Evidence map›Paper›PMID 41448181›Full record

ArticleCell stem cell2026

Rebalancing NTRK2 isoforms promotes vascular regeneration in bronchopulmonary dysplasia.

Yunpei Zhang, Cheng Tan, Ziyi Liu, Xiangdi Mao, Cheng Jiang, Afzaal Nadeem Mohammed, Xiaolei Li, Renzhong Lu, Anmin Wang, Wusiman Maihemuti and 13 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell stem cell, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Article
  2. Angiogenesis in Lung Regeneration and Aging.Arteriosclerosis, thrombosis, and vascular biology · 2026
    Review
  3. Article
  4. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

23 authors.

Yunpei ZhangDepartment of Anesthesiology and Perioperative Medicine, David Geffen School of Medicine, Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Biology, University of California, Los Angeles (UCLA), Los Angeles, CA 90095, USA.
Cheng TanPerinatal Institute, Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA; Center for Stem Cell and Organoid Medicine (CuSTOM), Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
Ziyi LiuPerinatal Institute, Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA; Center for Stem Cell and Organoid Medicine (CuSTOM), Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
Xiangdi MaoDepartment of Anesthesiology and Perioperative Medicine, David Geffen School of Medicine, Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Biology, University of California, Los Angeles (UCLA), Los Angeles, CA 90095, USA.
Cheng JiangPerinatal Institute, Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Afzaal Nadeem MohammedPhoenix Children's Research Institute, Department of Child Health, University of Arizona College of Medicine-Phoenix, Phoenix, AZ, USA; Division of Neonatology, Phoenix Children's Hospital, Phoenix, AZ, USA.
Xiaolei LiPerinatal Institute, Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA; Center for Stem Cell and Organoid Medicine (CuSTOM), Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
Renzhong LuDepartment of Cardiovascular Sciences, Houston Methodist Research Institute, Houston, TX, USA.
Anmin WangDepartment of Anesthesiology and Perioperative Medicine, David Geffen School of Medicine, Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Biology, University of California, Los Angeles (UCLA), Los Angeles, CA 90095, USA.
Wusiman MaihemutiDepartment of Anesthesiology and Perioperative Medicine, David Geffen School of Medicine, Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Biology, University of California, Los Angeles (UCLA), Los Angeles, CA 90095, USA.
Nicole PekPerinatal Institute, Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA; Center for Stem Cell and Organoid Medicine (CuSTOM), Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
Hailu FuDepartment of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA; Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL, USA.
Omar MilbesDepartment of Anesthesiology and Perioperative Medicine, David Geffen School of Medicine, Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Biology, University of California, Los Angeles (UCLA), Los Angeles, CA 90095, USA.
Kavya PandrangiDepartment of Anesthesiology and Perioperative Medicine, David Geffen School of Medicine, Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Biology, University of California, Los Angeles (UCLA), Los Angeles, CA 90095, USA.
Colin Patrick JohnsonDepartment of Anesthesiology and Perioperative Medicine, David Geffen School of Medicine, Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Biology, University of California, Los Angeles (UCLA), Los Angeles, CA 90095, USA.
Varun SekarDepartment of Anesthesiology and Perioperative Medicine, David Geffen School of Medicine, Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Biology, University of California, Los Angeles (UCLA), Los Angeles, CA 90095, USA.
Yaping LiuDepartment of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA; Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL, USA.
Li LaiDepartment of Cardiovascular Sciences, Houston Methodist Research Institute, Houston, TX, USA.
Gloria S PryhuberDivision of Neonatology, Department of Pediatrics, University of Rochester Medical Center, Rochester, NY, USA.
Vladimir V KalinichenkoDepartment of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA; Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL, USA.
Yifei MiaoPerinatal Institute, Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA; Center for Stem Cell and Organoid Medicine (CuSTOM), Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA. Electronic address: yifei.miao@ioz.ac.cn.
Minzhe GuoPerinatal Institute, Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA. Electronic address: minzhe.guo@cchmc.org.
Mingxia GuDepartment of Anesthesiology and Perioperative Medicine, David Geffen School of Medicine, Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Biology, University of California, Los Angeles (UCLA), Los Angeles, CA 90095, USA; Perinatal Institute, Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA; Center for Stem Cell and Organoid Medicine (CuSTOM), Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA. Electronic address: mgu@mednet.ucla.edu.

Funding

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
Biorepository for Investigation of Neonatal Diseases of Lung-Normal (BRINDL-NL)U01HL122700 · NHLBI · UNIVERSITY OF ROCHESTER · PI PRYHUBER, GLORIA S · 2014 to 2018
$6.1M
LungMap 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
$4.5M
Development of novel therapeutic approaches for treatment of Alveolar Capillary DysplasiaR01HL152973 · NHLBI · UNIVERSITY OF ARIZONA · PI Vladimir Kalinichenko · 2021 to 2026
$3.6M
Elucidating the FOXF1 gene regulatory network in human alveologenesisR01HL166283 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Mingxia Gu · 2023 to 2026
$1.9M
Metabolism and Epigenetic Regulation are Couples in Transdifferentiation and Vascular RegenerationR56HL169204 · NHLBI · METHODIST HOSPITAL RESEARCH INSTITUTE · PI LAI, LI · 2023 to 2023
$404k
NHLBI NIH HHS R01 HL152973NHLBI NIH HHS R01 HL166283NHLBI NIH HHS R56 HL169204NHLBI NIH HHS U01 HL122700NHLBI NIH HHS U01 HL148856NHLBI NIH HHS U24 HL148865
6 · The paper itself

Abstract

Bronchopulmonary dysplasia (BPD) is a chronic lung disease of prematurity with no curative therapy, characterized by impaired alveologenesis and capillary formation. However, the molecular mechanisms underlying endothelial dysfunction, a key driver of BPD pathogenesis, remain poorly understood. Through multiomic profiling of endothelial cells isolated from human BPD lungs, we identified an expansion of general capillary endothelial cells (gCaps) marked by neurotrophic receptor tyrosine kinase 2 (NTRK2). Notably, we uncovered a critical isoform switch that governs gCap regeneration. Full-length NTRK2 (NTRK2-FL) promoted gCap repair after hyperoxic injury, whereas RBFOX2-mediated splicing of NTRK2-FL into a truncated isoform (NTRK2-T1) contributed to maladaptive responses and persistent alveolar simplification. Restoring NTRK2-FL using lipid nanoparticle-delivered mRNA promoted angiogenesis in vessel organoids and reversed alveolar simplification in hyperoxic mice. These findings identified NTRK2 isoform imbalance as a key driver of endothelial dysfunction and support isoform-specific RNA therapy as a promising strategy for vascular regeneration and repair.

Indexed as

Bronchopulmonary DysplasiaNeovascularization, PhysiologicReceptor, trkBRegenerationAnimalsEndothelial CellsHumansLungMembrane GlycoproteinsMiceMice, Inbred C57BLProtein IsoformsMembrane GlycoproteinsProtein IsoformsReceptor, trkBtropomyosin-related kinase-B, humanbronchopulmonary dysplasiaiPSC-derived vessel organoidslipid nanoparticlesmultiomeNTRK2 isoformRBFOX2RNA therapyvascular regeneration

Identifiers

PMID41448181
PMCPMC13004638

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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.