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Genome-wide functional genomics screens identify therapeutic vulnerabilities for lymphangioleiomyomatosis

https://doi.org/10.1101/683359
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What this work says

Outgoing claims: the papers this work cites, builds on, or argues with.

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Markers of cellular proliferation are expressed in cortical tubers
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Altered inhibition in tuberous sclerosis and type IIb cortical dysplasia
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LOVD v.2.0: the next generation in gene variant databases
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Clinical Predictors of Mortality and Cause of Death in Lymphangioleiomyomatosis: A Population-based Registry
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Formation and migration of neural crest cells in the vertebrate embryo
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In pulmonary lymphangioleiomyomatosis expression of progesterone receptor is frequently higher than that of estrogen receptor
inferredcites →https://doi.org/10.1016/j.ajpath.2013.04.002openalex-snapshot
Positioning Ganglioside D3 as an Immunotherapeutic Target in Lymphangioleiomyomatosis
inferredcites →https://doi.org/10.1016/j.cell.2017.02.004openalex-snapshot
mTOR Signaling in Growth, Metabolism, and Disease
inferredcites →https://doi.org/10.1016/j.celrep.2016.02.090openalex-snapshot
mTORC1 Inhibition Corrects Neurodevelopmental and Synaptic Alterations in a Human Stem Cell Model of Tuberous Sclerosis
inferredcites →https://doi.org/10.1016/j.celrep.2016.09.054openalex-snapshot
Impaired Mitochondrial Dynamics and Mitophagy in Neuronal Models of Tuberous Sclerosis Complex
inferredcites →https://doi.org/10.1016/j.celrep.2018.04.108openalex-snapshot
Early Seizures Prematurely Unsilence Auditory Synapses to Disrupt Thalamocortical Critical Period Plasticity
inferredcites →https://doi.org/10.1016/j.neuron.2013.03.017openalex-snapshot
Excitatory/Inhibitory Synaptic Imbalance Leads to Hippocampal Hyperexcitability in Mouse Models of Tuberous Sclerosis
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Feeder-independent derivation of induced-pluripotent stem cells from peripheral blood endothelial progenitor cells
inferredcites →https://doi.org/10.1016/j.stem.2010.07.017openalex-snapshot
Identification and Classification of Chromosomal Aberrations in Human Induced Pluripotent Stem Cells
inferredcites →https://doi.org/10.1016/j.stem.2017.08.015openalex-snapshot
A Modular Platform for Differentiation of Human PSCs into All Major Ectodermal Lineages
inferredcites →https://doi.org/10.1016/j.stem.2018.11.021openalex-snapshot
Lysosomal Signaling Licenses Embryonic Stem Cell Differentiation via Inactivation of Tfe3
inferredcites →https://doi.org/10.1016/j.yebeh.2018.09.020openalex-snapshot
The use of rapamycin in patients with tuberous sclerosis complex: Long-term results
inferredcites →https://doi.org/10.1016/s0002-9440(10)64237-xopenalex-snapshot
Functional Tyrosine Kinase Inhibitor Profiling
inferredcites →https://doi.org/10.1038/mp.2017.56openalex-snapshot
A simplified protocol for differentiation of electrophysiologically mature neuronal networks from human induced pluripotent stem cells
inferredcites →https://doi.org/10.1038/nature13492openalex-snapshot
Coordinated regulation of protein synthesis and degradation by mTORC1
inferredcites →https://doi.org/10.1038/nbt.1529openalex-snapshot
Highly efficient neural conversion of human ES and iPS cells by dual inhibition of SMAD signaling
inferredcites →https://doi.org/10.1038/nbt.2647openalex-snapshot
