Dataset Information

Population context drives cell-to-cell variability in interferon response in epithelial cells

ABSTRACT: Isogenic cells respond in a heterogeneous manner to interferon. Using a micropatterning approach combined with high-content imaging and spatial analyses, we characterized how the population context (position of a cell with respect to neighboring cells) of epithelial cells affects single cell response to interferons. We identified that cells at the edge of cellular colonies are more responsive than cells embedded within colonies. We determined that this spatial heterogeneity in interferon response resulted from the polarized basolateral interferon receptor distribution, making cells located in the center of cellular colonies less responsive to ectopic interferon stimulation. This was conserved across cell lines and primary cells originated from epithelial tissues. Finally, we demonstrated that this population context-driven cell-to-cell variability influences the outcome of viral infection, as cells embedded within cellular colonies are not protected by interferons and therefore more susceptible to infection. Our data highlights that the behavior of isolated cells does not directly translate to their behavior in a population, placing the population context as one important factor influencing cell-to-cell heterogeneity during interferon response in epithelial cells.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epithelial Cell, Colon

DISEASE(S): Colon Cancer

SUBMITTER: Benno Kuropka

LAB HEAD: Steeve Boulant

PROVIDER: PXD047936 | Pride | 2024-02-07

REPOSITORIES: Pride

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			Action	DRS
	2020-08-13_QE_BK194_FM_Surface_Prot_Apical_01.raw	Raw
	2020-08-13_QE_BK194_FM_Surface_Prot_Apical_02.raw	Raw
	2020-08-13_QE_BK194_FM_Surface_Prot_Apical_03.raw	Raw
	2020-08-13_QE_BK194_FM_Surface_Prot_Apical_04.raw	Raw
	2020-08-13_QE_BK194_FM_Surface_Prot_Apical_05.raw	Raw

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The population context is a driver of the heterogeneous response of epithelial cells to interferons.

Metz-Zumaran Camila C Uckeley Zina M ZM Doldan Patricio P Muraca Francesco F Keser Yagmur Y Lukas Pascal P Kuropka Benno B Küchenhoff Leonie L Rastgou Talemi Soheil S Höfer Thomas T Freund Christian C Cavalcanti-Adam Elisabetta Ada EA Graw Frederik F Stanifer Megan M Boulant Steeve S

Molecular systems biology 20240125 3

Isogenic cells respond in a heterogeneous manner to interferon. Using a micropatterning approach combined with high-content imaging and spatial analyses, we characterized how the population context (position of a cell with respect to neighboring cells) of epithelial cells affects their response to interferons. We identified that cells at the edge of cellular colonies are more responsive than cells embedded within colonies. We determined that this spatial heterogeneity in interferon response resu ...[more]

PMID: 38273161

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