tbuckley/cabot-search huggingface dataset:
Effect of Fine Particulate Matter on Allergic Skin Diseases in Children
Authors: Natthanan Ruangkijpaisal, Adithep Sawatchai, Potjanee Kiewngam, Wanlapa Jotikasthira, Ratchaneewan Sinitkul, Watcharoot Kanchongkittiphon, Wiparat Manuyakorn
Journal: Journal of Allergy and Clinical Immunology (2025)
Twice-Yearly Depemokimab Demonstrates an Acceptable Safety Profile in a 12-Month Interim Analysis of the AGILE Phase III Open-Label Extension Study
Authors: Daniel Jackson, Ian Pavord, Michael Wechsler, David Jackson, David Muccino, Natalia Karkoszka, Chang-Qinch Zhu, Paul Pfeffer
Journal: Journal of Allergy and Clinical Immunology (2025)
Efficacy And Safety Of Donidalorsen In Adolescent Patients With Hereditary Angioedema: A Subanalysis Of The Phase 3 OASIS-HAE Study
Authors: Joshua Jacobs, Marc Riedl, Laura Bordone, Kenneth Newman, Sabrina Treadwell, Sophie Wang, Aaron Yarlas, Danny Cohn
Journal: Journal of Allergy and Clinical Immunology (2025)
Single-cell RNA Sequencing Analysis of Human Group 2 Innate Lymphoid Cells in Chronic Rhinosinusitis with Nasal Polyps
Authors: Masanori Kidoguchi, Naruhito Iwasaki, Julie Poposki, Aiko Oka, Aiko Klingler, Lydia Suh, Junqin Bai, Whitney Stevens, Anju Peters, Leslie Grammer, Kevin Welch, Stephanie Smith, David Conley, Robert Schleimer, Robert Kern, Bruce Tan, Mitsuhiro Okano, Shigeharu Fujieda, Atsushi Kato
Journal: Journal of Allergy and Clinical Immunology (2025)
First-in-human VLP Peanut Vaccine Candidate: Safety and Tolerability Data from on-going Phase I/IIa Clinical Trial
Authors: Roxanne Oriel, Wayne Shreffler, Thomas Casale, Alexandra Santos, Christian Vogelberg, Edwin Kim, Mohamed Shamji, David Wilkie, Sema Eser, Chiara Zuiani, Sviatlana Starchenka, Peter Adura, Eamonn McArdle, Marietta Krebs, Lena Oppenlaender, Simon Hewings, Fiona Sellwood, Matthias Kramer, Anke Graessel, Murray Skinner, Pieter-Jan de Kam
Journal: Journal of Allergy and Clinical Immunology (2025)
Alternative Algorithm For Rapid E.coli L-asparaginase Desensitization Via Intramuscular Administration In Children With Acute Lymphoblastic Leukemia: A Single-Center Experience
Authors: Kokaew Chuaikaew, Araya Yuenyongviwat, Vanlaya Koosakulchai, Pasuree Sangsupawanich
Journal: Journal of Allergy and Clinical Immunology (2025)
Assessing Real-world Natural History of Indolent Systemic Mastocytosis: Retrospective Matched Cohort Study from Mayo Clinic Electronic Health Records
Authors: Thanai Pongdee, Dakota Powell, Taylor Weis, Robyn Scherber, Allison Smither, K. Purushotham, Katherine Carlson, Prerna Singh, Jamie Lo, Nivedita Rangarajan, Erin Sullivan, Hannah Barman
Journal: Journal of Allergy and Clinical Immunology (2025)
CRISPR-Based NTLA-2002 Improves Quality of Life in Patients With Hereditary Angioedema
Authors: Padmalal Gurugama, Danny Cohn, Markus Magerl, Constance Katelaris, David Maag, Mrinal Shah, Adele Golden, Shruti Nambiar, Hilary Longhurst
Journal: Journal of Allergy and Clinical Immunology (2025)
Racial and Ethnic Disparities and HIV Viral Load Among People Living with HIV During the Coronavirus-19 Pandemic in Brooklyn, New York
