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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 |
| 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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