{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T01:16:33Z","timestamp":1792804593033,"version":"4.5.0"},"reference-count":58,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2023,8,15]],"date-time":"2023-08-15T00:00:00Z","timestamp":1692057600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Cluster of Excellence REBIRTH","award":["EXC 62\/3"],"award-info":[{"award-number":["EXC 62\/3"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Abnormalities at any stage of trophoblast development may result in pregnancy-related complications. Many of these adverse outcomes are discovered later in pregnancy, but the underlying pathomechanisms are constituted during the first trimester. Acquiring developmentally relevant material to elucidate the disease mechanisms is difficult. Human pluripotent stem cell (hPSC) technology can provide a renewable source of relevant cells. BMP4, A83-01, and PD173074 (BAP) treatment drives trophoblast commitment of hPSCs toward syncytiotrophoblast (STB), but lacks extravillous trophoblast (EVT) cells. EVTs mediate key functions during placentation, remodeling of uterine spiral arteries, and maintenance of immunological tolerance. We optimized the protocol for a more efficient generation of HLA-Gpos EVT-like trophoblasts from primed hiPSCs. Increasing the concentrations of A83-01 and PD173074, while decreasing bulk cell density resulted in an increase in HLA-G of up to 71%. Gene expression profiling supports the advancements of our treatment regarding the generation of trophoblast cells. The reported differentiation protocol will allow for an on-demand access to human trophoblast cells enriched for HLA-Gpos EVT-like cells, allowing for the elucidation of placenta-related disorders and investigating the immunological tolerance toward the fetus, overcoming the difficulties in obtaining primary EVTs without the need for a complex differentiation pathway via na\u00efve pluripotent or trophoblast stem cells.<\/jats:p>","DOI":"10.3390\/cells12162070","type":"journal-article","created":{"date-parts":[[2023,8,15]],"date-time":"2023-08-15T11:09:44Z","timestamp":1692097784000},"page":"2070","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["An Improved Protocol for Targeted Differentiation of Primed Human Induced Pluripotent Stem Cells into HLA-G-Expressing Trophoblasts to Enable the Modeling of Placenta-Related Disorders"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-5126-6020","authenticated-orcid":false,"given":"Ian O.","family":"Shum","sequence":"first","affiliation":[{"name":"Leibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), Department of Cardiothoracic, Transplantation and Vascular Surgery (HTTG), Hannover Medical School, 30625 Hannover, Germany"},{"name":"REBIRTH-Research Center for Translational and Regenerative Medicine, Hannover Medical School, 30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvia","family":"Merkert","sequence":"additional","affiliation":[{"name":"Leibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), Department of Cardiothoracic, Transplantation and Vascular Surgery (HTTG), Hannover Medical School, 30625 Hannover, Germany"},{"name":"REBIRTH-Research Center for Translational and Regenerative Medicine, Hannover Medical School, 30625 Hannover, Germany"},{"name":"Biomedical Research in Endstage and Obstructive Lung Disease (BREATH), Member of the German Center for Lung Research (DZL), Hannover Medical School, 30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Svitlana","family":"Malysheva","sequence":"additional","affiliation":[{"name":"Leibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), Department of Cardiothoracic, Transplantation and Vascular Surgery (HTTG), Hannover Medical School, 30625 Hannover, Germany"},{"name":"REBIRTH-Research Center for Translational and Regenerative Medicine, Hannover Medical School, 30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirsten","family":"Jahn","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Neurosciences, Department of Psychiatry, Social Psychiatry and Psychotherapy, Hannover Medical School, 30625 Hannover, 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Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helge","family":"Frieling","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Neurosciences, Department of Psychiatry, Social Psychiatry and Psychotherapy, Hannover Medical School, 30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7555-218X","authenticated-orcid":false,"given":"Michael","family":"Hallensleben","sequence":"additional","affiliation":[{"name":"Institute of Transfusion Medicine and Transplant Engineering, Hannover Medical School, 30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1058-4540","authenticated-orcid":false,"given":"Ulrich","family":"Martin","sequence":"additional","affiliation":[{"name":"Leibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), Department of Cardiothoracic, Transplantation and Vascular Surgery 