ArticleDevelopmental cell2022
R-SPONDIN2
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Article in Developmental cell, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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28citing papers in PubMed
4.7field-weighted citation impact, top 4% of its field
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Who cites it
28 citing papers in PubMed, 35 citations in OpenAlex.
- Extracellular matrix stiffness directs region-specific lung epithelial differentiation revealed by hPSC-derived lung organoids.Nature communications · 2026Article
- Defective alveolar regeneration in emphysema: identifying dysfunctional cellular crosstalk and novel therapeutic opportunities for tissue repair.European respiratory review : an official journal of the European Respiratory Society · 2026Review
- Bidirectional fibrogenic cross-talk revealed in a human iPSC-derived epithelial-mesenchymal co-culture model of pulmonary fibrosis.bioRxiv : the preprint server for biology · 2026Article
- Research Advances and Disease Modeling in Respiratory Organoids.Biomedicines · 2026Review
- An hiPSC-derived multi-lineage lung model exhibiting proximal-distal epithelial features for modeling pulmonary fibrosis.Frontiers in cell and developmental biology · 2026Article
- Transcriptional coordination in multicellular lineage differentiation during lung organogenesis: deciphering the role of epithelial cells as a microenvironmental regulatory hub.Frontiers in cell and developmental biology · 2026Review
- Transcriptomic decoding of regional cortical vulnerability to drug-resistant epilepsy using 7T MRI.Communications biology · 2025Article
- Applications of human lung organoids to human respiratory virus research: advances, limitations and future directions.Infection · 2025Review
- Novel Porcine Model Reveals Two Distinct LGR5 Cell Types during Lung Development and Homeostasis.American journal of respiratory cell and molecular biology · 2025Article
- [Role of R-spondin 2 on osteogenic differentiation of bone marrow mesenchymal stem cells and bone metabolism in ovariectomized mice].Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery · 2024Article
- Article
- RSPO2 as Wnt signaling enabler: Important roles in cancer development and therapeutic opportunities.Genes & diseases · 2024Review
- Recent advances in lung organoid development and applications in disease modeling.The Journal of clinical investigation · 2023Review
- Opposing roles for TGFβ- and BMP-signaling during nascent alveolar differentiation in the developing human lung.NPJ Regenerative medicine · 2023Article
- The lung mesenchyme in development, regeneration, and fibrosis.The Journal of clinical investigation · 2023Review
- Regionally distinct progenitor cells in the lower airway give rise to neuroendocrine and multiciliated cells in the developing human lung.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- FGF18 promotes human lung branching morphogenesis through regulating mesenchymal progenitor cells.American journal of physiology. Lung cellular and molecular physiology · 2023Article
- Gene expression in organoids: an expanding horizon.Biology direct · 2023Review
- A topographic atlas defines developmental origins of cell heterogeneity in the human embryonic lung.Nature cell biology · 2023Article
- Multipotent Embryonic Lung Progenitors: Foundational Units of In Vitro and In Vivo Lung Organogenesis.Advances in experimental medicine and biology · 2023Article
Corrections and comments
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Authors and funding
15 authors at 5 institutions in 3 countries.
Renee F C HeinDepartment of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Joshua H WuDepartment of Internal Medicine, Gastroenterology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Emily M HollowayDepartment of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Tristan FrumDepartment of Internal Medicine, Gastroenterology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Ansley S ConcholaProgram in Cell and Molecular Biology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Yu-Hwai TsaiDepartment of Internal Medicine, Gastroenterology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Angeline WuDepartment of Internal Medicine, Gastroenterology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Alexis S FineDepartment of Internal Medicine, Gastroenterology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Alyssa J MillerProgram in Cell and Molecular Biology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Emmanuelle Szenker-RaviLaboratory of Human Genetics & Therapeutics, Genome Institute of Singapore, A(∗)STAR, Singapore 138648, Singapore.
Kelley S YanColumbia Center for Human Development, Columbia Stem Cell Initiative, Departments of Medicine and Genetics and Development, Columbia University Irving Medical Center, New York, NY 10032, USA.
