Positional influence on cellular transcriptional identity revealed through spatially segmented single-cell transcriptomics.

Transcriptome / genetics Gene Expression Profiling Kinetics Organoids Physics
RNA sequencing genomics oncology ovarian cancer scRNA-seq single-cell transcriptomics spatial transcriptomics spatially resolved transcriptomics

Journal

Cell systems
ISSN: 2405-4720
Titre abrégé: Cell Syst
Pays: United States
ID NLM: 101656080

Informations de publication

Date de publication:
21 06 2023
Historique:
received: 29 12 2021
revised: 22 01 2023
accepted: 17 05 2023
medline: 26 6 2023
pubmed: 23 6 2023
entrez: 22 6 2023
Statut: ppublish

Résumé

Single-cell RNA sequencing (scRNA-seq) is a powerful technique for describing cell states. Identifying the spatial arrangement of these states in tissues remains challenging, with the existing methods requiring niche methodologies and expertise. Here, we describe segmentation by exogenous perfusion (SEEP), a rapid and integrated method to link surface proximity and environment accessibility to transcriptional identity within three-dimensional (3D) disease models. The method utilizes the steady-state diffusion kinetics of a fluorescent dye to establish a gradient along the radial axis of disease models. Classification of sample layers based on dye accessibility enables dissociated and sorted cells to be characterized by transcriptomic and regional identities. Using SEEP, we analyze spheroid, organoid, and in vivo tumor models of high-grade serous ovarian cancer (HGSOC). The results validate long-standing beliefs about the relationship between cell state and position while revealing new concepts regarding how spatially unique microenvironments influence the identity of individual cells within tumors.

Identifiants

DOI: 10.1016/j.cels.2023.05.003 PMID: 37348462 PMC: PMC10424188
pubmed: 37348462
pii: S2405-4712(23)00147-3
doi: 10.1016/j.cels.2023.05.003
pmc: PMC10424188
mid: NIHMS1904912
pii:
doi:

Types de publication

Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Langues

eng

Sous-ensembles de citation

IM

Pagination

464-481.e7

Subventions

Organisme : Intramural NIH HHS
ID : Z99 TR999999
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM007753
Pays : United States
Organisme : Cancer Research UK
ID : 15601
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Cancer Research UK
ID : 22905
Pays : United Kingdom

Informations de copyright

Published by Elsevier Inc.

Déclaration de conflit d'intérêts

Declaration of interests The authors declare no competing interests.