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Sci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1093\/humupd\/dml016","article-title":"Placental-related diseases of pregnancy: Involvement of oxidative stress and implications in human evolution","volume":"12","author":"Jauniaux","year":"2006","journal-title":"Hum. Reprod. Update"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1016\/j.bpobgyn.2010.10.012","article-title":"Defective deep placentation","volume":"25","author":"Khong","year":"2011","journal-title":"Best Pract. Res. Clin. Obstet. Gynaecol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1001\/jama.2010.102","article-title":"First-trimester determination of complications of late pregnancy","volume":"303","author":"Smith","year":"2010","journal-title":"JAMA"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1546","DOI":"10.1161\/CIRCULATIONAHA.116.021793","article-title":"Congenital Heart Defects and Indices of Placental and Fetal Growth in a Nationwide Study of 924 422 Liveborn Infants","volume":"134","author":"Matthiesen","year":"2016","journal-title":"Circulation"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"942","DOI":"10.1038\/nature01417","article-title":"Extra-embryonic function of Rb is essential for embryonic development and viability","volume":"421","author":"Wu","year":"2003","journal-title":"Nature"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2455","DOI":"10.1242\/dev.022707","article-title":"Placental rescue reveals a sole requirement for c-Myc in embryonic erythroblast survival and hematopoietic stem cell function","volume":"135","author":"Dubois","year":"2008","journal-title":"Development"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1038\/nature26002","article-title":"Placentation defects are highly prevalent in embryonic lethal mouse mutants","volume":"555","author":"Fineberg","year":"2018","journal-title":"Nature"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"dev156273","DOI":"10.1242\/dev.156273","article-title":"Comparative analysis of mouse and human placentae across gestation reveals species-specific regulators of placental development","volume":"145","author":"Soncin","year":"2018","journal-title":"Development"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1016\/j.placenta.2010.08.011","article-title":"Trophoblast invasion: Assessment of cellular models using gene expression signatures","volume":"31","author":"Bilban","year":"2010","journal-title":"Placenta"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1038\/nbt761","article-title":"BMP4 initiates human embryonic stem cell differentiation to trophoblast","volume":"20","author":"Xu","year":"2002","journal-title":"Nat. Biotechnol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1038\/nbt.2239","article-title":"Isolation of primitive endoderm, mesoderm, vascular endothelial and trophoblast progenitors from human pluripotent stem cells","volume":"30","author":"Drukker","year":"2012","journal-title":"Nat. Biotechnol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"E1212","DOI":"10.1073\/pnas.1303094110","article-title":"Complete and unidirectional conversion of human embryonic stem cells to trophoblast by BMP4","volume":"110","author":"Amita","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.placenta.2017.01.121","article-title":"Generation of trophoblast-like cells from the amnion in vitro: A novel cellular model for trophoblast development","volume":"51","author":"Wei","year":"2017","journal-title":"Placenta"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1093\/molehr\/gaaa029","article-title":"Use of a human embryonic stem cell model to discover GABRP, WFDC2, VTCN1 and ACTC1 as markers of early first trimester human trophoblast","volume":"26","author":"Karvas","year":"2020","journal-title":"Mol. Hum. Reprod."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"E2598","DOI":"10.1073\/pnas.1601630113","article-title":"Comparison of syncytiotrophoblast generated from human embryonic stem cells and from term placentas","volume":"113","author":"Yabe","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"15772","DOI":"10.1073\/pnas.2000484117","article-title":"Three types of HLA-G+ extravillous trophoblasts that have distinct immune regulatory properties","volume":"117","author":"Papuchova","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/S0143-4004(80)80012-9","article-title":"Trophoblastic Invasion of Human Decidua from 8 to 18 Weeks of Pregnancy","volume":"1","author":"Pijnenborg","year":"1980","journal-title":"Placenta"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"7219","DOI":"10.1073\/pnas.1507977112","article-title":"Human HLA-G+ extravillous trophoblasts: Immune-activating cells that interact with decidual leukocytes","volume":"112","author":"Tilburgs","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"6342","DOI":"10.1038\/s41598-018-24652-0","article-title":"Pregnancy-associated diamine oxidase originates from extravillous trophoblasts and is decreased in early-onset preeclampsia","volume":"8","author":"Velicky","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"128","DOI":"10.3389\/fimmu.2015.00128","article-title":"HLA-G Orchestrates the Early Interaction of Human Trophoblasts with the Maternal Niche","volume":"6","author":"Gregori","year":"2015","journal-title":"Front. Immunol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/j.stemcr.2016.01.006","article-title":"What Is Trophoblast? A Combination of Criteria Define Human First-Trimester Trophoblast","volume":"6","author":"Lee","year":"2016","journal-title":"Stem Cell Rep."