Single-cell time series analysis reveals the dynamics of in vivo HSPC responses to inflammation

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 of HSPCs during the sensing, response and recovery phases of the inflammatory response of HSPCs to treatment with the pro-inflammatory cytokine IFN to investigate the HSPCs dynamic changes during acute inflammation. For the analysis of the resulting datasets, we developed a computational pipeline for single-cell time series. Using a semi-supervised response-pseudotime inference approach, we discover a variety of different gene responses of the HSPCs to the treatment. Interestingly, we were able to associate reduced myeloid differentiation programs in HSPCs with reduced myeloid progenitor and differentiated cells following IFN treatment. Altogether, single-cell time series analysis have allowed us to unbiasedly study the heterogeneous and dynamic impact of IFN on the HSPCs.