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

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 inflam...

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Main Authors: Bouman, Brigitte J. (Author) , Demerdash, Yasmin (Author) , Sood, Shubhankar (Author) , Grünschläger, Florian (Author) , Pilz, Franziska (Author) , Itani, Abdul Rahman (Author) , Kuck, Andrea (Author) , Marot-Lassauzaie, Valérie (Author) , Haas, Simon (Author) , Haghverdi, Laleh (Author) , Essers, Marieke (Author)
Format: Article (Journal)
Language:English
Published: March 2024
In: Life science alliance
Year: 2024, Volume: 7, Issue: 3, Pages: 1-17
ISSN:2575-1077
DOI:10.26508/lsa.202302309
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.26508/lsa.202302309
Verlag, lizenzpflichtig, Volltext: https://www.life-science-alliance.org/content/7/3/e202302309
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Author Notes:Brigitte J. Bouman, Yasmin Demerdash, Shubhankar Sood, Florian Grünschläger, Franziska Pilz, Abdul R Itani, Andrea Kuck, Valérie Marot-Lassauzaie, Simon Haas, Laleh Haghverdi, Marieke AG Essers
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Summary: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 proinflammatory cytokine IFN alpha 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 IFN alpha treatment. Altogether, the single-cell time series analyses have allowed us to unbiasedly study the heterogeneous and dynamic impact of IFN alpha on the HSPCs.
Item Description:Gesehen am 03.12.2024
Online veröffentlicht: 18. Dezember 2023
Physical Description:Online Resource
ISSN:2575-1077
DOI:10.26508/lsa.202302309

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