Authors: Jenelle Cocorpus, Susan Holman, Jessica Yager, Elizabeth Helzner, Mohsin Sardar, Stephan Kohlhoff, Tamar Smith-Norowitz
Journal: Journal of Allergy and Clinical Immunology (2025)
Hazelnut Oral Immunotherapy as a Treatment Option for Hazelnut Allergy and for Co-allergy to Walnut and Cashew (Nut CRACKER Study)
Authors: Arnon Elizur, Michael Appel, Liat Nachshon, Michael Levy, Naama Epstein-Rigbi, Yael Koren, Michael Goldberg
Journal: Journal of Allergy and Clinical Immunology (2025)
Dermatologic Adverse Events with Fitbit Use in a Physical Activity Intervention for Black
Authors: Wiktoria Kowalczyk, Aero Cavalier, Yi-Fan Chen, Ellen Davis, Spyros Kitsiou, Ebere Okpara, Karen Powell, Valerie Press, Deborah Salvo, Lisa Sharp, Lynette Smith, Brittani Wright, Sharmilee Nyenhuis
Journal: Journal of Allergy and Clinical Immunology (2025)
Clinicopathological features of major drug reaction with eosinophilia and systemic symptoms (DRESS): markers of disease severity in an HIV endemic setting.
Authors: Tafadzwa Chimbetete, Bukiwe Thwala, Phuti Choshi, Riyaadh Roberts, Elizabeth Phillips, Thuraya Isaacs, Rannakoe Lehloenya
Journal: Journal of Allergy and Clinical Immunology (2025)
Effectiveness of Sebetralstat for the On-demand Treatment of Laryngeal Hereditary Angioedema Attacks: Interim Analysis from KONFIDENT-S
Authors: Jonathan Bernstein, Emel Aygoren-Pursun, Vesna Grivcheva-Panovska, Inmaculada Martinez-Saguer, Danny Cohn, William Lumry, Marc Riedl, Andrea Zanichelli, James Hao, Michael Smith, Christopher Yea, Utpaul Audhya, Henriette Farkas
Journal: Journal of Allergy and Clinical Immunology (2025)
A Global Survey Evaluating Barriers To Prescribing Biologics For Atopic Diseases During Pregnancy
Authors: Sergio Chiarella, Divya Shah, Ishitha Jagadish, Leah Ishmael, Fnu Shakuntulla, Andrea Sitek, Maria Borghello, Isabel Fernandez de Alba, Barbara Kong-Cardoso, Duy Le Pham, Agnes Leung, Daria Levina, Shun Chi Ryan Lo, Matthew Norris, Nida Öztop, Thulja Trikamjee, Rosalaura Villareal-Gonzalez, Yichao Wang, Lyda Cuervo-Pardo, Marco Caminati, Razvigor Darlenski, Alexei Gonzalez-Estrada, Ivana Filipovic, Tu Trinh, Luciana Tanno
Journal: Journal of Allergy and Clinical Immunology (2025)
Artificial intelligence for direct-to-physician reporting of ambulatory electrocardiography
Authors: L. S. Johnson, P. Zadrozniak, G. Jasina, A. Grotek-Cuprjak, J. G. Andrade, E. Svennberg, S. Z. Diederichsen, W. F. McIntyre, S. Stavrakis, J. Benezet-Mazuecos, P. Krisai, Z. Iakobishvili, A. Laish-Farkash, S. Bhavnani, E. Ljungström, J. Bacevicius, N. L. van Vreeswijk, M. Rienstra, R. Spittler, J. A. Marx, A. Oraii, A. Miracle Blanco, A. Lozano, I. Mustafina, S. Zafeiropoulos, R. Bennett, J. Bisson, D. Linz, Y. Kogan, E. Glazer, G. Marincheva, M. Rahkovich, E. Shaked, M. H. Ruwald, K. Haugan, J. Węcławski, G. Radoslovich, S. Jamal, A. Brandes, P. T. Matusik, M. Manninger, P. B. Meyre, S. Blum, A. Persson, A. Måneheim, P. Hammarlund, A. Fedorowski, T. Wodaje, C. Lewinter, V. Juknevicius, R. Jakaite, C. Shen, T. Glotzer, P. Platonov, G. Engström, A. P. Benz, J. S. Healey
Journal: Nature Medicine (2025)