Références

Gynecol Oncol. 2019 Jul;154(1):189-198
pubmed: 31101504
Science. 2016 Jul 1;353(6294):78-82
pubmed: 27365449
Nat Protoc. 2017 Jan;12(1):44-73
pubmed: 27929523
Nat Genet. 2018 Sep;50(9):1262-1270
pubmed: 30104763
PLoS One. 2014 Sep 17;9(9):e103988
pubmed: 25230021
Front Oncol. 2013 Sep 25;3:256
pubmed: 24093089
Nat Methods. 2012 Jul;9(7):671-5
pubmed: 22930834
J Immunol Methods. 1995 Jan 13;178(1):41-51
pubmed: 7829864
Cell Death Dis. 2016 Dec 1;7(12):e2492
pubmed: 27906188
Science. 2015 Apr 24;348(6233):aaa6090
pubmed: 25858977
Science. 2019 Mar 29;363(6434):1463-1467
pubmed: 30923225
Cell. 2015 May 21;161(5):1202-1214
pubmed: 26000488
Bioinformatics. 2020 Apr 1;36(7):2311-2313
pubmed: 31764967
J Clin Invest. 2014 Jun;124(6):2611-25
pubmed: 24762435
ACS Chem Biol. 2022 Feb 18;17(2):281-291
pubmed: 35026106
Nat Cell Biol. 2012 Apr 02;14(4):332
pubmed: 22469826
Nature. 2011 Jun 29;474(7353):609-15
pubmed: 21720365
IEEE Trans Pattern Anal Mach Intell. 2020 Feb;42(2):386-397
pubmed: 29994331
Bioinformatics. 2011 Jun 15;27(12):1739-40
pubmed: 21546393
Comput Struct Biotechnol J. 2021 Jun 30;19:3796-3798
pubmed: 34285779
Nat Med. 2011 Oct 30;17(11):1498-503
pubmed: 22037646
N Engl J Med. 2012 Mar 8;366(10):883-892
pubmed: 22397650
J Immunol Methods. 1990 Oct 4;133(1):87-97
pubmed: 2212694
Nat Rev Dis Primers. 2016 Aug 25;2:16061
pubmed: 27558151
Stem Cell Reports. 2020 Apr 14;14(4):717-729
pubmed: 32243841
Gynecol Oncol. 2011 Sep;122(3):656-62
pubmed: 21676452
Cell. 2021 Jun 24;184(13):3573-3587.e29
pubmed: 34062119
Mol Pharm. 2014 Jul 7;11(7):2071-81
pubmed: 24641346
Clin Cancer Res. 2018 Oct 15;24(20):5037-5047
pubmed: 30084834
Biotechniques. 2016 Nov 1;61(5):237-247
pubmed: 27839509
Nat Methods. 2017 Nov;14(11):1083-1086
pubmed: 28991892
Assay Drug Dev Technol. 2014 May;12(4):207-18
pubmed: 24831787
Math Biosci. 2014 Dec;258:33-43
pubmed: 25245610
Science. 2014 Mar 21;343(6177):1360-3
pubmed: 24578530
Sci Rep. 2018 Aug 17;8(1):12394
pubmed: 30120290
Cold Spring Harb Symp Quant Biol. 2005;70:343-56
pubmed: 16869771
Proc Natl Acad Sci U S A. 2021 Jun 1;118(22):
pubmed: 34001664
Nat Med. 2020 Aug;26(8):1271-1279
pubmed: 32572264
Nat Med. 2019 May;25(5):838-849
pubmed: 31011202
Nat Biotechnol. 2018 Jun;36(5):411-420
pubmed: 29608179
Nat Methods. 2013 Sep;10(9):857-60
pubmed: 23852452
Cell Syst. 2015 Dec 23;1(6):417-425
pubmed: 26771021
Nature. 2017 Feb 16;542(7641):352-356
pubmed: 28166538
Trends Biotechnol. 2013 Feb;31(2):108-15
pubmed: 23336996
Nat Genet. 2003 Jul;34(3):267-73
pubmed: 12808457
Nat Biotechnol. 2020 May;38(5):586-599
pubmed: 32393914
Nat Commun. 2019 Nov 26;10(1):5367
pubmed: 31772167
Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15545-50
pubmed: 16199517
Cancer Discov. 2011 Jul;1(2):144-57
pubmed: 22303516
Int J Cancer. 1987 Jun 15;39(6):695-702
pubmed: 3583449
Nat Rev Cancer. 2018 Jul;18(7):407-418
pubmed: 29692415
Bioinformatics. 2017 Apr 15;33(8):1179-1186
pubmed: 28088763
Nature. 2002 Dec 19-26;420(6917):860-7
pubmed: 12490959
BMC Bioinformatics. 2013 Jan 16;14:7
pubmed: 23323831
Nat Rev Genet. 2018 Nov;19(11):671-687
pubmed: 30228295
Nat Biotechnol. 2015 May;33(5):503-9
pubmed: 25867922
Cell. 2019 Jun 13;177(7):1888-1902.e21
pubmed: 31178118
Nat Commun. 2019 Jan 21;10(1):360
pubmed: 30664627
Cancer Res. 1988 Nov 1;48(21):6166-72
pubmed: 3167863
Nature. 2019 May;569(7754):66-72
pubmed: 31019299
Am J Pathol. 2010 Sep;177(3):1053-64
pubmed: 20651229
Nat Commun. 2017 Jan 16;8:14049
pubmed: 28091601
Cell. 2015 May 21;161(5):1187-1201
pubmed: 26000487
Nat Methods. 2019 Oct;16(10):987-990
pubmed: 31501547
Science. 2018 Jun 1;360(6392):
pubmed: 29700227
Nat Biotechnol. 2015 May;33(5):495-502
pubmed: 25867923

Auteurs

David B Morse (DB)

Cavendish Laboratory, Department of Physics, University of Cambridge, J J Thomson Ave, Cambridge, UK; Division of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD, USA; John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA.

