Single-cell time series analysis reveals the dynamics of HSPC response to inflammation


  • B.J. Bouman
  • Y. Demerdash
  • S. Sood
  • F. Grünschläger
  • F. Pilz
  • A.R. Itani
  • A. Kuck
  • V. Marot-Lassauzaie
  • S. Haas
  • L. Haghverdi
  • M.A. Essers


  • Life Science Alliance


  • Life Sci Alliance 7 (3): e202302309


  • 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.