TY  - JOUR
AU  - Bouman, Brigitte J
AU  - Demerdash, Yasmin
AU  - Sood, Shubhankar
AU  - Grünschläger, Florian
AU  - Pilz, Franziska
AU  - Itani, Abdul Rahman
AU  - Kuck, Andrea
AU  - Marot-Lassauzaie, Valérie
AU  - Haas, Simon
AU  - Haghverdi, Laleh
AU  - Essers, Marieke
TI  - Single-cell time series analysis reveals the dynamics of HSPC response to inflammation.
JO  - Life science alliance
VL  - 7
IS  - 3
SN  - 2575-1077
CY  - Heidelberg
PB  - EMBO Press
M1  - DKFZ-2023-02768
SP  - e202302309
PY  - 2023
N1  - DKFZ–ZMBH Alliance / #EA:A011#LA:A011#
AB  - 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.
KW  - Humans
KW  - Time Factors
KW  - Hematopoietic Stem Cells
KW  - Cell Differentiation: genetics
KW  - Hematopoiesis: genetics
KW  - Inflammation: metabolism
LB  - PUB:(DE-HGF)16
C6  - pmid:38110222
DO  - DOI:10.26508/lsa.202302309
UR  - https://inrepo02.dkfz.de/record/286281
ER  -