DNA targeting specificity of RNA-guided Cas9 nucleases
inferredcites →https://doi.org/10.1038/ncomms15816openalex-snapshot
The genomic landscape of tuberous sclerosis complex
inferredcites →https://doi.org/10.1038/nmeth.1593openalex-snapshot
Chemically defined conditions for human iPSC derivation and culture
inferredcites →https://doi.org/10.1038/nmeth.2019openalex-snapshot
Fiji: an open-source platform for biological-image analysis
inferredcites →https://doi.org/10.1038/nmeth.4197openalex-snapshot
Salmon provides fast and bias-aware quantification of transcript expression
inferredcites →https://doi.org/10.1038/nprot.2013.055openalex-snapshot
Imaging of neutral lipids by oil red O for analyzing the metabolic status in health and disease
inferredcites →https://doi.org/10.1038/nprot.2013.143openalex-snapshot
Genome engineering using the CRISPR-Cas9 system
inferredcites →https://doi.org/10.1038/s41388-018-0381-2openalex-snapshot
Loss of tuberous sclerosis complex 2 sensitizes tumors to nelfinavir−bortezomib therapy to intensify endoplasmic reticulum stress-induced cell death
inferredcites →https://doi.org/10.1038/s41388-018-0625-1openalex-snapshot
Mitochondrial dysfunction is a key determinant of the rare disease lymphangioleiomyomatosis and provides a novel therapeutic target
inferredcites →https://doi.org/10.1038/s41540-017-0037-9openalex-snapshot
VEGFR1 promotes cell migration and proliferation through PLCγ and PI3K pathways
inferredcites →https://doi.org/10.1038/s41591-018-0139-yopenalex-snapshot
Genetically engineered human cortical spheroid models of tuberous sclerosis
inferredcites →https://doi.org/10.1056/nejmoa1100391openalex-snapshot
Efficacy and Safety of Sirolimus in Lymphangioleiomyomatosis
inferredcites →https://doi.org/10.1073/pnas.0407971101openalex-snapshot
Molecular and genetic analysis of disseminated neoplastic cells in lymphangioleiomyomatosis
inferredcites →https://doi.org/10.1073/pnas.0903621106openalex-snapshot
Rheb controls misfolded protein metabolism by inhibiting aggresome formation and autophagy
inferredcites →https://doi.org/10.1073/pnas.1104361108openalex-snapshot
Tumorigenesis in tuberous sclerosis complex is autophagy and p62/sequestosome 1 (SQSTM1)-dependent
inferredcites →https://doi.org/10.1073/pnas.1106454108openalex-snapshot
Regulable neural progenitor-specific Tsc1 loss yields giant cells with organellar dysfunction in a model of tuberous sclerosis complex
inferredcites →https://doi.org/10.1073/pnas.151033798openalex-snapshot
A germ-line Tsc1 mutation causes tumor development and embryonic lethality that are similar, but not identical to, those caused by Tsc2 mutation in mice
inferredcites →https://doi.org/10.1073/pnas.93.24.14152openalex-snapshot
Embryonic neuronal markers in tuberous sclerosis: Single-cell molecular pathology
inferredcites →https://doi.org/10.1074/jbc.aac118.004855openalex-snapshot
Quantifying intracellular rates of glycolytic and oxidative ATP production and consumption using extracellular flux measurements
inferredcites →https://doi.org/10.1074/jbc.m112.431056openalex-snapshot
Mammalian Target of Rapamycin Complex 1 (mTORC1) Enhances Bortezomib-induced Death in Tuberous Sclerosis Complex (TSC)-null Cells by a c-MYC-dependent Induction of the Unfolded Protein Response
inferredcites →https://doi.org/10.1074/jbc.m116.774471openalex-snapshot
Quantifying intracellular rates of glycolytic and oxidative ATP production and consumption using extracellular flux measurements
inferredcites →https://doi.org/10.1084/jem.20140341openalex-snapshot
Regulation of YAP by mTOR and autophagy reveals a therapeutic target of Tuberous Sclerosis Complex
