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| Item Type: | Article |
|---|---|
| Title: | Single-cell time series analysis reveals the dynamics of HSPC response to inflammation |
| Creators: |
Bouman, B.J.  ORCID: https://orcid.org/0000-0003-1259-5040, Demerdash, Y., Sood, S., Grünschläger, F., Pilz, F., Itani, A.R. ORCID: https://orcid.org/0000-0001-7608-822X, Kuck, A., Marot-Lassauzaie, V. ORCID: https://orcid.org/0000-0002-8362-9634, Haas, S. ORCID: https://orcid.org/0000-0001-9227-2051, Haghverdi, L. ORCID: https://orcid.org/0000-0001-9280-9170 and Essers, M.A. ORCID: https://orcid.org/0000-0003-3117-1809
|
| 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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