Evidence map›Paper›PMID 38260392›Full record

ArticlebioRxiv : the preprint server for biology2024

A spatial cell atlas of neuroblastoma reveals developmental, epigenetic and spatial axis of tumor heterogeneity.

Anand G Patel, Orr Ashenberg, Natalie B Collins, Åsa Segerstolpe, Sizun Jiang, Michal Slyper, Xin Huang, Chiara Caraccio, Hongjian Jin, Heather Sheppard and 47 more

Open access · greenAbstract readPreprint
In one paragraph

Article in bioRxiv : the preprint server for biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed, 28 citations in OpenAlex.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

57 authors at 8 institutions in 1 country.

Anand G PatelDepartment of Oncology, St. Jude Children's Research Hospital, Memphis, TN, USA.
Orr AshenbergKlarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID 0000-0002-7802-8834
Natalie B CollinsDana-Farber/Boston Children's Cancer and Blood Disorders Center, Harvard Medical School, Boston, MA, USA.ORCID 0000-0003-2980-9244
Åsa SegerstolpeKlarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID 0000-0002-3700-9661
Sizun JiangDepartment of Pathology, Stanford University, Stanford, CA, USA.ORCID 0000-0001-6149-3142
Michal SlyperKlarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID 0000-0002-3002-0366
Xin HuangDepartment of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN, USA.
Chiara CaraccioDepartment of Pathology, Stanford University, Stanford, CA, USA.
Hongjian JinCenter for Applied Bioinformatics, St. Jude Children's Research Hospital, Memphis, TN, USA.
Heather SheppardComparative Pathology Core, St. Jude Children's Research Hospital, Memphis, TN, USA.ORCID 0000-0002-9623-2812
Ke XuCenter for Applied Bioinformatics, St. Jude Children's Research Hospital, Memphis, TN, USA.ORCID 0000-0002-8130-1109
Ti-Cheng ChangCenter for Applied Bioinformatics, St. Jude Children's Research Hospital, Memphis, TN, USA.
Brent A OrrDepartment of Pathology, St. Jude Children's Research Hospital, Memphis, TN, USA.ORCID 0000-0003-0997-4728
Abbas ShirinifardDepartment of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN, USA.
Richard H ChappleDepartment of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN, USA.ORCID 0000-0002-0375-2043
Amber ShenBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Michael R ClayDepartment of Pathology, University of Colorado School of Medicine, Aurora, CO, USA.ORCID 0000-0003-1659-8927
Ruth G TatevossianCancer Biomarkers Laboratory, St. Jude Children's Research Hospital, Memphis, TN, USA.ORCID 0000-0002-1653-3026
Colleen ReillyDepartment of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN, USA.ORCID 0000-0003-3119-9940
Jaimin PatelDepartment of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN, USA.ORCID 0000-0001-6754-6030
Marybeth LupoDepartment of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN, USA.
Cynthia ClineDepartment of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN, USA.
Danielle DionneKlarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Caroline B M PorterKlarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Julia WaldmanKlarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID 0000-0002-0584-5833
Yunhao BaiDepartment of Pathology, Stanford University, Stanford, CA, USA.
Bokai ZhuDepartment of Pathology, Stanford University, Stanford, CA, USA.ORCID 0000-0003-3599-9419
Irving BarreraBroad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID 0000-0001-6099-4316
Evan MurrayBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Sébastien VigneauCenter for Cancer Genomics, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.ORCID 0000-0002-9091-2067
Sara NapolitanoCenter for Cancer Genomics, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Isaac WakiroCenter for Cancer Genomics, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Jingyi WuCenter for Cancer Genomics, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Grace GrimaldiCenter for Cancer Genomics, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Laura DellostrittoCenter for Cancer Genomics, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Karla HelvieCenter for Cancer Genomics, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Asaf RotemCenter for Cancer Genomics, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Ana LakoCenter for Immuno-Oncology (CIO), Dana-Farber Cancer Institute, Boston, MA, USA.
Nicole CullenCenter for Immuno-Oncology (CIO), Dana-Farber Cancer Institute, Boston, MA, USA.
Kathleen L PfaffCenter for Immuno-Oncology (CIO), Dana-Farber Cancer Institute, Boston, MA, USA.ORCID 0000-0003-3311-5384
Åsa KarlströmDepartment of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN, USA.
Judit Jané-ValbuenaKlarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID 0000-0002-5651-1745
Ellen TodresKlarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID 0000-0001-9289-4432
Aaron ThornerCenter for Cancer Genomics, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Paul GeeleherDepartment of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN, USA.ORCID 0000-0002-5128-0087
Scott J RodigDepartment of Pathology, Brigham and Women's Hospital, Boston, MA, USA.
Xin ZhouDepartment of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN, USA.
Elizabeth StewartDepartment of Oncology, St. Jude Children's Research Hospital, Memphis, TN, USA.
Bruce E JohnsonCenter for Cancer Genomics, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Gang WuCenter for Applied Bioinformatics, St. Jude Children's Research Hospital, Memphis, TN, USA.ORCID 0000-0002-1678-5864
Fei ChenBroad Institute of MIT and Harvard, Boston, MA, USA.ORCID 0000-0003-2308-3649
Jiyang YuDepartment of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN, USA.ORCID 0000-0003-1244-4429
Yury GoltsevDepartment of Pathology, Stanford University, Stanford, CA, USA.
Garry P NolanDepartment of Pathology, Stanford University, Stanford, CA, USA.ORCID 0000-0002-8862-9043
Orit Rozenblatt-RosenKlarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Aviv RegevKlarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID 0000-0003-3293-3158
Michael A DyerDepartment of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN, USA.
St. Jude Children's Research Hospital · USBroad Institute · USDana-Farber Cancer Institute · USStanford University · USBeth Israel Deaconess Medical Center · USBrigham and Women's Hospital · USHarvard University · USUniversity of Colorado Denver · US

