ArticleNature medicine2020
A single-cell and single-nucleus RNA-Seq toolbox for fresh and frozen human tumors.
Erratum issuedAbstract readEvaluation Study
In one paragraph
Article in Nature medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 475 papers.
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475citing papers in PubMed
–field-weighted citation impact
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Who cites it
475 citing papers in PubMed.
- Cambridge Neoadjuvant Cancer of the Prostate (CANCAP03): A Window Study into the Effects of Olaparib ± Degarelix in Primary Prostate Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Trial
- Neoplastic CD3⁺ B cells remodel the DLBCL tumor microenvironment via single-cell and spatial transcriptomics.Cancer biology & therapy · 2026Article
- Single-cell landscape of piglet lung response withVirulence · 2026Article
- The m 6 A writer VIRMA regulates the developmental elimination of retinal astrocytes and retinal vascular integrity maintenance.Neural regeneration research · 2026Article
- DUET-seq: An Open-Source Droplet Platform for High-Fidelity Joint Chromatin and Transcriptome Profiling Reveals Temporal Regulatory Decoupling in Single Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- CpG hypermethylation and WNT/AP-1 cooperativity define the epigenetic landscape and a clinical subgroup of high-risk pediatric adrenocortical carcinoma.Nature communications · 2026Article
- Wound healing in Atlantic spiny dogfish sharks.Scientific reports · 2026Article
- Mapping ovarian cellular and molecular landscape across the lifespan of women: a scoping review.Human reproduction update · 2026Article
- Single-Nucleus Transcriptomes of Lacrimal Gland Adenoid Cystic Carcinoma With Different Growth Patterns.Head & neck · 2026Article
- Distinct single-nucleus RNA-seq changes among non-neuronal cells in ADNC, LATE-NC, and mixed pathologies.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Fusion-driven oncogenic programs shape the immune landscape in translocation renal cell carcinoma.Nature communications · 2026Article
- Intact Cell Dissociation of Formalin-Fixed Paraffin-Embedded Colon Tissue Enhances Cell Recovery and Gene Detection in Single-Cell RNA Sequencing.Cellular and molecular gastroenterology and hepatology · 2026Article
- Spatial and single-nuclei transcriptomics reveals idiosyncratic and generic patterns in papillary and anaplastic thyroid cancers.Molecular oncology · 2026Article
- Single-cell ultra-high-throughput multiplexed chromatin accessibility and gene expression sequencing (SUM-seq).Nature protocols · 2026Review
- Pre-Existing Heterogeneity Predicts Rare Proteostasis-Stress Programs Across Diverse Perturbations.Biology · 2026Article
- Single-nucleus RNA sequencing reveals cell type-specific responses to heat stress in bovine mammary gland.Journal of animal science and biotechnology · 2026Article
- Protocol for minimized-bias profiling of liver and visceral adipose tissue in mice using integrated single-nucleus RNA sequencing.STAR protocols · 2026Article
- Unleashing innovative cross-organ fibrosis therapies by harnessing the omics revolution.JCI insight · 2026Review
- Protocol for isolation of live tumor-infiltrating immune cells from immunocompetent murine brains for high-dimensional profiling.STAR protocols · 2026Article
- Integrated single-nucleus transcriptomic and chromatin accessibility analysis reveals key molecular basis of human testicular aging.Journal of molecular cell biology · 2026Article
415 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
50 authors.
Michal Slyper *Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
Caroline B M Porter *Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
Orr Ashenberg *Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
Julia WaldmanKlarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
Eugene DrokhlyanskyKlarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
Isaac WakiroBroad Institute of Harvard and MIT, Cambridge, MA, USA.
Christopher SmillieKlarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
Gabriela Smith-RosarioKlarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
Jingyi WuBroad Institute of Harvard and MIT, Cambridge, MA, USA.
Danielle DionneKlarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
Sébastien VigneauBroad Institute of Harvard and MIT, Cambridge, MA, USA.
Judit Jané-ValbuenaKlarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
Timothy L TickleKlarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
Sara NapolitanoBroad Institute of Harvard and MIT, Cambridge, MA, USA.
Mei-Ju SuBroad Institute of Harvard and MIT, Cambridge, MA, USA.
Anand G PatelDepartment of Developmental Neurobiology, St Jude Children's Research Hospital, Memphis, TN, USA.ORCID http://orcid.org/0000-0002-1438-8275
Asa KarlstromDepartment of Developmental Neurobiology, St Jude Children's Research Hospital, Memphis, TN, USA.ORCID http://orcid.org/0000-0003-3847-7309
Simon GritschDepartment of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Masashi NomuraDepartment of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0001-6095-7849
Avinash WaghrayCenter for Regenerative Medicine, Massachusetts General Hospital, Boston, MA, USA.
Satyen H GohilBroad Institute of Harvard and MIT, Cambridge, MA, USA.
Alexander M TsankovKlarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
Livnat Jerby-ArnonKlarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
Ofir CohenBroad Institute of Harvard and MIT, Cambridge, MA, USA.
Johanna KlughammerKlarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
Yanay RosenKlarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
Joshua GouldKlarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA, USA.ORCID http://orcid.org/0000-0001-9581-5461
Lan NguyenKlarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
Matan HofreeKlarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
Peter J TramontozziDivision of Thoracic Surgery, Brigham and Women's Hospital, Boston, MA, USA.ORCID http://orcid.org/0000-0002-5540-0111
Bo LiBroad Institute of Harvard and MIT, Cambridge, MA, USA.
