
650 _ 2 |2 MeSH
|a Time Factors
650 _ 2 |2 MeSH
|a Hematopoietic Stem Cells
650 _ 2 |2 MeSH
|a Cell Differentiation: genetics
650 _ 2 |2 MeSH
|a Hematopoiesis: genetics
650 _ 2 |2 MeSH
|a Inflammation: metabolism
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|a Demerdash, Yasmin
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