Show simple item record

dc.contributor.author
Zanotelli, Vito R.T.
dc.contributor.author
Leutenegger, Matthias
dc.contributor.author
Lun, Xiao-Kang
dc.contributor.author
Georgi, Fanny
dc.contributor.author
de Souza, Natalie
dc.contributor.author
Bodenmiller, Bernd
dc.date.accessioned
2021-01-27T16:28:49Z
dc.date.available
2021-01-03T03:36:38Z
dc.date.available
2021-01-13T19:30:56Z
dc.date.available
2021-01-27T16:28:49Z
dc.date.issued
2020-12-01
dc.identifier.issn
1744-4292
dc.identifier.other
10.15252/msb.20209798
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/458851
dc.identifier.doi
10.3929/ethz-b-000458851
dc.description.abstract
Cells react to their microenvironment by integrating external stimuli into phenotypic decisions via an intracellular signaling network. To analyze the interplay of environment, local neighborhood, and internal cell state effects on phenotypic variability, we developed an experimental approach that enables multiplexed mass cytometric imaging analysis of up to 240 pooled spheroid microtissues. We quantified the contributions of environment, neighborhood, and intracellular state to marker variability in single cells of the spheroids. A linear model explained on average more than half of the variability of 34 markers across four cell lines and six growth conditions. The contributions of cell‐intrinsic and environmental factors to marker variability are hierarchically interdependent, a finding that we propose has general implications for systems‐level studies of single‐cell phenotypic variability. By the overexpression of 51 signaling protein constructs in subsets of cells, we also identified proteins that have cell‐intrinsic and cell‐extrinsic effects. Our study deconvolves factors influencing cellular phenotype in a 3D tissue and provides a scalable experimental system, analytical principles, and rich multiplexed imaging datasets for future studies.
en_US
dc.format
application/pdf
en_US
dc.language.iso
en
en_US
dc.publisher
EMBO Press
en_US
dc.rights.uri
http://creativecommons.org/licenses/by/4.0/
dc.subject
high-throughput assay
en_US
dc.subject
multiplexed imaging
en_US
dc.subject
spatial signaling
en_US
dc.subject
spatial variance
en_US
dc.subject
tissue organization
en_US
dc.title
A quantitative analysis of the interplay of environment, neighborhood, and cell state in 3D spheroids
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution 4.0 International
dc.date.published
2020-12-26
ethz.journal.title
Molecular Systems Biology
ethz.journal.volume
16
en_US
ethz.journal.issue
12
en_US
ethz.journal.abbreviated
Mol Syst Biol
ethz.pages.start
e9798
en_US
ethz.size
21 p.
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.identifier.wos
ethz.identifier.scopus
ethz.publication.place
Heidelberg
en_US
ethz.publication.status
published
en_US
ethz.leitzahl
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02030 - Dep. Biologie / Dep. of Biology::02539 - Institut für Molecular Health Sciences / Institute of Molecular Health Sciences::09735 - Bodenmiller, Bernd / Bodenmiller, Bernd
ethz.leitzahl.certified
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02030 - Dep. Biologie / Dep. of Biology::02539 - Institut für Molecular Health Sciences / Institute of Molecular Health Sciences::09735 - Bodenmiller, Bernd / Bodenmiller, Bernd
ethz.date.deposited
2021-01-03T03:36:42Z
ethz.source
SCOPUS
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2021-01-13T19:31:20Z
ethz.rosetta.lastUpdated
2022-03-29T04:59:27Z
ethz.rosetta.versionExported
true
ethz.COinS
ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.atitle=A%20quantitative%20analysis%20of%20the%20interplay%20of%20environment,%20neighborhood,%20and%20cell%20state%20in%203D%20spheroids&rft.jtitle=Molecular%20Systems%20Biology&rft.date=2020-12-01&rft.volume=16&rft.issue=12&rft.spage=e9798&rft.issn=1744-4292&rft.au=Zanotelli,%20Vito%20R.T.&Leutenegger,%20Matthias&Lun,%20Xiao-Kang&Georgi,%20Fanny&de%20Souza,%20Natalie&rft.genre=article&rft_id=info:doi/10.15252/msb.20209798&
 Search print copy at ETH Library

Files in this item

Thumbnail

Publication type

Show simple item record