Journal Article

DKFZ-2023-02768

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Single-cell time series analysis reveals the dynamics of HSPC response to inflammation.

Bouman, B. J. ; Demerdash, Y. (First author)DKFZ* ; Sood, S.DKFZ* ; Grünschläger, F.DKFZ* ; Pilz, F.DKFZ* ; Itani, A. R.DKFZ* ; Kuck, A.DKFZ* ; Marot-Lassauzaie, V. ; Haas, S.DKFZ* ; Haghverdi, L. ; Essers, M. (Last author)DKFZ*

2023
EMBO Press Heidelberg

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Please use a persistent id in citations: doi:10.26508/lsa.202302309

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 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.

Keyword(s): Humans (MeSH) ; Time Factors (MeSH) ; Hematopoietic Stem Cells (MeSH) ; Cell Differentiation: genetics (MeSH) ; Hematopoiesis: genetics (MeSH) ; Inflammation: metabolism (MeSH)

Note: DKFZ–ZMBH Alliance / #EA:A011#LA:A011#

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Contributing Institute(s):

1. A011 Stressinduzierte Aktivierung von Hämatopeotischen Stammzellen (A011)
2. A010 Stammzellen und Krebs (A010)
3. DKTK Koordinierungsstelle Berlin (BE01)

Research Program(s):

1. 311 - Zellbiologie und Tumorbiologie (POF4-311) (POF4-311)

Appears in the scientific report 2023

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