Catherine J WuBroad Institute of Harvard and MIT, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-3348-5054
Benjamin IzarBroad Institute of Harvard and MIT, Cambridge, MA, USA.
Rizwan HaqBroad Institute of Harvard and MIT, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-1290-9276
F Stephen HodiDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Charles H YoonDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Aaron N HataCenter for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Suzanne J BakerDepartment of Developmental Neurobiology, St Jude Children's Research Hospital, Memphis, TN, USA.
Mario L SuvàBroad Institute of Harvard and MIT, Cambridge, MA, USA.ORCID http://orcid.org/0000-0001-9898-5351
Raphael BuenoDivision of Thoracic Surgery, Brigham and Women's Hospital, Boston, MA, USA.
Elizabeth H StoverBroad Institute of Harvard and MIT, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-6578-3216
Michael R ClayDepartment of Pathology, St Jude Children's Research Hospital, Memphis, TN, USA.ORCID http://orcid.org/0000-0003-1659-8927
Michael A DyerDepartment of Developmental Neurobiology, St Jude Children's Research Hospital, Memphis, TN, USA.
Natalie B CollinsBroad Institute of Harvard and MIT, Cambridge, MA, USA.
Ursula A MatulonisDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Nikhil WagleBroad Institute of Harvard and MIT, Cambridge, MA, USA.ORCID http://orcid.org/0000-0003-3332-9438
Bruce E JohnsonDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Asaf RotemBroad Institute of Harvard and MIT, Cambridge, MA, USA.
Orit Rozenblatt-RosenKlarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA, USA. orit@broadinstitute.org.ORCID http://orcid.org/0000-0001-6313-3570
Aviv RegevKlarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA, USA. aregev@broadinstitute.org.ORCID http://orcid.org/0000-0003-3293-3158
Funding
Pilot & Feasibility ProgramP30DK043351 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI Mark Joseph Daly · 1991 to 2026
$35.3MInvestigating Human Adipocyte HeterogeneityRC2DK116691 · NIDDK · BETH ISRAEL DEACONESS MEDICAL CENTER · PI Orr Ashenberg, Noel P Burtt · 2018 to 2026
$17.8MThe Cellular Geography of Therapeutic Resistance in CancerU2CCA233195 · NCI · DANA-FARBER CANCER INST · PI JOHNSON, BRUCE E. · 2018 to 2023
$13.7MThe LungMAP Data Coordination Center for Next Gen Systems Biology of RespirationU24HL148865 · NHLBI · CINCINNATI CHILDRENS HOSP MED CTR · PI Bruce J Aronow, Nathan G. Salomonis · 2019 to 2026
$12.4MSystems Pharmacology of Therapeutic and Adverse Responses to ImmuneCheckpoint and Small Molecule DrugsU54CA225088 · NCI · HARVARD MEDICAL SCHOOL · PI SORGER, PETER KARL · 2018 to 2022
$10.8MPersonal tumor neoantigens for immunity against chronic lymphocytic leukemiaR01CA155010 · NCI · DANA-FARBER CANCER INST · PI Catherine Ju-Ying Wu · 2011 to 2026
$9.6MLungMap Phase II - Building a multidimensional map of developing human lungU01HL148856 · NHLBI · CINCINNATI CHILDRENS HOSP MED CTR · PI WHITSETT, JEFFREY A, XU, YAN · 2019 to 2023
$4.5MThe roles of anti-apoptotic proteins BCL-XL and MCL1 in mediating survival of high-grade serous ovarian cancer following drug-induced DNA damageK08CA237871 · NCI · DANA-FARBER CANCER INST · PI STOVER, ELIZABETH HARMON · 2019 to 2023
$921kDissecting mechanisms of immunotherapy resistance in melanoma patientsK08CA222663 · NCI · DANA-FARBER CANCER INST · PI IZAR, BENJAMIN · 2017 to 2021
$827kNCI NIH HHS HHSN261201500003CNCI NIH HHS HHSN261201500003INCI NIH HHS K08 CA222663NCI NIH HHS K08 CA237871NCI NIH HHS R01 CA155010NCI NIH HHS U2C CA233195NCI NIH HHS U54 CA225088NHLBI NIH HHS U01 HL148856NHLBI NIH HHS U24 HL148865NIDDK NIH HHS P30 DK043351NIDDK NIH HHS RC2 DK116691
Abstract
Single-cell genomics is essential to chart tumor ecosystems. Although single-cell RNA-Seq (scRNA-Seq) profiles RNA from cells dissociated from fresh tumors, single-nucleus RNA-Seq (snRNA-Seq) is needed to profile frozen or hard-to-dissociate tumors. Each requires customization to different tissue and tumor types, posing a barrier to adoption. Here, we have developed a systematic toolbox for profiling fresh and frozen clinical tumor samples using scRNA-Seq and snRNA-Seq, respectively. We analyzed 216,490 cells and nuclei from 40 samples across 23 specimens spanning eight tumor types of varying tissue and sample characteristics. We evaluated protocols by cell and nucleus quality, recovery rate and cellular composition. scRNA-Seq and snRNA-Seq from matched samples recovered the same cell types, but at different proportions. Our work provides guidance for studies in a broad range of tumors, including criteria for testing and selecting methods from the toolbox for other tumors, thus paving the way for charting tumor atlases.
Indexed as
AlgorithmsAdultAnimalsCell NucleusChildComputational BiologyExome SequencingFemaleFreezingGene Expression ProfilingGene Expression Regulation, NeoplasticGenomicsHumansMiceMice, KnockoutMice, Nude
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