A potent epigenetic editor targeting human PCSK9 for durable reduction of low-density lipoprotein cholesterol levels
Authors: Frederic Tremblay, Qiang Xiong, Shrijal S Shah, Chih-Wei Ko, Kenneth Kelly, Mary S Morrison, Cristiana Giancarlo, Ricardo N Ramirez, Erica M Hildebrand, Sarah B Voytek, Gabriel K El Sebae, Shane H Wright, Liam Lofgren, Scott Clarkson, Christine Waters, Samantha J Linder, Songlei Liu, Taesun Eom, Shefal Parikh, Yuki Weber, Salette Martinez, Padma Malyala, Sahar Abubucker, Ari E Friedland, Morgan L Maeder, Angelo Lombardo, Vic E Myer, Aron B Jaffe
Journal: Nature Medicine (2025)

Epigenetic editing holds the promise of durable therapeutic effects by silencing disease-causing genes without changing the underlying DNA sequence. In this study, we designed an epigenetic editor to target human PCSK9 and thereby induce DNA methylation at this locus. A single administration of lipid nanoparticles encapsulating mRNA encoding this epigenetic editor was sufficient to drive near-complete silencing of human PCSK9 in transgenic mice. Silencing was durable for at least 1 year and was fully maintained after partial hepatectomy-induced liver regeneration. In addition, we showed reversibility of epigenetic editing in mice with previously silenced PCSK9 upon treatment with a targeted epigenetic activator designed to demethylate the PCSK9 locus. Notably, in cynomolgus monkeys, a single administration of the epigenetic editor potently and durably decreased circulating PCSK9 protein levels by approximately 90% with concomitant reduction in low-density lipoprotein cholesterol levels by approximately 70%. These findings demonstrate the therapeutic potential of durable and reversible epigenetic editing in vivo and support the development of epigenetic editor-based treatment for hypercholesterolemia.
Upper Airway Microbiome Interactions with GSDMB and ORMDL3 Asthma Risk Genes Influence Early Life Wheeze Outcomes
Authors: Holly Steininger, Kathryn McCauley, Kristine Lee, Agustin Calatroni, Kathryn Holt, Michael Inouye, Robert Wood, George O'Connor, Leonard Bacharier, Meyer Kattan, Robert Lemanske, Daniel Jackson, James Gern, Carole Ober, Susan Lynch, Douglas Fadrosh, Kole Lynch, Matthew Dapas, Andreanne Morin, Katherine Rivera-Spoljaric
Journal: Journal of Allergy and Clinical Immunology (2025)
Long-Term Efficacy Results of Epicutaneous Immunotherapy With VIASKIN® Peanut Patch in Peanut-Allergic Children Aged 4-11 Years in the Phase 3 PEOPLE Study
Authors: David Fleischer, Lara Ford, Roxanne Oriel, Peter Smith, Gordon Sussman, William Yang, Timothée Bois, Jonas Meney, Hugh Sampson
Journal: Journal of Allergy and Clinical Immunology (2025)
Predictive Modelling for Allergic Rhinitis: A Real-World Study on the Association Between Level of Allergens and Symptoms Occurrence &amp; Severity
Authors: David Peden, Gennaro D’Amato, Margarita Murrieta-Aguttes, Yongbin Yang, Bruno Scarpellini, Sabine Tong, Andrew Stewart
Journal: Journal of Allergy and Clinical Immunology (2025)
Real-World Effectiveness of Dupilumab Through 18 Months in Patients with CRSwNP and AERD: Results from the Global AROMA Registry
