{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T12:21:48Z","timestamp":1788265308115,"version":"build-2803163510"},"reference-count":96,"publisher":"The Company of Biologists","issue":"17","license":[{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.biologists.com\/user-licence-1-2\/"}],"funder":[{"DOI":"10.13039\/100009340","name":"Children's Discovery Institute","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100009340","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"crossref","award":["R35GM153439-01"],"award-info":[{"award-number":["R35GM153439-01"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Shipley Foundation"},{"DOI":"10.13039\/100012643","name":"Edward Mallinckrodt, Jr. Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100012643","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,9,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>The chemokine G-protein-coupled receptor CCR7 is expressed in extra-embryonic tissues of the early human embryo, including trophectoderm and its derivatives: cytotrophoblast, extravillous trophoblast (EVT) and syncytiotrophoblast (STB). However, its function in placentation remains understudied. Here, we have generated human embryonic stem cells harboring CCR7 deletions and differentiated them into human trophoblast stem cells (hTSC), their EVT and STB derivatives, and trophoblast organoids. We found that CCR7 mutant hTSCs exhibited delayed EVT differentiation: they retained hTSC-like characteristics, and exhibited decreased epithelial-to-mesenchymal transition and cell motility. Investigation of trophoblast organoids using single cell transcriptomics showed that CCR7 mutant organoids comprised a smaller EVT, but a larger STB population, compared to wild type. Whereas CCR7 deficiency increased cell fusion during STB differentiation, excess CCR7 reduced expression of fusion-associated genes. Mechanistically, we found that CCR7 limited early STB differentiation by reducing cAMP levels. Transcriptional profiling of CCR7 mutant STBs identified reduced gene expression related to the placental viral defense. Together, our studies demonstrate that CCR7 plays multiple roles in cellular decision-making during trophoblast differentiation, promoting EVT differentiation and limiting cell fusion during early STB formation.<\/jats:p>","DOI":"10.1242\/dev.204309","type":"journal-article","created":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T13:42:51Z","timestamp":1756734171000},"source":"Crossref","is-referenced-by-count":0,"title":["Manifold roles of the chemokine G-protein-coupled receptor CCR7 in differentiation of human trophoblast into extravillous and syncytiotrophoblast lineages"],"prefix":"10.1242","volume":"152","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2356-7942","authenticated-orcid":false,"given":"Eun-Ja","family":"Yoon","sequence":"first","affiliation":[{"name":"Washington University in St Louis, School of Medicine 1 Department of Developmental Biology , , St Louis, MO 63110 ,","place":["USA"]},{"name":"Center of Regenerative Medicine, Washington University in St Louis, School of Medicine 2 , St Louis, MO 63110 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariana","family":"Beltcheva","sequence":"additional","affiliation":[{"name":"Washington University in St Louis, School of Medicine 1 Department of Developmental Biology , , St Louis, MO 63110 ,","place":["USA"]},{"name":"Center of Regenerative Medicine, Washington University in St Louis, School of Medicine 2 , St Louis, MO 63110 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Syed S.","family":"Ali","sequence":"additional","affiliation":[{"name":"Washington University in St Louis, School of Medicine 1 Department of Developmental Biology , , St Louis, MO 63110 ,","place":["USA"]},{"name":"Washington University in St Louis, School of Medicine 3 Division of Nephrology , , St Louis, MO 63110 ,","place":["USA"]},{"name":"Institute for Informatics (I2), Washington University in St Louis, School of Medicine 4 , St Louis, MO 63110 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuhua","family":"Fu","sequence":"additional","affiliation":[{"name":"Washington University in St Louis, School of Medicine 1 Department of Developmental Biology , , St Louis, MO 63110 ,","place":["USA"]},{"name":"Center of Regenerative Medicine, Washington University in St Louis, School of Medicine 2 , St Louis, MO 63110 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda","family":"Yang","sequence":"additional","affiliation":[{"name":"Washington University in St Louis, School of Medicine 1 Department of Developmental Biology , , St Louis, MO 63110 ,","place":["USA"]},{"name":"Washington University in St Louis, School of Medicine 3 Division of Nephrology , , St Louis, MO 63110 ,","place":["USA"]},{"name":"Institute for Informatics (I2), Washington University in St Louis, School of Medicine 4 , St Louis, MO 63110 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5405-5715","authenticated-orcid":false,"given":"Chen","family":"Dong","sequence":"additional","affiliation":[{"name":"Washington University in St Louis, School of Medicine 1 Department of Developmental Biology , , St Louis, MO 63110 ,","place":["USA"]},{"name":"Center of Regenerative Medicine, Washington University in St Louis, School of Medicine 2 , St Louis, MO 63110 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph E.","family":"Zemke","sequence":"additional","affiliation":[{"name":"Washington University in St Louis, School of Medicine 1 Department of Developmental Biology , , St Louis, MO 63110 ,","place":["USA"]},{"name":"Center of Regenerative Medicine, Washington University in St Louis, School of Medicine 2 , St Louis, MO 63110 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rowan M.","family":"Karvas","sequence":"additional","affiliation":[{"name":"Washington University in St Louis, School of Medicine 1 Department of Developmental Biology , , St Louis, MO 63110 ,","place":["USA"]},{"name":"Center of Regenerative Medicine, Washington University in St Louis, School of Medicine 2 , St Louis, MO 63110 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chia-Teng","family":"Chang","sequence":"additional","affiliation":[{"name":"Washington University in St Louis, School of Medicine 1 Department of Developmental Biology , , St Louis, MO 63110 ,","place":["USA"]},{"name":"Center of Regenerative Medicine, Washington University in St Louis, School of Medicine 2 , St Louis, MO 63110 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura A.","family":"Fischer","sequence":"additional","affiliation":[{"name":"Washington University in St Louis, School of Medicine 1 Department of Developmental Biology , , St 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