inferredcites →https://doi.org/10.1086/316951openalex-snapshot
Mutational Analysis in a Cohort of 224 Tuberous Sclerosis Patients Indicates Increased Severity of TSC2, Compared with TSC1, Disease in Multiple Organs
inferredcites →https://doi.org/10.1089/lrb.2006.4.143openalex-snapshot
Vascular Endothelial Growth Factor-D Is Increased in Serum of Patients with Lymphangioleiomyomatosis
inferredcites →https://doi.org/10.1089/lrb.2009.0013openalex-snapshot
Animal Models of Lymphangioleiomyomatosis (LAM) and Tuberous Sclerosis Complex (TSC)
inferredcites →https://doi.org/10.1089/lrb.2009.0031openalex-snapshot
Lymphangioleiomyomatosis and TSC2 -/- Cells
inferredcites →https://doi.org/10.1089/omi.2011.0118openalex-snapshot
clusterProfiler: an R Package for Comparing Biological Themes Among Gene Clusters
inferredcites →https://doi.org/10.1093/bioinformatics/bty895openalex-snapshot
Heavy-tailed prior distributions for sequence count data: removing the noise and preserving large differences
inferredcites →https://doi.org/10.1093/hmg/ddu101openalex-snapshot
Neuronal Tsc1/2 complex controls autophagy through AMPK-dependent regulation of ULK1
inferredcites →https://doi.org/10.1093/hmg/ddy118openalex-snapshot
Metabolomic studies identify changes in transmethylation and polyamine metabolism in a brain-specific mouse model of tuberous sclerosis complex
inferredcites →https://doi.org/10.1093/nar/gkz369openalex-snapshot
g:Profiler: a web server for functional enrichment analysis and conversions of gene lists (2019 update)
inferredcites →https://doi.org/10.1097/gim.0b013e31803068c7openalex-snapshot
Genotype/phenotype correlation in 325 individuals referred for a diagnosis of tuberous sclerosis complex in the United States
inferredcites →https://doi.org/10.1101/784199openalex-snapshot
Identification of the Lymphangioleiomyomatosis Cell and Its Uterine Origin
inferredcites →https://doi.org/10.1101/gad.16750211openalex-snapshot
Tsc1 mutant neural stem/progenitor cells exhibit migration deficits and give rise to subependymal lesions in the lateral ventricle
inferredcites →https://doi.org/10.1101/gr.157586.113openalex-snapshot
Insights into neural crest development and evolution from genomic analysis
inferredcites →https://doi.org/10.1111/acel.12621openalex-snapshot
Reprogramming progeria fibroblasts re‐establishes a normal epigenetic landscape
inferredcites →https://doi.org/10.1126/science.aag3048openalex-snapshot
Lysosome activation clears aggregates and enhances quiescent neural stem cell activation during aging
inferredcites →https://doi.org/10.1126/science.aas9536openalex-snapshot
Spatiotemporal structure of cell fate decisions in murine neural crest
inferredcites →https://doi.org/10.1126/scitranslmed.3003840openalex-snapshot
Prevention of Alveolar Destruction and Airspace Enlargement in a Mouse Model of Pulmonary Lymphangioleiomyomatosis (LAM)
inferredcites →https://doi.org/10.1152/ajplung.00204.2003openalex-snapshot
Estradiol and tamoxifen stimulate LAM-associated angiomyolipoma cell growth and activate both genomic and nongenomic signaling pathways
inferredcites →https://doi.org/10.1152/ajprenal.00441.2011openalex-snapshot
Human TSC-associated renal angiomyolipoma cells are hypersensitive to ER stress
inferredcites →https://doi.org/10.1152/ajprenal.00569.2013openalex-snapshot
Evidence for pericyte origin of TSC-associated renal angiomyolipomas and implications for angiotensin receptor inhibition therapy
inferredcites →https://doi.org/10.1158/0008-5472.can-07-1356openalex-snapshot
TSC2 Loss in Lymphangioleiomyomatosis Cells Correlated with Expression of CD44v6, a Molecular Determinant of Metastasis
inferredcites →https://doi.org/10.1158/0008-5472.can-15-1287openalex-snapshot