Authors: Andrew White, Kathleen Buchheit, Tanya Laidlaw, Enrico Heffler, Marjolein Cornet, Changming Xia, Helen Kim, Mark Corbett, Juby Jacob-nara, Amr Radwan
Journal: Journal of Allergy and Clinical Immunology (2025)
Understanding the Role of Pollution Sources in Intracity Racial and Ethnic Health Disparities: Proximity to Semiconductor Facilities, Neighborhood Demographic Characteristics, and Asthma-related Emergency Department Visits
Authors: Sarah Chambliss, Corwin Zigler, Aquiel Warner, Catherine Cubbin, Elizabeth Mueller, Roger Peng, Elizabeth Matsui
Journal: Journal of Allergy and Clinical Immunology (2025)
Disparities in the ICD-10 Coding of Hypogammaglobulinemia by Race, Ethnicity, and Hypogammaglobulinemia Severity
Authors: Joseph Hong, Lingxiao Zhang, Baijun Zhou, Andrew Pak, Katherine Liu, Ahmed Elmoursi, Mei-Sing Ong, Jocelyn Farmer, Sara Barmettler
Journal: Journal of Allergy and Clinical Immunology (2025)
Multi-omics analysis in primary T cells elucidates mechanisms behind disease-associated genetic loci
Authors: Chenfu Shi, Danyun Zhao, Jake Butler, Antonios Frantzeskos, Stefano Rossi, James Ding, Carlo Ferrazzano, Charlotte Wynn, Ryan Malcolm Hum, Ellie Richards, Muskan Gupta, Khadijah Patel, Chuan Fu Yap, Darren Plant, Richard Grencis, Paul Martin, Antony Adamson, Stephen Eyre, John Bowes, Anne Barton, Pauline Ho, Magnus Rattray, Gisela Orozco
Journal: Genome biology (2025)

Genome-wide association studies (GWAS) have uncovered the genetic basis behind many diseases and conditions. However, most of these genetic loci affect regulatory regions, making the interpretation challenging. Chromatin conformation has a fundamental role in gene regulation and is frequently used to associate potential target genes to regulatory regions. However, previous studies mostly used small sample sizes and immortalized cell lines instead of primary cells. Here we present the most extensive dataset of chromatin conformation with matching gene expression and chromatin accessibility from primary CD4+ and CD8+ T cells to date, isolated from psoriatic arthritis patients and healthy controls. We generated 108 Hi-C libraries (49 billion reads), 128 RNA-seq libraries and 126 ATAC-seq libraries. These data enhance our understanding of the mechanisms by which GWAS variants impact gene regulation, revealing how genetic variation alters chromatin accessibility and structure in primary cells at an unprecedented scale. We refine the mapping of GWAS loci to implicated regulatory elements, such as CTCF binding sites and other enhancer elements, aiding gene assignment. We uncover BCL2L11 as the probable causal gene within the rheumatoid arthritis (RA) locus rs13396472, despite the GWAS variants' intronic positioning relative to ACOXL, and we identify mechanisms involving SESN3 dysregulation in the RA locus rs4409785. Given these genes' significant role in T cell development and maturation, our work deepens our comprehension of autoimmune disease pathogenesis, suggesting potential treatment targets. In addition, our dataset provides a valuable resource for the investigation of immune-mediated diseases and gene regulatory mechanisms.
