Spatially exploring RNA biology in archival formalin-fixed paraffin-embedded tissues.

RNA biology clinical FFPE tissue histopathology microRNA single-nucleotide RNA variants spatial omics spatiotemporal dynamics splicing isoforms whole transcriptome

Journal

Cell
ISSN: 1097-4172
Titre abrégé: Cell
Pays: United States
ID NLM: 0413066

Informations de publication

Date de publication:
25 Sep 2024
Historique:
received: 02 02 2024
revised: 29 07 2024
accepted: 03 09 2024
medline: 3 10 2024
pubmed: 3 10 2024
entrez: 1 10 2024
Statut: aheadofprint

Résumé

The capability to spatially explore RNA biology in formalin-fixed paraffin-embedded (FFPE) tissues holds transformative potential for histopathology research. Here, we present pathology-compatible deterministic barcoding in tissue (Patho-DBiT) by combining in situ polyadenylation and computational innovation for spatial whole transcriptome sequencing, tailored to probe the diverse RNA species in clinically archived FFPE samples. It permits spatial co-profiling of gene expression and RNA processing, unveiling region-specific splicing isoforms, and high-sensitivity transcriptomic mapping of clinical tumor FFPE tissues stored for 5 years. Furthermore, genome-wide single-nucleotide RNA variants can be captured to distinguish malignant subclones from non-malignant cells in human lymphomas. Patho-DBiT also maps microRNA regulatory networks and RNA splicing dynamics, decoding their roles in spatial tumorigenesis. Single-cell level Patho-DBiT dissects the spatiotemporal cellular dynamics driving tumor clonal architecture and progression. Patho-DBiT stands poised as a valuable platform to unravel rich RNA biology in FFPE tissues to aid in clinical pathology evaluation.

Identifiants

DOI: 10.1016/j.cell.2024.09.001 PMID: 39353436
pubmed: 39353436
pii: S0092-8674(24)01019-5
doi: 10.1016/j.cell.2024.09.001
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests Z.B. and R.F. are inventors of a patent application related to this work. R.F. is scientific founder and adviser for IsoPlexis, Singleron Biotechnologies, and AtlasXomics. The interests of R.F. were reviewed and managed by Yale University Provost’s Office in accordance with the University’s conflict of interest policies. M.L.X. has served as consultant for Treeline Biosciences, Pure Marrow, and Seattle Genetics. Daiwei Zhang and M.L. are co-founders or OmicPath AI LLC. M.L. receives research funding from Biogen Inc. unrelated to the current manuscript.

Auteurs

Zhiliang Bai (Z)

Department of Biomedical Engineering, Yale University, New Haven, CT 06520, USA. Electronic address: zhiliang.bai@yale.edu.

Dingyao Zhang (D)

Department of Genetics, Yale University School of Medicine, New Haven, CT 06520, USA; Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT 06520, USA.

Yan Gao (Y)

Center for Computational and Genomic Medicine, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.

Bo Tao (B)

Department of Pathology, Yale University School of Medicine, New Haven, CT 06520, USA.

Daiwei Zhang (D)

Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

Shuozhen Bao (S)

Department of Biomedical Engineering, Yale University, New Haven, CT 06520, USA.

Archibald Enninful (A)

Department of Biomedical Engineering, Yale University, New Haven, CT 06520, USA.

Yadong Wang (Y)

Department of Genetics, Yale University School of Medicine, New Haven, CT 06520, USA.

Haikuo Li (H)

Department of Biomedical Engineering, Yale University, New Haven, CT 06520, USA.

Graham Su (G)

Department of Biomedical Engineering, Yale University, New Haven, CT 06520, USA.

Xiaolong Tian (X)

Department of Biomedical Engineering, Yale University, New Haven, CT 06520, USA.

Ningning Zhang (N)

Department of Genetics, Yale University School of Medicine, New Haven, CT 06520, USA.

Yang Xiao (Y)

Department of Biomedical Engineering, Columbia University, New York, NY 10027, USA.

Yang Liu (Y)

Department of Pathology, Yale University School of Medicine, New Haven, CT 06520, USA.

Mark Gerstein (M)

Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT 06520, USA.

Mingyao Li (M)

Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: mingyao@pennmedicine.upenn.edu.

Yi Xing (Y)

Center for Computational and Genomic Medicine, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: xingyi@chop.edu.

Jun Lu (J)

Department of Genetics, Yale University School of Medicine, New Haven, CT 06520, USA; Yale Stem Cell Center and Yale Cancer Center, Yale University School of Medicine, New Haven, CT 06520, USA. Electronic address: jun.lu@yale.edu.

Mina L Xu (ML)

Department of Pathology, Yale University School of Medicine, New Haven, CT 06520, USA. Electronic address: mina.xu@yale.edu.

Rong Fan (R)

Department of Biomedical Engineering, Yale University, New Haven, CT 06520, USA; Department of Pathology, Yale University School of Medicine, New Haven, CT 06520, USA; Yale Stem Cell Center and Yale Cancer Center, Yale University School of Medicine, New Haven, CT 06520, USA; Human and Translational Immunology, Yale University School of Medicine, New Haven, CT 06520, USA. Electronic address: rong.fan@yale.edu.

Classifications MeSH