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000286281 1001_ $$aBouman, Brigitte J$$b0
000286281 245__ $$aSingle-cell time series analysis reveals the dynamics of HSPC response to inflammation.
000286281 260__ $$aHeidelberg$$bEMBO Press$$c2023
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000286281 520__ $$aHematopoietic stem and progenitor cells (HSPCs) are known to respond to acute inflammation; however, little is understood about the dynamics and heterogeneity of these stress responses in HSPCs. Here, we performed single-cell sequencing during the sensing, response, and recovery phases of the inflammatory response of HSPCs to treatment (a total of 10,046 cells from four time points spanning the first 72 h of response) with the pro-inflammatory cytokine IFNα to investigate the HSPCs' dynamic changes during acute inflammation. We developed the essential novel computational approaches to process and analyze the resulting single-cell time series dataset. This includes an unbiased cell type annotation and abundance analysis post inflammation, tools for identification of global and cell type-specific responding genes, and a semi-supervised linear regression approach for response pseudotime reconstruction. We discovered a variety of different gene responses of the HSPCs to the treatment. Interestingly, we were able to associate a global reduced myeloid differentiation program and a locally enhanced pyroptosis activity with reduced myeloid progenitor and differentiated cells after IFNα treatment. Altogether, the single-cell time series analyses have allowed us to unbiasedly study the heterogeneous and dynamic impact of IFNα on the HSPCs.
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000286281 650_2 $$2MeSH$$aHumans
000286281 650_2 $$2MeSH$$aTime Factors
000286281 650_2 $$2MeSH$$aHematopoietic Stem Cells
000286281 650_2 $$2MeSH$$aCell Differentiation: genetics
000286281 650_2 $$2MeSH$$aHematopoiesis: genetics
000286281 650_2 $$2MeSH$$aInflammation: metabolism
000286281 7001_ $$0P:(DE-He78)5dd8fe881be96755fdff6576c9f8c11f$$aDemerdash, Yasmin$$b1$$eFirst author$$udkfz
000286281 7001_ $$0P:(DE-He78)dbe2fd9578ec0bf59e0e17592b04f22f$$aSood, Shubhankar$$b2$$udkfz
000286281 7001_ $$0P:(DE-He78)6b879b5f67d8b3bcdffc7c01cbf8d1f1$$aGrünschläger, Florian$$b3$$udkfz
000286281 7001_ $$0P:(DE-He78)fc5931eb2c72c84c56b289eeedc6758c$$aPilz, Franziska$$b4$$udkfz
000286281 7001_ $$0P:(DE-He78)95e6d7666dcf19dcfa2b9a9a6ada3d86$$aItani, Abdul Rahman$$b5$$udkfz
000286281 7001_ $$0P:(DE-He78)fa2049c5d1b3a53b145d94b5830b3c47$$aKuck, Andrea$$b6$$udkfz
000286281 7001_ $$00000-0002-8362-9634$$aMarot-Lassauzaie, Valérie$$b7
000286281 7001_ $$0P:(DE-He78)a5ec4e2fef99022a37a6b07c2fdd6325$$aHaas, Simon$$b8$$udkfz
000286281 7001_ $$00000-0001-9280-9170$$aHaghverdi, Laleh$$b9
000286281 7001_ $$0P:(DE-He78)ba3fae49054b6bfaaa289b05ecd936d6$$aEssers, Marieke$$b10$$eLast author$$udkfz
000286281 773__ $$0PERI:(DE-600)2948687-7$$a10.26508/lsa.202302309$$gVol. 7, no. 3, p. e202302309 -$$n3$$pe202302309$$tLife science alliance$$v7$$x2575-1077$$y2024
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