Calvin J KuoDepartment of Medicine, Division of Hematology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Ian GlassDepartment of Pediatrics, Genetic Medicine, University of Washington, Seattle, WA 98195, USA.
Bruno ReversadeLaboratory of Human Genetics & Therapeutics, Genome Institute of Singapore, A(∗)STAR, Singapore 138648, Singapore; Laboratory of Human Genetics & Therapeutics, Institute of Molecular and Cell Biology (IMCB), A∗STAR, Singapore; Medical Genetics Department, Koç University School of Medicine (KUSOM), Istanbul, Turkey.
Jason R SpenceDepartment of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Department of Internal Medicine, Gastroenterology, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Program in Cell and Molecular Biology, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Department of Biomedical Engineering, University of Michigan College of Engineering, Ann Arbor, MI 48109, USA. Electronic address: spencejr@umich.edu.
University of Michigan · USAgency for Science, Technology and Research · SGColumbia University · USStanford University · USUniversity of Washington · US
Funding
MICHIGAN MEDICAL SCIENTIST TRAINING PROGRAMT32GM007863 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI COLLINS, KATHLEEN L. · 1985 to 2024
$38.3MTissue Engineering and RegenerationT32DE007057 · NIDCR · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI DAVID H. KOHN · 1985 to 2026
$17.3MLABORATORY OF DEVELOPMENTAL BIOLOGYR24HD000836 · NICHD · UNIVERSITY OF WASHINGTON · PI Ian Amos Glass · 1995 to 2026
$16.9MSupplement to a Hox-Wnt-Sox signaling axis regulates lung development, patterning and branchingR01HL119215 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI SPENCE, JASON · 2013 to 2021
$4.2MCellular and Molecular Biology at MichiganT32GM145470 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI John Chadwick Brenner · 2022 to 2026
$4.1MCellular Biotechnology Training Program (CBTP) - Years 31-35T32GM145304 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Guizhi Zhu · 2022 to 2026
$2.6MDirecting Cell Fate Along the Intestinal Enteroendocrine LineageDP2DK128801 · NIDDK · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI YAN, KELLEY · 2020 to 2020
$2.4MIntestinal Stem Cell Function During Aging and Tumor InitiationR01AG067014 · NIA · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI YAN, KELLEY · 2020 to 2024
$2.3MInvestigating the role of mesenchymal R-Spondin2 during human lung developmentF31HL152531 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI CONWAY, RENEE FRANCES · 2020 to 2022
$110kInvestigating organ-specific patterning of the vasculature during human developmentF31HL146162 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI HOLLOWAY, EMILY MARIE · 2019 to 2020
$74kMechanisms of basal cell differentiation during murine and human lung developmentF31HL142197 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI MILLER, ALYSSA JANE · 2018 to 2019
$57kNHLBI NIH HHS F31 HL142197NHLBI NIH HHS F31 HL146162NHLBI NIH HHS F31 HL152531NHLBI NIH HHS R01 HL119215NIA NIH HHS R01 AG067014NICHD NIH HHS R24 HD000836NIDCR NIH HHS T32 DE007057NIDDK NIH HHS DP2 DK128801NIGMS NIH HHS T32 GM007863NIGMS NIH HHS T32 GM145304NIGMS NIH HHS T32 GM145470
Abstract
The human respiratory epithelium is derived from a progenitor cell in the distal buds of the developing lung. These "bud tip progenitors" are regulated by reciprocal signaling with surrounding mesenchyme; however, mesenchymal heterogeneity and function in the developing human lung are poorly understood. We interrogated single-cell RNA sequencing data from multiple human lung specimens and identified a mesenchymal cell population present during development that is highly enriched for expression of the WNT agonist RSPO2, and we found that the adjacent bud tip progenitors are enriched for the RSPO2 receptor LGR5. Functional experiments using organoid models, explant cultures, and FACS-isolated RSPO2
Indexed as
Mesenchymal Stem CellsOrganogenesisHumansLungOrganoidsWnt Signaling Pathwaybud tip progenitorhuman developmentlung developmentlung mesenchymelung organoidmesenchymal cellRSPO2R-Spondin2single-cell RNA-seqstem cell niche
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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.