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1093\/molehr\/6.6.535","article-title":"HLA-G expression in extravillous trophoblasts is an intrinsic property of cell differentiation: A lesson learned from ectopic pregnancies","volume":"6","author":"Ariel","year":"2000","journal-title":"Mol. Hum. Reprod."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"13602","DOI":"10.1038\/ncomms13602","article-title":"Bulk cell density and Wnt\/TGFbeta signalling regulate mesendodermal patterning of human pluripotent stem cells","volume":"7","author":"Kempf","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1016\/j.stemcr.2019.06.004","article-title":"Continuous WNT Control Enables Advanced hPSC Cardiac Processing and Prognostic Surface Marker Identification in Chemically Defined Suspension Culture","volume":"13","author":"Halloin","year":"2019","journal-title":"Stem Cell Rep."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2","volume":"15","author":"Love","year":"2014","journal-title":"Genome Biol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1038\/nmeth.1593","article-title":"Chemically defined conditions for human iPSC derivation and culture","volume":"8","author":"Chen","year":"2011","journal-title":"Nat. Methods"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.stem.2017.11.004","article-title":"Derivation of Human Trophoblast Stem Cells","volume":"22","author":"Okae","year":"2018","journal-title":"Cell Stem Cell"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"eabh2169","DOI":"10.1126\/sciadv.abh2169","article-title":"A single-cell type transcriptomics map of human tissues","volume":"7","author":"Karlsson","year":"2021","journal-title":"Sci. Adv."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"eaba7721","DOI":"10.1126\/science.aba7721","article-title":"A human cell atlas of fetal gene expression","volume":"370","author":"Cao","year":"2020","journal-title":"Science"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"4862","DOI":"10.1182\/blood-2007-12-127662","article-title":"Beyond the increasing complexity of the immunomodulatory HLA-G molecule","volume":"111","author":"Carosella","year":"2008","journal-title":"Blood"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1351","DOI":"10.1093\/intimm\/11.8.1351","article-title":"HLA-G-mediated inhibition of antigen-specific cytotoxic T lymphocytes","volume":"11","author":"Riteau","year":"1999","journal-title":"Int. Immunol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"7064","DOI":"10.1073\/pnas.0401922101","article-title":"HLA-G1-expressing antigen-presenting cells induce immunosuppressive CD4+ T cells","volume":"101","author":"LeMaoult","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3936","DOI":"10.1182\/blood-2007-04-083139","article-title":"CD3+CD4low and CD3+CD8low are induced by HLA-G: Novel human peripheral blood suppressor T-cell subsets involved in transplant acceptance","volume":"110","author":"Naji","year":"2007","journal-title":"Blood"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"11520","DOI":"10.1073\/pnas.94.21.11520","article-title":"Direct evidence to support the role of HLA-G in protecting the fetus from maternal uterine natural killer cytolysis","volume":"94","author":"Goncalves","year":"1997","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"902093","DOI":"10.3389\/fimmu.2022.902093","article-title":"Biological Characteristics of HLA-G and Its Role in Solid Organ Transplantation","volume":"13","author":"Liu","year":"2022","journal-title":"Front. Immunol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"e52504","DOI":"10.7554\/eLife.52504","article-title":"Derivation of trophoblast stem cells from naive human pluripotent stem cells","volume":"9","author":"Dong","year":"2020","journal-title":"eLife"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1040","DOI":"10.1016\/j.stem.2021.02.025","article-title":"Human naive epiblast cells possess unrestricted lineage potential","volume":"28","author":"Guo","year":"2021","journal-title":"Cell Stem Cell"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2484","DOI":"10.1016\/j.stemcr.2022.09.008","article-title":"Human primed and naive PSCs are both able to differentiate into trophoblast stem cells","volume":"17","author":"Viukov","year":"2022","journal-title":"Stem Cell Rep."