ArticleCell stem cell2020
Organoids Model Transcriptional Hallmarks of Oncogenic KRAS Activation in Lung Epithelial Progenitor Cells.
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Article in Cell stem cell, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 107 papers, 1 of them a synthesis that pooled it.
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107citing papers in PubMed, 1 pooled it
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Who cites it
107 citing papers in PubMed, 1 synthesis or guideline pooled it, 164 citations in OpenAlex.
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- Renal cell carcinoma organoids for precision medicine: bridging the gap between models and patients.Journal of translational medicine · 2025Review
47 more citing papers are in PubMed but not listed here.
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Authors and funding
26 authors at 5 institutions in 1 country.
Antonella F M DostStem Cell Program and Divisions of Hematology/Oncology and Pulmonary Medicine, Boston Children's Hospital, Boston, MA 02115, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
Aaron L MoyeStem Cell Program and Divisions of Hematology/Oncology and Pulmonary Medicine, Boston Children's Hospital, Boston, MA 02115, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
Marall VedaieCenter for Regenerative Medicine of Boston University and Boston Medical Center, Boston, MA 02118, USA; The Pulmonary Center and Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA.
Linh M TranDepartment of Medicine, David Geffen School of Medicine at UCLA, University of California, Los Angeles, Los Angeles, CA, USA.
Eileen FungDepartment of Surgery, David Geffen School of Medicine at UCLA, University of California, Los Angeles, Los Angeles, CA, USA.
Dar HeinzeCenter for Regenerative Medicine of Boston University and Boston Medical Center, Boston, MA 02118, USA; Section of Gastroenterology and Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA.
Carlos Villacorta-MartinCenter for Regenerative Medicine of Boston University and Boston Medical Center, Boston, MA 02118, USA.
Jessie HuangCenter for Regenerative Medicine of Boston University and Boston Medical Center, Boston, MA 02118, USA; The Pulmonary Center and Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA.
Ryan HekmanCenter for Network Systems Biology, Boston University, Boston, MA 02118, USA; Department of Biochemistry, Boston University School of Medicine, Boston, MA 02118, USA.
Julian H KwanCenter for Network Systems Biology, Boston University, Boston, MA 02118, USA; Department of Biochemistry, Boston University School of Medicine, Boston, MA 02118, USA.
Benjamin C BlumCenter for Network Systems Biology, Boston University, Boston, MA 02118, USA; Department of Biochemistry, Boston University School of Medicine, Boston, MA 02118, USA.
Sharon M LouieStem Cell Program and Divisions of Hematology/Oncology and Pulmonary Medicine, Boston Children's Hospital, Boston, MA 02115, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
Samuel P RowbothamStem Cell Program and Divisions of Hematology/Oncology and Pulmonary Medicine, Boston Children's Hospital, Boston, MA 02115, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
Julio Sainz de AjaStem Cell Program and Divisions of Hematology/Oncology and Pulmonary Medicine, Boston Children's Hospital, Boston, MA 02115, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
Mary E PiperHarvard T.H. Chan School of Public Health, Department of Biostatistics, Boston, MA 02115, USA.
Preetida J BhetariyaStem Cell Program and Divisions of Hematology/Oncology and Pulmonary Medicine, Boston Children's Hospital, Boston, MA 02115, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA; Harvard T.H. Chan School of Public Health, Department of Biostatistics, Boston, MA 02115, USA.
Roderick T BronsonRodent Histopathology Core, Harvard Medical School, Boston, MA 02115, USA.
Andrew EmiliCenter for Network Systems Biology, Boston University, Boston, MA 02118, USA; Department of Biochemistry, Boston University School of Medicine, Boston, MA 02118, USA; Department of Biology, Boston University, Boston, MA 02215, USA.
Gustavo MostoslavskyCenter for Regenerative Medicine of Boston University and Boston Medical Center, Boston, MA 02118, USA; Section of Gastroenterology and Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA.
Gregory A FishbeinDepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, University of California, Los Angeles, Los Angeles, CA 90095, USA.
William D WallaceDepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Pathology, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA 90033, USA.
Kostyantyn KrysanDepartment of Medicine, David Geffen School of Medicine at UCLA, University of California, Los Angeles, Los Angeles, CA, USA.
Steven M DubinettDepartment of Medicine, David Geffen School of Medicine at UCLA, University of California, Los Angeles, Los Angeles, CA, USA; Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Jane YanagawaDepartment of Surgery, David Geffen School of Medicine at UCLA, University of California, Los Angeles, Los Angeles, CA, USA; Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address: jyanagawa@mednet.ucla.edu.
Darrell N KottonCenter for Regenerative Medicine of Boston University and Boston Medical Center, Boston, MA 02118, USA; The Pulmonary Center and Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA. Electronic address: dkotton@bu.edu.
Carla F KimStem Cell Program and Divisions of Hematology/Oncology and Pulmonary Medicine, Boston Children's Hospital, Boston, MA 02115, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA. Electronic address: carla.kim@childrens.harvard.edu.
