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Item Type: | Article |
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Title: | Single-cell time series analysis reveals the dynamics of HSPC response to inflammation |
Creators Name: | Bouman, B.J., Demerdash, Y., Sood, S., Grünschläger, F., Pilz, F., Itani, A.R., Kuck, A., Marot-Lassauzaie, V., Haas, S., 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 |
ISSN: | 2575-1077 |
Publisher: | Life Science Alliance |
Volume: | 7 |
Number: | 3 |
Page Range: | e202302309 |
Date: | March 2024 |
Official Publication: | https://doi.org/10.26508/lsa.202302309 |
PubMed: | View item in PubMed |
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