{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T19:43:39Z","timestamp":1789155819855,"version":"build-2803163510"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2021,2,1]],"date-time":"2021-02-01T00:00:00Z","timestamp":1612137600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":["www.atsjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,2,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>The regeneration and replacement of lung cells or tissues from induced pluripotent stem cell\u2013 or embryonic stem cell\u2013derived 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\u2013containing 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To determine whether ESCs are capable of generating lung tissue in Nkx2- \u00a01\u2212\/\u2212 mouse embryos with lung agenesis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Blastocyst complementation was used to produce chimeras from normal mouse ESCs and Nkx2-1\u2212\/\u2212 embryos, which lack pulmonary tissues. Nkx2-1\u2212\/\u2212 chimeras were examined using immunostaining, transmission electronic microscopy, fluorescence-activated cell sorter analysis, and single-cell RNA sequencing.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements and Main Results<\/jats:title>\n                    <jats:p>Although peripheral pulmonary and thyroid tissues are entirely lacking in Nkx2-1 gene-deleted embryos, pulmonary and thyroid structures in Nkx2-1\u2212\/\u2212 chimeras were restored after ESC complementation. Respiratory epithelial cell lineages in restored lungs of Nkx2-1\u2212\/\u2212 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Lung and thyroid tissues were generated in vivo from ESCs by blastocyst complementation. Nkx2-1\u2212\/\u2212 chimeras can be used as \u201cbioreactors\u201d for in vivo differentiation and functional studies of ESC-derived progenitor cells.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1164\/rccm.201909-1836oc","type":"journal-article","created":{"date-parts":[[2020,9,2]],"date-time":"2020-09-02T16:25:31Z","timestamp":1599063931000},"page":"471-483","update-policy":"https:\/\/doi.org\/10.1164\/crossmarkpolicies","source":"Crossref","is-referenced-by-count":57,"title":["<i>In Vivo<\/i>\n                    Generation of Lung and Thyroid Tissues from Embryonic Stem Cells Using Blastocyst Complementation"],"prefix":"10.1093","volume":"203","author":[{"given":"Bingqiang","family":"Wen","sequence":"first","affiliation":[{"name":"Center for Lung Regenerative Medicine, Perinatal Institute"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enhong","family":"Li","sequence":"additional","affiliation":[{"name":"Center for Lung Regenerative Medicine, Perinatal 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