Mesenchymal Tumorigenesis Driven by TSC2 Haploinsufficiency Requires HMGA2 and Is Independent of mTOR Pathway Activation
inferredcites →https://doi.org/10.1158/0008-5472.can-17-0925openalex-snapshot
Human Pluripotent Stem Cell–Derived TSC2 -Haploinsufficient Smooth Muscle Cells Recapitulate Features of Lymphangioleiomyomatosis
inferredcites →https://doi.org/10.1158/1541-7786.mcr-13-0258-topenalex-snapshot
Autophagy-Dependent Metabolic Reprogramming Sensitizes TSC2-Deficient Cells to the Antimetabolite 6-Aminonicotinamide
inferredcites →https://doi.org/10.1159/000320891openalex-snapshot
Tuberous Sclerosis Complex Renal Disease
inferredcites →https://doi.org/10.1164/ajrccm.164.4.2101154openalex-snapshot
Prevalence and Clinical Characteristics of Lymphangioleiomyomatosis (LAM) in Patients with Tuberous Sclerosis Complex
inferredcites →https://doi.org/10.1164/ajrccm.164.8.2104095openalex-snapshot
Chromosome 16 Loss of Heterozygosity in Tuberous Sclerosis and Sporadic Lymphangiomyomatosis
inferredcites →https://doi.org/10.1172/jci17222openalex-snapshot
Loss of Tsc1/Tsc2 activates mTOR and disrupts PI3K-Akt signaling through downregulation of PDGFR
inferredcites →https://doi.org/10.1172/jci44909openalex-snapshot
Single-cell Tsc1 knockout during corticogenesis generates tuber-like lesions and reduces seizure threshold in mice
inferredcites →https://doi.org/10.1172/jci58709openalex-snapshot
Lymphangioleiomyomatosis — a wolf in sheep’s clothing
inferredcites →https://doi.org/10.1172/jci7319openalex-snapshot
Tsc2+/– mice develop tumors in multiple sites that express gelsolin and are influenced by genetic background
inferredcites →https://doi.org/10.1177/1179069518795874openalex-snapshot
Enhancing Lysosomal Activation Restores Neural Stem Cell Function During Aging
inferredcites →https://doi.org/10.1186/s12974-016-0662-zopenalex-snapshot
Dysregulation of the (immuno)proteasome pathway in malformations of cortical development
inferredcites →https://doi.org/10.1186/s13023-017-0596-2openalex-snapshot
mTOR inhibitors in the pharmacologic management of tuberous sclerosis complex and their potential role in other rare neurodevelopmental disorders
inferredcites →https://doi.org/10.1186/s13059-014-0550-8openalex-snapshot
Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2
inferredcites →https://doi.org/10.1186/s13059-016-1012-2openalex-snapshot
Evaluation of off-target and on-target scoring algorithms and integration into the guide RNA selection tool CRISPOR
inferredcites →https://doi.org/10.1242/dmm.012096openalex-snapshot
Timing of mTOR activation affects tuberous sclerosis complex neuropathology in mouse models
inferredcites →https://doi.org/10.1371/journal.pcbi.1005896openalex-snapshot
Clustering gene expression time series data using an infinite Gaussian process mixture model
inferredcites →https://doi.org/10.1371/journal.pone.0023379openalex-snapshot
Multicenter Phase 2 Trial of Sirolimus for Tuberous Sclerosis: Kidney Angiomyolipomas and Other Tumors Regress and VEGF- D Levels Decrease
inferredcites →https://doi.org/10.1371/journal.pone.0031900openalex-snapshot
Therapeutic Trial of Metformin and Bortezomib in a Mouse Model of Tuberous Sclerosis Complex (TSC)
inferredcites →https://doi.org/10.1371/journal.pone.0098186openalex-snapshot
Efficient Mutagenesis by Cas9 Protein-Mediated Oligonucleotide Insertion and Large-Scale Assessment of Single-Guide RNAs
inferredcites →https://doi.org/10.1371/journal.pone.0152016openalex-snapshot
Determining Maximum Glycolytic Capacity Using Extracellular Flux Measurements
inferredcites →https://doi.org/10.1371/journal.pone.0197105openalex-snapshot
Rapamycin-independent IGF2 expression in Tsc2-null mouse embryo fibroblasts and human lymphangioleiomyomatosis cells
