%0 Journal Article
%A Bouman, Brigitte J
%A Demerdash, Yasmin
%A Sood, Shubhankar
%A Grünschläger, Florian
%A Pilz, Franziska
%A Itani, Abdul Rahman
%A Kuck, Andrea
%A Marot-Lassauzaie, Valérie
%A Haas, Simon
%A Haghverdi, Laleh
%A Essers, Marieke
%T Single-cell time series analysis reveals the dynamics of HSPC response to inflammation.
%J Life science alliance
%V 7
%N 3
%@ 2575-1077
%C Heidelberg
%I EMBO Press
%M DKFZ-2023-02768
%P e202302309
%D 2023
%Z DKFZ–ZMBH Alliance / #EA:A011#LA:A011#
%X 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.
%K Humans
%K Time Factors
%K Hematopoietic Stem Cells
%K Cell Differentiation: genetics
%K Hematopoiesis: genetics
%K Inflammation: metabolism
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:38110222
%R 10.26508/lsa.202302309
%U https://inrepo02.dkfz.de/record/286281