Impact of SMART with Budesonide and Formoterol vs. Traditional Asthma Therapy with Fluticasone and Salmeterol on COVID-19 Severity: A Retrospective Cohort Study
Authors: Yunjie Li, Wansu Chen, Rebecca Hill, Jing Zhang, Rebecca Gambatese, Peter Huynh
Journal: Journal of Allergy and Clinical Immunology (2025)
Correlation between nasal tissue and brushing sample transcriptomics in CRSwNP and controls
Authors: Daiki Nakashima, Natsuki Inoue, Mamoru Yoshikawa, Eri Mori, Nobuyoshi Otori, Hiromi Kojima, Mayumi Tamari, Tsuguhisa Nakayama, Tomomitsu Hirota
Journal: Journal of Allergy and Clinical Immunology (2025)
Latent circuit inference from heterogeneous neural responses during cognitive tasks
Authors: Christopher Langdon, Tatiana A Engel
Journal: Nature Neuroscience (2025)

Higher cortical areas carry a wide range of sensory, cognitive and motor signals mixed in heterogeneous responses of single neurons tuned to multiple task variables. Dimensionality reduction methods that rely on correlations between neural activity and task variables leave unknown how heterogeneous responses arise from connectivity to drive behavior. We develop the latent circuit model, a dimensionality reduction approach in which task variables interact via low-dimensional recurrent connectivity to produce behavioral output. We apply the latent circuit inference to recurrent neural networks trained to perform a context-dependent decision-making task and find a suppression mechanism in which contextual representations inhibit irrelevant sensory responses. We validate this mechanism by confirming the behavioral effects of patterned connectivity perturbations predicted by the latent circuit model. We find similar suppression of irrelevant sensory responses in the prefrontal cortex of monkeys performing the same task. We show that incorporating causal interactions among task variables is critical for identifying behaviorally relevant computations from neural response data.
Interpersonal Variation in Gut Microbiota Structure Modulates Individual-Specific Immune Responses to Vibrio cholerae
Authors: Elyza Do, Jasmin Akter, John Macbeth, Orion Brock, Varadh Piamthai, Rashidul Haque, Ana Weil, Philip Ahern, Ansel Hsiao
Journal: Journal of Allergy and Clinical Immunology (2025)
The need for methacholine challenge test to confirm asthma diagnosis among symptomatic overweight/obese patients with asthma
Authors: Lale Ertuglu, Alessandra Tomasello, Leonard Bacharier, Pingsheng Wu, Elizaveta Kalaidina, Patrice Becker, Caeden Dempsey, Stokes Peebles, Kevin Niswender, Gordon Bernard, Katherine Cahill
Journal: Journal of Allergy and Clinical Immunology (2025)
Association of Host CDHR3 rs6967330 Genotype with Rhinovirus Infections in Children from 1997-2018
Authors: Yingyu Gao, Timothy Choi, Mark Devries, Kaitlin Tetreault, Ronald Gangnon, Leonard Bacharier, William Busse, Carlos Camargo, Robyn Cohen, Gregory DeMuri, Anne Fitzpatrick, Peter Gergen, Kristine Grindle, Rebecca Gruchalla, Tina Hartert, Kohei Hasegawa, Gurjit Khurana Hershey, Patrick Holt, Kiara Homil, Tuomas Jartti, Meyer Kattan, Carolyn Kercsmar, Haejin Kim, Ingrid Laing, Peter Le Souef, Andrew Liu, David Mauger, Tressa Pappas, Kristine Lee, Shilpa Patel, Wanda Phipatanakul, Jacqueline Pongracic, Christine Seroogy, Peter Sly, Christopher Tisler, Ellen Wald, Robert Wood, Robert Lemanske, Daniel Jackson, Yury Bochkov, James Gern, Jo Wilson
Journal: Journal of Allergy and Clinical Immunology (2025)
The utility of dynamic chest radiography in patients with asthma, COPD, COVID-19 and ILD: A pilot study