Aleksandra M Michalowski (AM)

Laboratory of Cancer Biology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

Michele Ceribelli (M)

Division of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD, USA.

Joachim De Jonghe (J)

Department of Biochemistry, University of Cambridge, Cambridge, UK.

Maria Vias (M)

Cancer Research UK, Cambridge Research Institute, Li Ka Shing Centre, Robinson Way, Cambridge, UK.

Deanna Riley (D)

Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

Theresa Davies-Hill (T)

Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

Ty Voss (T)

Division of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD, USA.

Stefania Pittaluga (S)

Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

Christoph Muus (C)

John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA.

Jiamin Liu (J)

Advanced Imaging and Microscopy Resource, National Institutes of Health Clinical Center, Bethesda, MD, USA.

Samantha Boyle (S)

Cancer Research UK, Cambridge Research Institute, Li Ka Shing Centre, Robinson Way, Cambridge, UK.

David A Weitz (DA)

John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, USA; Department of Physics, Harvard University, Cambridge, MA, USA.

James D Brenton (JD)

Cancer Research UK, Cambridge Research Institute, Li Ka Shing Centre, Robinson Way, Cambridge, UK.

Jason D Buenrostro (JD)

Broad Institute of MIT and Harvard, Cambridge, MA, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, USA.

Tuomas P J Knowles (TPJ)

Cavendish Laboratory, Department of Physics, University of Cambridge, J J Thomson Ave, Cambridge, UK; Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, UK. Electronic address: tpjk2@cam.ac.uk.

Craig J Thomas (CJ)

Division of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD, USA; Lymphoid Malignancies Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. Electronic address: craigt@mail.nih.gov.

Articles similaires

Organoids in the oral and maxillofacial region: present and future.

Yufei Wu, Xiang Li, Hanzhe Liu et al.
1.00
Organoids Humans Tissue Engineering Coculture Techniques Regenerative Medicine

Systematical characterization of Rab7 gene family in Gossypium and potential functions of GhRab7B3-A gene in drought tolerance.

Mengyuan Yan, Zhiwei Dong, Tian Pan et al.
1.00
Drought Resistance Gene Expression Profiling Gene Expression Regulation, Plant Gossypium Multigene Family

A cytoplasmic osmosensing mechanism mediated by molecular crowding-sensitive DCP5.

Zhenyu Wang, Qiuhua Yang, Dan Zhang et al.
1.00
Arabidopsis Arabidopsis Proteins Osmotic Pressure Cytoplasm RNA, Messenger

GUCA2A dysregulation as a promising biomarker for accurate diagnosis and prognosis of colorectal cancer.

Pooya Jalali, Shahram Aliyari, Marziyeh Etesami et al.
1.00
Humans Colorectal Neoplasms Biomarkers, Tumor Prognosis Gene Expression Regulation, Neoplastic

Classifications MeSH

questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Transcriptome › Positional influence on cellular...
questionsmedicales.fr › Techniques d'investigation › Techniques génétiques › Analyse de profil d'expression de gènes › Positional influence on cellular...
questionsmedicales.fr › Phénomènes chimiques › Phénomènes biochimiques › Cinétique › Positional influence on cellular...
questionsmedicales.fr › Tissus › Organoïdes › Positional influence on cellular...
questionsmedicales.fr › Disciplines des sciences naturelles › Physique › Positional influence on cellular...