Evidence map›Paper›PMID 40229600›Full record

ArticleNature genetics2025

Longitudinal single-cell multiomic atlas of high-risk neuroblastoma reveals chemotherapy-induced tumor microenvironment rewiring.

Wenbao Yu, Rumeysa Biyik-Sit, Yasin Uzun, Chia-Hui Chen, Anusha Thadi, Jonathan H Sussman, Minxing Pang, Chi-Yun Wu, Liron D Grossmann, Peng Gao and 16 more

Abstract read
In one paragraph

Article in Nature genetics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.

0numbers the graph read from it
0cells of the map it votes in
36citing 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

36 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
  4. Integration of Bulk RNA Sequencing and Single-Cell Sequencing to Identify Prognostic Genes Associated With MCDRGs in Neuroblastoma.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026
    Article
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  8. Review
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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

26 authors.

Wenbao Yu *Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0001-8860-2644
Rumeysa Biyik-Sit *Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Yasin Uzun *Department of Pediatrics, Pennsylvania State University College of Medicine, Hershey, PA, USA.
Chia-Hui Chen *Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0001-5239-1574
Anusha ThadiCenter for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0002-1271-0398
Jonathan H SussmanMedical Scientist Training Program, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0002-3057-3550
Minxing PangApplied Mathematics and Computational Science Graduate Group, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0001-5208-5972
Chi-Yun WuGraduate Group in Genomics and Computational Biology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Liron D GrossmannCenter for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Peng GaoDepartment of Hematology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
David W WuMedical Scientist Training Program, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0001-6197-7091
Aliza YouseyCenter for Single Cell Biology, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Mei ZhangCenter for Single Cell Biology, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Christina S TurnCenter for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Zhan ZhangDepartment of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA.
Shovik BandyopadhyayMedical Scientist Training Program, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Jeffrey HuangDepartment of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA.
Tasleema PatelCenter for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Changya ChenCenter for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Daniel MartinezDepartment of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Lea F SurreyDepartment of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0002-6944-2232
Michael D HogartyCenter for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0002-9221-4852
Kathrin BerntCenter for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0002-0691-356X
Nancy R ZhangDepartment of Statistics and Data Science, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0002-0880-5749
John M MarisCenter for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0002-8088-7929
Kai TanCenter for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, PA, USA. tank1@chop.edu.ORCID http://orcid.org/0000-0002-9104-5567

Funding

HEMATOLOGY CLINICAL RESEARCH TRAINING PROGRAMT32HL007439 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI LAWRENCE F BRASS, PETER S KLEIN · 1985 to 2026
$17.1M
IMMUNOBIOLOGY OF NORMAL AND NEOPLASTIC LYMPHOCYTEST32CA009140 · NCI · UNIVERSITY OF PENNSYLVANIA · PI Malay Haldar, WARREN S PEAR · 1985 to 2026
$16.1M
Data Analysis UnitU2CCA233285 · NCI · CHILDREN'S HOSP OF PHILADELPHIA · PI TAN, KAI · 2018 to 2023
$13.2M
Organ Specific Project - HeartU54HL165442 · NHLBI · CHILDREN'S HOSP OF PHILADELPHIA · PI MOFFITT, JEFFREY, PEI, LIMING · 2022 to 2025
$7.6M
American Cancer Society (American Cancer Society, Inc.) IRG-22-150-41-IRGNCI NIH HHS T32 CA009140NCI NIH HHS U2C CA233285NHLBI NIH HHS T32 HL007439NHLBI NIH HHS U54 HL165442
6 · The paper itself

Abstract

High-risk neuroblastoma, a leading cause of pediatric cancer mortality, exhibits substantial intratumoral heterogeneity, contributing to therapeutic resistance. To understand tumor microenvironment evolution during therapy, we longitudinally profiled 22 patients with high-risk neuroblastoma before and after induction chemotherapy using single-nucleus RNA and ATAC sequencing and whole-genome sequencing. This revealed profound shifts in tumor and immune cell subpopulations after therapy and identified enhancer-driven transcriptional regulators of neuroblastoma neoplastic states. Poor outcome correlated with proliferative and metabolically active neoplastic states, whereas more differentiated neuronal-like states predicted better prognosis. Proportions of mesenchymal neoplastic cells increased after therapy and a high proportion correlated with a poorer chemotherapy response. Macrophages significantly expanded towards pro-angiogenic, immunosuppressive and metabolic phenotypes. We identified paracrine signaling networks and validated the HB-EGF-ERBB4 axis between macrophage and neoplastic subsets, which promoted tumor growth through the induction of ERK signaling. These findings collectively reveal intrinsic and extrinsic regulators of therapy response in high-risk neuroblastoma.

Indexed as

NeuroblastomaTumor MicroenvironmentChild, PreschoolFemaleGene Expression Regulation, NeoplasticHumansLongitudinal StudiesMacrophagesMalePrognosisSingle-Cell Analysis

Identifiers

PMID40229600
PMCPMC12081299

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Registered trials

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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.