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"eabf4416","DOI":"10.1126\/sciadv.abf4416","article-title":"Efficient derivation of human trophoblast stem cells from primed pluripotent stem cells","volume":"7","author":"Wei","year":"2021","journal-title":"Sci. Adv."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"e96","DOI":"10.1002\/cpsc.96","article-title":"An Improved Two-Step Protocol for Trophoblast Differentiation of Human Pluripotent Stem Cells","volume":"50","author":"Horii","year":"2019","journal-title":"Curr. Protoc. Stem Cell Biol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1829","DOI":"10.1074\/mcp.M112.020503","article-title":"Targeted proteomics of the secretory pathway reveals the secretome of mouse embryonic fibroblasts and human embryonic stem cells","volume":"11","author":"Sarkar","year":"2012","journal-title":"Mol. Cell Proteom."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"108419","DOI":"10.1016\/j.celrep.2020.108419","article-title":"Induction of Human Trophoblast Stem Cells from Somatic Cells and Pluripotent Stem Cells","volume":"33","author":"Castel","year":"2020","journal-title":"Cell Rep."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1016\/j.stem.2021.03.013","article-title":"Capturing human trophoblast development with naive pluripotent stem cells in vitro","volume":"28","author":"Io","year":"2021","journal-title":"Cell Stem Cell"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/j.stemcr.2020.06.003","article-title":"Naive Human Embryonic Stem Cells Can Give Rise to Cells with a Trophoblast-like Transcriptome and Methylome","volume":"15","author":"Cinkornpumin","year":"2020","journal-title":"Stem Cell Rep."},{"key":"ref_46","first-page":"4306","article-title":"Neuregulin-1-mediated ErbB2-ErbB3 signalling protects human trophoblasts against apoptosis to preserve differentiation","volume":"128","author":"Fock","year":"2015","journal-title":"J. Cell Sci."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"dev199749","DOI":"10.1242\/dev.199749","article-title":"Characterization of primary models of human trophoblast","volume":"148","author":"Sheridan","year":"2021","journal-title":"Development"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"5877","DOI":"10.1038\/s41598-021-85230-5","article-title":"Modeling preeclampsia using human induced pluripotent stem cells","volume":"11","author":"Horii","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"4336","DOI":"10.1073\/pnas.1816150116","article-title":"Early onset preeclampsia in a model for human placental trophoblast","volume":"116","author":"Sheridan","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"3071","DOI":"10.1038\/s41467-022-30775-w","article-title":"The microRNA cluster C19MC confers differentiation potential into trophoblast lineages upon human pluripotent stem cells","volume":"13","author":"Kobayashi","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1093\/molehr\/gas013","article-title":"The expression profile of C19MC microRNAs in primary human trophoblast cells and exosomes","volume":"18","author":"Donker","year":"2012","journal-title":"Mol. Hum. Reprod."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1269","DOI":"10.1016\/j.fertnstert.2017.05.001","article-title":"Maternal allo-recognition of the fetus","volume":"107","author":"Moffett","year":"2017","journal-title":"Fertil. Steril."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"2730","DOI":"10.3389\/fimmu.2019.02730","article-title":"The Dual Role of HLA-C in Tolerance and Immunity at the Maternal-Fetal Interface","volume":"10","author":"Papuchova","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1289","DOI":"10.1016\/j.stemcr.2022.04.014","article-title":"The product of BMP-directed differentiation protocols for human primed pluripotent stem cells is placental trophoblast and not amnion","volume":"17","author":"Seetharam","year":"2022","journal-title":"Stem Cell Rep."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1007\/s00418-002-0396-0","article-title":"Invasive depth of extravillous trophoblast correlates with cellular phenotype: A comparison of intra- and extrauterine implantation sites","volume":"117","author":"Kemp","year":"2002","journal-title":"Histochem. Cell Biol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2139","DOI":"10.1172\/JCI119387","article-title":"Human cytotrophoblasts adopt a vascular phenotype as they differentiate. A strategy for successful endovascular invasion?","volume":"99","author":"Zhou","year":"1997","journal-title":"J. Clin. Investig."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/j.humpath.2011.03.012","article-title":"Sensitivity and specificity of finding of multinucleate trophoblastic giant cells in decidua in placentas from high-risk pregnancies","volume":"43","author":"Stanek","year":"2012","journal-title":"Hum. Pathol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2760","DOI":"10.1038\/s41596-022-00744-0","article-title":"Induction of human trophoblast stem cells","volume":"17","author":"Castel","year":"2022","journal-title":"Nat. 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