Efficient Generation and Transcriptomic Profiling of Human iPSC-Derived Pulmonary Neuroendocrine Cells
Summary: Expansion of pulmonary neuroendocrine cells (PNECs) is a pathological feature of many human lung diseases. Human PNECs are inherently difficult to study due to their rarity (<1% of total lung cells) and a lack of established protocols for their isolation. We used induced pluripotent stem...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2020-05-01
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| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004220302686 |
| _version_ | 1828751776792182784 |
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| author | Pooja Hor Vasu Punj Ben A. Calvert Alessandra Castaldi Alyssa J. Miller Gianni Carraro Barry R. Stripp Steven L. Brody Jason R. Spence Justin K. Ichida Amy L. Ryan (Firth) Zea Borok |
| author_facet | Pooja Hor Vasu Punj Ben A. Calvert Alessandra Castaldi Alyssa J. Miller Gianni Carraro Barry R. Stripp Steven L. Brody Jason R. Spence Justin K. Ichida Amy L. Ryan (Firth) Zea Borok |
| author_sort | Pooja Hor |
| collection | DOAJ |
| description | Summary: Expansion of pulmonary neuroendocrine cells (PNECs) is a pathological feature of many human lung diseases. Human PNECs are inherently difficult to study due to their rarity (<1% of total lung cells) and a lack of established protocols for their isolation. We used induced pluripotent stem cells (iPSCs) to generate induced PNECs (iPNECs), which express core PNEC markers, including ROBO receptors, and secrete major neuropeptides, recapitulating known functions of primary PNECs. Furthermore, we demonstrate that differentiation efficiency is increased in the presence of an air-liquid interface and inhibition of Notch signaling. Single-cell RNA sequencing (scRNA-seq) revealed a PNEC-associated gene expression profile that is concordant between iPNECs and human fetal PNECs. In addition, pseudotime analysis of scRNA-seq results suggests a basal cell origin of human iPNECs. In conclusion, our model has the potential to provide an unlimited source of human iPNECs to explore PNEC pathophysiology associated with several lung diseases. |
| first_indexed | 2024-12-10T20:58:35Z |
| format | Article |
| id | doaj.art-3b48a752bd614d27a8fbdb9eff4eef14 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-12-10T20:58:35Z |
| publishDate | 2020-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-3b48a752bd614d27a8fbdb9eff4eef142022-12-22T01:33:52ZengElsevieriScience2589-00422020-05-01235Efficient Generation and Transcriptomic Profiling of Human iPSC-Derived Pulmonary Neuroendocrine CellsPooja Hor0Vasu Punj1Ben A. Calvert2Alessandra Castaldi3Alyssa J. Miller4Gianni Carraro5Barry R. Stripp6Steven L. Brody7Jason R. Spence8Justin K. Ichida9Amy L. Ryan (Firth)10Zea Borok11Hastings Center for Pulmonary Research and Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA; Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, HMR 712, University of Southern California, Los Angeles, CA 90033, USADivision of Hematology, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USAHastings Center for Pulmonary Research and Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USAHastings Center for Pulmonary Research and Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USAProgram in Cellular and Molecular Biology, University of Michigan Medical School, Ann Arbor, MI 48109, USALung and Regenerative Medicine Institutes, Department of Medicine, Cedars Sinai Medical Center, Los Angeles, CA 90048, USALung and Regenerative Medicine Institutes, Department of Medicine, Cedars Sinai Medical Center, Los Angeles, CA 90048, USADivision of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO 63105, USAProgram in Cellular and Molecular Biology, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Department of Cell and Developmental 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, USADepartment of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, HMR 712, University of Southern California, Los Angeles, CA 90033, USA; Corresponding authorHastings Center for Pulmonary Research and Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA; Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, HMR 712, University of Southern California, Los Angeles, CA 90033, USA; Corresponding authorHastings Center for Pulmonary Research and Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA; Department of Biochemistry and Molecular Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA; Norris Comprehensive Center, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA; Corresponding authorSummary: Expansion of pulmonary neuroendocrine cells (PNECs) is a pathological feature of many human lung diseases. Human PNECs are inherently difficult to study due to their rarity (<1% of total lung cells) and a lack of established protocols for their isolation. We used induced pluripotent stem cells (iPSCs) to generate induced PNECs (iPNECs), which express core PNEC markers, including ROBO receptors, and secrete major neuropeptides, recapitulating known functions of primary PNECs. Furthermore, we demonstrate that differentiation efficiency is increased in the presence of an air-liquid interface and inhibition of Notch signaling. Single-cell RNA sequencing (scRNA-seq) revealed a PNEC-associated gene expression profile that is concordant between iPNECs and human fetal PNECs. In addition, pseudotime analysis of scRNA-seq results suggests a basal cell origin of human iPNECs. In conclusion, our model has the potential to provide an unlimited source of human iPNECs to explore PNEC pathophysiology associated with several lung diseases.http://www.sciencedirect.com/science/article/pii/S2589004220302686Cell BiologyStem Cells ResearchTranscriptomics |
| spellingShingle | Pooja Hor Vasu Punj Ben A. Calvert Alessandra Castaldi Alyssa J. Miller Gianni Carraro Barry R. Stripp Steven L. Brody Jason R. Spence Justin K. Ichida Amy L. Ryan (Firth) Zea Borok Efficient Generation and Transcriptomic Profiling of Human iPSC-Derived Pulmonary Neuroendocrine Cells iScience Cell Biology Stem Cells Research Transcriptomics |
| title | Efficient Generation and Transcriptomic Profiling of Human iPSC-Derived Pulmonary Neuroendocrine Cells |
| title_full | Efficient Generation and Transcriptomic Profiling of Human iPSC-Derived Pulmonary Neuroendocrine Cells |
| title_fullStr | Efficient Generation and Transcriptomic Profiling of Human iPSC-Derived Pulmonary Neuroendocrine Cells |
| title_full_unstemmed | Efficient Generation and Transcriptomic Profiling of Human iPSC-Derived Pulmonary Neuroendocrine Cells |
| title_short | Efficient Generation and Transcriptomic Profiling of Human iPSC-Derived Pulmonary Neuroendocrine Cells |
| title_sort | efficient generation and transcriptomic profiling of human ipsc derived pulmonary neuroendocrine cells |
| topic | Cell Biology Stem Cells Research Transcriptomics |
| url | http://www.sciencedirect.com/science/article/pii/S2589004220302686 |
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