| First Author | Bouman BJ | Year | 2024 |
| Journal | Life Sci Alliance | Volume | 7 |
| Issue | 3 | PubMed ID | 38110222 |
| Mgi Jnum | J:348953 | Mgi Id | MGI:7568337 |
| Doi | 10.26508/lsa.202302309 | Citation | Bouman BJ, et al. (2024) Single-cell time series analysis reveals the dynamics of HSPC response to inflammation. Life Sci Alliance 7(3) |
| abstractText | 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 IFNalpha 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 IFNalpha treatment. Altogether, the single-cell time series analyses have allowed us to unbiasedly study the heterogeneous and dynamic impact of IFNalpha on the HSPCs. |