Authors: Ryan E Robinson, Fred Fyles, Rachel C Burton, Amy Nuttall, Karl Hunter, Thomas S FitzMaurice, Reynaldo Martina, Diana Penha, Ram L Bedi, Hassan Burhan
Journal: Pulmonology (2025)

Assessment of breathlessness requires a combination of imaging and lung function testing. Dynamic digital radiography (DDR) of the thorax is an imaging technique that allows physiological and anatomical information to be gathered at the time of chest X-ray and has the potential to significantly streamline diagnostic pathways. The aims of this study were to investigate the acceptability of DDR to patients and explore the correlation between DDR-derived measurements with lung volumes measured using full pulmonary function tests (PFT). We conducted a single-centre, prospective, pilot study of patients with confirmed asthma, chronic obstructive pulmonary disease (COPD), interstitial lung disease (ILD) or post-COVID-19 infection. Participants underwent DDR and paired PFT between March 2021 and August 2022. Dynamic digital radiography acceptability was measured using a 10-cm visual analogue scale (VAS). Point estimates and exact confidence intervals were used to evaluate participant preference. Digital dynamic radiography would be considered acceptable if the lower bound of the 95% confidence interval (exact) is greater than 50%. Pearson correlation (r) was used to explore associations between DDR measurements and PFT parameters. 40 participants (asthma, n = 11; COPD, n = 9; ILD, n = 11; post-COVID, n = 9) had DDR with adequate image acquisition and PFT. Mean age of participants was 63.38 years (standard deviation 14.89) and 63% were male (25/40). The lower 95% confidence interval threshold for VAS acceptability was 92% for all groups combined and considered acceptable. The projected lung area at end inspiration (PLAinsp) closely correlated with total lung capacity across all disease cohorts (r = 0.80, p < 0.001) and projected lung area at end expiration (PLAexp) was strongly correlated with residual volume in airways disease (COPD: r = 0.87, p = 0.003; asthma: r = 0.85, p = 0.002). Dynamic digital radiography is an acceptable investigation for respiratory patients. DDR-derived measurements correlate with lung volumes obtained from PFTs. Larger studies are required to validate DDR as a possible method to identify and monitor air trapping in airways disease, allowing early detection and assessment of treatment effectiveness.
Long-read sequencing and genome assembly of natural history collection samples and challenging specimens
Authors: Bernhard Bein, Ioannis Chrysostomakis, Larissa S Arantes, Tom Brown, Charlotte Gerheim, Tilman Schell, Clément Schneider, Evgeny Leushkin, Zeyuan Chen, Julia Sigwart, Vanessa Gonzalez, Nur Leena W S Wong, Fabricio R Santos, Mozes P K Blom, Frieder Mayer, Camila J Mazzoni, Astrid Böhne, Sylke Winkler, Carola Greve, Michael Hiller
Journal: Genome biology (2025)

Museum collections harbor millions of samples, largely unutilized for long-read sequencing. Here, we use ethanol-preserved samples containing kilobase-sized DNA to show that amplification-free protocols can yield contiguous genome assemblies. Additionally, using a modified amplification-based protocol, employing an alternative polymerase to overcome PCR bias, we assemble the 3.1 Gb maned sloth genome, surpassing the previous 500 Mb protocol size limit. Our protocol also improves assemblies of other difficult-to-sequence molluscs and arthropods, including millimeter-sized organisms. By highlighting collections as valuable sample resources and facilitating genome assembly of tiny and challenging organisms, our study advances efforts to obtain reference genomes of all eukaryotes.