Funding

Viral Vector Technology (VVTSR)P30CA021765 · NCI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI Shondra Michelle Miller · 1985 to 2026
$166.9M
Cancer Immune Monitoring and Analysis CenterU24CA224331 · NCI · DANA-FARBER CANCER INST · PI FRANK S HODI, Catherine Ju-Ying Wu · 2017 to 2026
$18.4M
The Cellular Geography of Therapeutic Resistance in CancerU2CCA233195 · NCI · DANA-FARBER CANCER INST · PI VAN ALLEN, ELIEZER M · 2018 to 2023
$13.7M
Novel Therapeutic Approaches for the Treatment of NeuroblastomaR01CA248432 · NCI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI DYER, MICHAEL A · 2020 to 2024
$2.4M
Novel Therapeutic Approaches for the Treatment of RhabdomyosarcomaR01CA219686 · NCI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI DYER, MICHAEL A · 2017 to 2021
$2.0M
Cell-type– and developmental stage–specific regulation of gene expression in the retinaR01EY030180 · NEI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI DYER, MICHAEL A · 2020 to 2023
$1.8M
NCI NIH HHS HHSN261201500003CNCI NIH HHS HHSN261201500003INCI NIH HHS P30 CA021765NCI NIH HHS R01 CA219686NCI NIH HHS R01 CA248432NCI NIH HHS U24 CA224331NCI NIH HHS U2C CA233195NEI NIH HHS R01 EY030180
6 · The paper itself

Abstract

Neuroblastoma is a pediatric cancer arising from the developing sympathoadrenal lineage with complex inter- and intra-tumoral heterogeneity. To chart this complexity, we generated a comprehensive cell atlas of 55 neuroblastoma patient tumors, collected from two pediatric cancer institutions, spanning a range of clinical, genetic, and histologic features. Our atlas combines single-cell/nucleus RNA-seq (sc/scRNA-seq), bulk RNA-seq, whole exome sequencing, DNA methylation profiling, spatial transcriptomics, and two spatial proteomic methods. Sc/snRNA-seq revealed three malignant cell states with features of sympathoadrenal lineage development. All of the neuroblastomas had malignant cells that resembled sympathoblasts and the more differentiated adrenergic cells. A subset of tumors had malignant cells in a mesenchymal cell state with molecular features of Schwann cell precursors. DNA methylation profiles defined four groupings of patients, which differ in the degree of malignant cell heterogeneity and clinical outcomes. Using spatial proteomics, we found that neuroblastomas are spatially compartmentalized, with malignant tumor cells sequestered away from immune cells. Finally, we identify spatially restricted signaling patterns in immune cells from spatial transcriptomics. To facilitate the visualization and analysis of our atlas as a resource for further research in neuroblastoma, single cell, and spatial-omics, all data are shared through the Human Tumor Atlas Network Data Commons at www.humantumoratlas.org.

Indexed as

immunotherapyintratumoral heterogeneityNeuroblastomasingle-cell biology

Identifiers

PMID38260392
PMCPMC10802404
OpenAlexW4390660975

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.