Boston University · USBoston Children's Hospital · USUniversity of California, Los Angeles · USHarvard University · USUniversity of Southern California · US
Funding
Microenvironmental control of progenitors in organ dysfunction and repairU01HL100402 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI KIM, CARLA F., SCADDEN, DAVID T · 2009 to 2015
$8.5MEditing Alveolar Progenitor Cells for Correction of Monogenic DiseaseU01HL134745 · NHLBI · CINCINNATI CHILDRENS HOSP MED CTR · PI KOTTON, DARRELL N., MORRISEY, EDWARD E · 2016 to 2022
$8.3MEpithelial stem/progenitor cells as repair agents in diffuse alveolar damageU01HL134766 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CHAPMAN, HAROLD A, KOTTON, DARRELL N. · 2016 to 2022
$8.1MDerivation of Transplantable Lung Epithelial Progenitors from iPS CellsR01HL095993 · NHLBI · BOSTON UNIVERSITY MEDICAL CAMPUS · PI Darrell N. Kotton · 2009 to 2026
$7.5MIntegrated Molecular, Cellular, and Imaging Characterization of Screen-Detected Lung CancerU01CA196408 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ABERLE, DENISE R., DUBINETT, STEVEN M. · 2015 to 2021
$7.1MCell-cell interactions governing lung epithelial progenitor cellsR35HL150876 · NHLBI · BOSTON CHILDREN'S HOSPITAL · PI Carla F. Kim · 2020 to 2026
$6.2MA National iPS Cell Network with Deep Phenotyping for Translational ResearchU01TR001810 · NCATS · BOSTON UNIVERSITY MEDICAL CAMPUS · PI GILAD, YOAV, KOTTON, DARRELL N. · 2016 to 2020
$4.4MA National Resource for Lung disease-specific iPS cellsR24HL123828 · NHLBI · BOSTON UNIVERSITY MEDICAL CAMPUS · PI KOTTON, DARRELL N., MOSTOSLAVSKY, GUSTAVO · 2014 to 2018
$2.7MEpigenenomic and transcriptomic networks in normal and defective lung developmentR01HL128172 · NHLBI · BOSTON UNIVERSITY MEDICAL CAMPUS · PI KOTTON, DARRELL N. · 2015 to 2018
$2.2MIn Vivo and In Vitro Characterization of Bronchio-Alveolar Stem CellsR01HL090136 · NHLBI · BOSTON CHILDREN'S HOSPITAL · PI KIM, CARLA F. · 2007 to 2010
$1.9MSignaling pathways in lung stem cell differentiationR01HL125821 · NHLBI · BOSTON CHILDREN'S HOSPITAL · PI KIM, CARLA F. · 2015 to 2018
$1.8MMechanisms of Thrombospondin-1 as a pulmonary vascular mediatorR01HL132266 · NHLBI · BOSTON CHILDREN'S HOSPITAL · PI KIM, CARLA F. · 2017 to 2020
$1.6MNCATS NIH HHS U01 TR001810NCI NIH HHS U01 CA196408NHLBI NIH HHS R01 HL090136NHLBI NIH HHS R01 HL095993NHLBI NIH HHS R01 HL122442NHLBI NIH HHS R01 HL125821NHLBI NIH HHS R01 HL128172NHLBI NIH HHS R01 HL132266NHLBI NIH HHS R24 HL123828NHLBI NIH HHS R35 HL150876NHLBI NIH HHS U01 HL100402NHLBI NIH HHS U01 HL134745NHLBI NIH HHS U01 HL134766
Abstract
Mutant KRAS is a common driver in epithelial cancers. Nevertheless, molecular changes occurring early after activation of oncogenic KRAS in epithelial cells remain poorly understood. We compared transcriptional changes at single-cell resolution after KRAS activation in four sample sets. In addition to patient samples and genetically engineered mouse models, we developed organoid systems from primary mouse and human induced pluripotent stem cell-derived lung epithelial cells to model early-stage lung adenocarcinoma. In all four settings, alveolar epithelial progenitor (AT2) cells expressing oncogenic KRAS had reduced expression of mature lineage identity genes. These findings demonstrate the utility of our in vitro organoid approaches for uncovering the early consequences of oncogenic KRAS expression. This resource provides an extensive collection of datasets and describes organoid tools to study the transcriptional and proteomic changes that distinguish normal epithelial progenitor cells from early-stage lung cancer, facilitating the search for targets for KRAS-driven tumors.
Indexed as
Induced Pluripotent Stem CellsOrganoidsAnimalsHumansLungMiceProteomicsProto-Oncogene Proteins p21(ras)KRAS protein, humanProto-Oncogene Proteins p21(ras)alveolardevelopmental programsearly-stage lung canceriPSCKRASloss of differentiationorganoidsingle-cell RNA sequencingstage IA lung adenocarcinomatumor progression
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