In Vivo Generation of Lung and Thyroid Tissues from Embryonic Stem Cells Using Blastocyst Complementation
| العنوان: | In Vivo Generation of Lung and Thyroid Tissues from Embryonic Stem Cells Using Blastocyst Complementation |
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| المؤلفون: | Vladimir Ustiyan, Guolun Wang, Bingqiang Wen, Minzhe Guo, Gregory T. Kalin, Cheng-Lun Na, Yan Xu, Timothy E. Weaver, Enhong Li, Veronica Galvan, Tanya V. Kalin, Jeffrey A. Whitsett, Vladimir V. Kalinichenko |
| المصدر: | American Journal of Respiratory and Critical Care Medicine. 203:471-483 |
| بيانات النشر: | American Thoracic Society, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Pulmonary and Respiratory Medicine, Cell type, Stromal cell, business.industry, Cellular differentiation, respiratory system, Critical Care and Intensive Care Medicine, Embryonic stem cell, Cell biology, 03 medical and health sciences, 0302 clinical medicine, Directed differentiation, medicine.anatomical_structure, 030228 respiratory system, embryonic structures, medicine, 030212 general & internal medicine, Blastocyst, Progenitor cell, Induced pluripotent stem cell, business |
| الوصف: | Rationale: The regeneration and replacement of lung cells or tissues from induced pluripotent stem cell- or embryonic stem cell-derived cells represent future therapies for life-threatening pulmonary disorders but are limited by technical challenges to produce highly differentiated cells able to maintain lung function. Functional lung tissue-containing airways, alveoli, vasculature, and stroma have never been produced via directed differentiation of embryonic stem cells (ESCs) or induced pluripotent stem cells. We sought to produce all tissue components of the lung from bronchi to alveoli by embryo complementation.Objectives: To determine whether ESCs are capable of generating lung tissue in Nkx2-1-/- mouse embryos with lung agenesis.Methods: Blastocyst complementation was used to produce chimeras from normal mouse ESCs and Nkx2-1-/- embryos, which lack pulmonary tissues. Nkx2-1-/- chimeras were examined using immunostaining, transmission electronic microscopy, fluorescence-activated cell sorter analysis, and single-cell RNA sequencing.Measurements and Main Results: Although peripheral pulmonary and thyroid tissues are entirely lacking in Nkx2-1 gene-deleted embryos, pulmonary and thyroid structures in Nkx2-1-/- chimeras were restored after ESC complementation. Respiratory epithelial cell lineages in restored lungs of Nkx2-1-/- chimeras were derived almost entirely from ESCs, whereas endothelial, immune, and stromal cells were mosaic. ESC-derived cells from multiple respiratory cell lineages were highly differentiated and indistinguishable from endogenous cells based on morphology, ultrastructure, gene expression signatures, and cell surface proteins used to identify cell types by fluorescence-activated cell sorter.Conclusions: Lung and thyroid tissues were generated in vivo from ESCs by blastocyst complementation. Nkx2-1-/- chimeras can be used as "bioreactors" for in vivo differentiation and functional studies of ESC-derived progenitor cells. |
| تدمد: | 1535-4970 1073-449X |
| DOI: | 10.1164/rccm.201909-1836oc |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::32dc29f04ae8b1b679248264f320d238 https://doi.org/10.1164/rccm.201909-1836oc |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi...........32dc29f04ae8b1b679248264f320d238 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15354970 1073449X |
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| DOI: | 10.1164/rccm.201909-1836oc |