Evidence map›Paper›PMID 40021625›Full record

ArticleNature communications2025

Bone morphogenetic protein (BMP) signaling determines neuroblastoma cell fate and sensitivity to retinoic acid.

Min Pan, Yinwen Zhang, William C Wright, Xueying Liu, Barbara Passaia, Duane Currier, Jonathan Low, Richard H Chapple, Jacob A Steele, Jon P Connelly and 16 more

Abstract read
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

26 authors.

Min Pan *Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN, 38105, USA. min.pan@stjude.org.ORCID http://orcid.org/0000-0002-9338-8491
Yinwen Zhang *Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN, 38105, USA.
William C WrightDepartment of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN, 38105, USA.ORCID http://orcid.org/0000-0002-2274-9966
Xueying LiuDepartment of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN, 38105, USA.ORCID http://orcid.org/0000-0003-0654-2591
Barbara PassaiaDepartment of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN, 38105, USA.ORCID http://orcid.org/0000-0001-8933-2586
Duane CurrierDepartment of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis, TN, 38105, USA.ORCID http://orcid.org/0000-0002-0123-0233
Jonathan LowDepartment of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis, TN, 38105, USA.
Richard H ChappleDepartment of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN, 38105, USA.ORCID http://orcid.org/0000-0002-0375-2043
Jacob A SteeleDepartment of Cell and Molecular Biology, St. Jude Children's Research Hospital, Memphis, TN, 38105, USA.ORCID http://orcid.org/0000-0001-9924-2226
Jon P ConnellyDepartment of Cell and Molecular Biology, St. Jude Children's Research Hospital, Memphis, TN, 38105, USA.ORCID http://orcid.org/0000-0002-5564-1775
Bensheng JuDepartment of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN, 38105, USA.
Emily PlylerDepartment of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN, 38105, USA.
Meifen LuDepartment of Pathology, St. Jude Children's Research Hospital, Memphis, TN, 38105, USA.
Allister J LoughranDepartment of Cell and Molecular Biology, St. Jude Children's Research Hospital, Memphis, TN, 38105, USA.ORCID http://orcid.org/0000-0002-6564-5526
Lei YangDepartment of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis, TN, 38105, USA.ORCID http://orcid.org/0000-0002-3060-0790
Brian J AbrahamDepartment of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN, 38105, USA.ORCID http://orcid.org/0000-0001-8085-3027
Shondra M Pruett-MillerDepartment of Cell and Molecular Biology, St. Jude Children's Research Hospital, Memphis, TN, 38105, USA.ORCID http://orcid.org/0000-0002-3793-585X
Burgess FreemanPreclinical Pharmacokinetic Shared Resource, St. Jude Children's Research Hospital, Memphis, TN, 38105, USA.ORCID http://orcid.org/0000-0003-2174-5119
George E CampbellCellular Imaging Shared Resource, St. Jude Children's Research Hospital, Memphis, TN, 38105, USA.ORCID http://orcid.org/0000-0003-1288-2576
Michael A DyerDepartment of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN, 38105, USA.ORCID http://orcid.org/0000-0003-4027-4850
Taosheng ChenDepartment of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis, TN, 38105, USA.ORCID http://orcid.org/0000-0001-6420-3809
Elizabeth StewartCellular Imaging Shared Resource, St. Jude Children's Research Hospital, Memphis, TN, 38105, USA.ORCID http://orcid.org/0000-0001-8005-0427
Selene KooDepartment of Pathology, St. Jude Children's Research Hospital, Memphis, TN, 38105, USA.ORCID http://orcid.org/0000-0001-8459-2469
Heather SheppardDepartment of Pathology, St. Jude Children's Research Hospital, Memphis, TN, 38105, USA.ORCID http://orcid.org/0000-0002-9623-2812
John EastonDepartment of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN, 38105, USA. john.easton@stjude.org.ORCID http://orcid.org/0000-0003-4503-6608
Paul GeeleherDepartment of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN, 38105, USA. paul.geeleher@stjude.org.ORCID http://orcid.org/0000-0002-5128-0087

Funding

Viral Vector Technology (VVTSR)P30CA021765 · NCI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI Shondra Michelle Miller · 1985 to 2026
$166.9M
Developing new therapeutic strategies for pediatric tumors that lack clinically actionable mutationsR01CA260060 · NCI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI Paul Geeleher · 2021 to 2026
$3.0M
Computational tools for estimating cell-type-specific effects in bulk RNA-seq and spatial transcriptomics data, using reference single-cell RNA-seq datasetsR35GM138293 · NIGMS · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI GEELEHER, PAUL · 2020 to 2024
$2.2M
Novel computational approaches for pharmacogenomic discoveryR00HG009679 · NHGRI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI GEELEHER, PAUL · 2019 to 2021
$739k
NCI NIH HHS P30 CA021765NCI NIH HHS R01 CA260060NHGRI NIH HHS R00 HG009679NIGMS NIH HHS R35 GM138293U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS) R35GM138293
6 · The paper itself

Abstract

Retinoic acid (RA) is a standard-of-care neuroblastoma drug thought to be effective by inducing differentiation. Curiously, RA has little effect on primary human tumors during upfront treatment but can eliminate neuroblastoma cells from the bone marrow during post-chemo maintenance therapy-a discrepancy that has never been explained. To investigate this, we treat a large cohort of neuroblastoma cell lines with RA and observe that the most RA-sensitive cells predominantly undergo apoptosis or senescence, rather than differentiation. We conduct genome-wide CRISPR knockout screens under RA treatment, which identify bone morphogenic protein (BMP) signaling as controlling the apoptosis/senescence vs differentiation cell fate decision and determining RA's overall potency. We then discover that BMP signaling activity is markedly higher in neuroblastoma patient samples at bone marrow metastatic sites, providing a plausible explanation for RA's ability to clear neuroblastoma cells specifically from the bone marrow, by seemingly mimicking interactions between BMP and RA during normal development.

Indexed as

Antineoplastic AgentsBone Morphogenetic ProteinsNeuroblastomaSignal TransductionTretinoinApoptosisCell DifferentiationCell Line, TumorHumansAntineoplastic AgentsBone Morphogenetic ProteinsTretinoin

Identifiers

PMID40021625
PMCPMC11871043

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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.