inferredcites →https://doi.org/10.1378/chest.14-0380openalex-snapshot
Antibody αPEP13h Reacts With Lymphangioleiomyomatosis Cells in Lung Nodules
inferredcites →https://doi.org/10.1513/pats.200705-061vsopenalex-snapshot
Smooth Muscle–like Cells in Pulmonary Lymphangioleiomyomatosis
inferredcites →https://doi.org/10.15252/embj.201593428openalex-snapshot
TFEB and TFE3 are novel components of the integrated stress response
inferredcites →https://doi.org/10.18632/oncotarget.26004openalex-snapshot
A new drug combination significantly reduces kidney tumor progression in kidney mouse model
inferredcites →https://doi.org/10.2353/ajpath.2009.090525openalex-snapshot
Melanoma-Associated Antigen Expression in Lymphangioleiomyomatosis Renders Tumor Cells Susceptible to Cytotoxic T Cells
inferredcites →https://doi.org/10.3389/fcell.2014.00069openalex-snapshot
The neural crest lineage as a driver of disease heterogeneity in Tuberous Sclerosis Complex and Lymphangioleiomyomatosis
inferredcites →https://doi.org/10.7554/elife.23202openalex-snapshot
Tsc2 disruption in mesenchymal progenitors results in tumors with vascular anomalies overexpressing Lgals3
inferredcites →https://doi.org/10.7554/elife.23202.041openalex-snapshot
Author response: Tsc2 disruption in mesenchymal progenitors results in tumors with vascular anomalies overexpressing Lgals3

What points at this work

Incoming claims: where this work appears in other papers’ reference lists and arguments.

inferred← citeshttps://doi.org/10.1016/b978-0-323-95730-4.00002-0openalex-snapshot
Extracellular matrix of the nervous system
inferred← citeshttps://doi.org/10.1016/j.celrep.2022.111048openalex-snapshot
Renal organoid modeling of tuberous sclerosis complex reveals lesion features arise from diverse developmental processes
inferred← citeshttps://doi.org/10.1016/j.crmeth.2025.101177openalex-snapshot
High-throughput bioprinting to produce micropatterned neuroepithelial tissues and model TSC2-deficient brain malformations
inferred← citeshttps://doi.org/10.1016/j.isci.2021.102684openalex-snapshot
Renal neoplasms in tuberous sclerosis mice are neurocristopathies
inferred← citeshttps://doi.org/10.1016/j.xpro.2023.102314openalex-snapshot
Differentiation and single-cell RNA-seq analyses of human pluripotent-stem-cell-derived renal organoids
inferred← citeshttps://doi.org/10.1101/2025.03.31.646426openalex-snapshot
A bioprinting approach for high-throughput production of micropatterned neuroepithelial tissues and modeling TSC2-deficient brain malformations
inferred← citeshttps://doi.org/10.1681/asn.0000000000000146openalex-snapshot
Tuberous Sclerosis Complex Kidney Lesion Pathogenesis: A Developmental Perspective
inferred← citeshttps://doi.org/10.2139/ssrn.5227917openalex-snapshot
A Bioprinting Approach for High-Throughput Production of Micropatterned Neuroepithelial Tissues And Modeling TSC2-Deficient Brain Malformations
inferred← citeshttps://doi.org/10.3389/fcell.2020.00591openalex-snapshot
Organelle Cooperation in Stem Cell Fate: Lysosomes as Emerging Regulators of Cell Identity
inferred← citeshttps://doi.org/10.3389/fcell.2022.887764openalex-snapshot
Beyond Genetics: The Role of Metabolism in Photoreceptor Survival, Development and Repair
inferred← citeshttps://doi.org/10.3389/fgeed.2021.630600openalex-snapshot
Genome Editing in iPSC-Based Neural Systems: From Disease Models to Future Therapeutic Strategies
inferred← citeshttps://doi.org/10.3389/fncel.2024.1478572openalex-snapshot
Advances in physiological and clinical relevance of hiPSC-derived brain models for precision medicine pipelines
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