Phospho-tau serine-262 and serine-356 as biomarkers of pre-tangle soluble tau assemblies in Alzheimer’s disease
Authors: Tohidul Islam, Emily Hill, Eric E Abrahamson, Stijn Servaes, Denis S Smirnov, Xuemei Zeng, Anuradha Sehrawat, Yijun Chen, Przemysław R Kac, Hlin Kvartsberg, Maria Olsson, Emma Sjons, Fernando Gonzalez-Ortiz, Joseph Therriault, Cécile Tissot, Ivana Del Popolo, Nesrine Rahmouni, Abbie Richardson, Victoria Mitchell, Henrik Zetterberg, Tharick A Pascoal, Tammaryn Lashley, Mark J Wall, Douglas Galasko, Pedro Rosa-Neto, Milos D Ikonomovic, Kaj Blennow, Thomas K Karikari
Journal: Nature Medicine (2025)

Patients with Alzheimer's disease (AD) with little or no quantifiable insoluble brain tau neurofibrillary tangle (NFT) pathology demonstrate stronger clinical benefits of therapies than those with advanced NFTs. The formation of NFTs can be prevented by targeting the intermediate soluble tau assemblies (STAs). However, biochemical understanding and biomarkers of STAs are lacking. We show that Tris-buffered saline-soluble tau aggregates from autopsy-verified AD brain tissues include the core sequence ~tau258-368. In neuropathological assessments, antibodies against the phosphorylation sites serine-262 and serine-356 within the STA core almost exclusively stained granular (that is, prefibrillar) tau aggregates in pre-NFTs while antibodies against phosphorylation at serine-202 and threonine-205 and threonine-231, outside the STA core, stained the entire spectrum of tau aggregates in pre-NFTs and mature NFTs, dystrophic neurites and neuropil threads in the hippocampus. Functionally, a recombinantly produced STA core peptide robustly altered neuronal excitability and synaptic transmission in mouse hippocampal brain slices. Furthermore, we developed a cerebrospinal fluid assay that differentiated STAs in AD from non-AD tauopathies, correlated with the severity of NFT burden and cognitive decline independently of amyloid beta deposition, and with tau positron emission tomography uptake across Braak NFT stages. Together, our findings inform about the status of early-stage tau aggregation, reveal aggregation-relevant phosphorylation epitopes in tau and offer a diagnostic biomarker and targeted therapeutic opportunities for AD.
Exploring Origin-Dependent Susceptibility of Smooth Muscle Cells to Aortic Diseases Through Intersectional Genetics
Authors: Ximeng Han, Yi Li, Enci Wang, Huan Zhu, Xiuzhen Huang, Wenjuan Pu, Mingjun Zhang, Kuo Liu, Huan Zhao, Zixin Liu, Yufei Zhao, Linghong Shen, Yan Li, Xiao Yang, Qing-Dong Wang, Xin Ma, Ruling Shen, Kathy Lui, Lixin Wang, Ben He, Bin Zhou
Journal: Circulation (2025)

BACKGROUND: The developmental diversity among smooth muscle cells (SMCs) plays a crucial role in segment-specific aortic diseases. However, traditional genetic approaches are inadequate for enabling in vivo analysis of disease susceptibility associated with cellular origin. There is an urgent need to build genetic technologies that target different developmental origins to investigate the mechanisms of aortopathies, thereby facilitating the development of effective therapeutics. METHODS: To address this challenge, we developed an advanced dual recombinase-mediated intersectional genetic system, specifically designed to precisely target SMCs from various developmental origins in mice. Specifically, we used Isl1-Dre , Wnt1-Dre , Meox1-DreER , and Upk3b-Dre to target SMC progenitors from the second heart field, cardiac neural crest, somites, and mesothelium, respectively. This system was combined with single-cell RNA sequencing to investigate the impact of TGF-β (transforming growth factor-β) signaling in different segments of the aorta by selectively knocking out Tgfbr2 in the ascending aorta and Smad4 in the aortic arch, respectively. RESULTS: Through intersectional genetic approaches, we use the Myh11-Cre(ER ) driver along with origin-specific Dre drivers to trace cells of diverse developmental origins within the SMC population. We found that a deficiency of Tgfbr2 in SMCs of the ascending aorta leads to aneurysm formation in this specific region. We also demonstrate the critical role of Smad4 in preserving aortic wall integrity and homeostasis in SMCs of the aortic arch. CONCLUSIONS: Our approach to genetically targeting SMC subtypes provides a novel platform for exploring origin-dependent or location-specific aortic vascular diseases. This genetic system enables comprehensive analysis of contributions from different cell lineages to SMC behavior and pathology, thereby paving the way for targeted research and therapeutic interventions in the future.