Evidence map›Paper›PMID 42241577›Full record

ArticleJCI insight2026

Neural crest cell signatures drive tumorigenesis in tuberous sclerosis complex and lymphangioleiomyomatosis.

Uchenna J Unachukwu, Enio B Garcia, Nooralam Rai, Jeanine M D'Armiento

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in JCI insight, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

4 authors.

Uchenna J UnachukwuCenter for LAM and Rare Lung Disease, Department of Anesthesiology, College of Physicians and Surgeons, Columbia University Medical Center, New York, New York, USA.
Enio B GarciaCenter for LAM and Rare Lung Disease, Department of Anesthesiology, College of Physicians and Surgeons, Columbia University Medical Center, New York, New York, USA.
Nooralam RaiDepartment of Pediatrics (Pulmonary), Columbia University Medical Center, New York, New York, USA.
Jeanine M D'ArmientoCenter for LAM and Rare Lung Disease, Department of Anesthesiology, College of Physicians and Surgeons, Columbia University Medical Center, New York, New York, USA.

Funding

Tumor Biology and Microenvironment ProgramP30CA013696 · NCI · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI Anil K Rustgi · 1985 to 2026
$115.3M
The 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
$12.4M
Molecular Biomarkers in pathogenesis of Lymphangioleiomyomatosis (LAM)R01HL167137 · NHLBI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI Jeanine M D'Armiento · 2023 to 2026
$2.6M
NCI NIH HHS P30 CA013696NHLBI NIH HHS R01 HL167137NHLBI NIH HHS U24 HL148865
6 · The paper itself

Abstract

Tuberous sclerosis complex (TSC) and lymphangioleiomyomatosis (LAM) lack well-defined cellular origins, limiting treatment options. In this report, scRNA-seq of Tsc2+/- mouse renal cystadenomas revealed an 80-fold increase in a tumor cell subpopulation with neural crest features, expressing known cranial neural crest genes as SRY box transcription factor 9 (Sox9), transcription factor activator protein (Tfap2a), and candidate neurocristopathy markers, osteopontin (Spp1), lipocalin-2 (Lcn2), clusterin (Clu), and cytokeratin 18 (Krt18). These signatures were validated in mouse tumors and LAM patient lesions and serum, identifying a tumor phenotype distinct from traditional VEGFD detection. Pathway analysis indicated activation of WNT/SHH signaling, nephric duct formation, and protumorigenic signals, with transcription factor 7 (Tcf7) and ephrin-A ligands as key upstream regulators. Spp1 KO in cranial neural crest cells (CNCCs) significantly reduced proliferation (28%-33%), migration (54%-76%), and invasion (29%-64%) without affecting viability, while Tsc2 KO increased viability 3- to 6-fold with minimal effect on chemotaxis. Elevated serum levels of SPP1 and KRT18 in 1 subset of patients with LAM, decreased LCN2 in nearly all cases, and distinct increases in VEGFD in a separate subset suggest complementary roles for these biomarkers. Overall, findings support a neurocristopathic model of tumor development in TSC and LAM and identify potential biomarkers and therapeutic targets beyond mTOR inhibition.

Indexed as

CarcinogenesisLymphangioleiomyomatosisNeural CrestTuberous SclerosisAnimalsFemaleHumansMiceMice, KnockoutOsteopontinTuberous Sclerosis Complex 2 ProteinOsteopontinSpp1 protein, mouseTsc2 protein, mouseTuberous Sclerosis Complex 2 ProteinBiomarkersCancerCell biologyClinical ResearchOncologyStem Cells

Identifiers

PMID42241577
PMCPMC13461175

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.