{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T07:42:36Z","timestamp":1788248556638,"version":"build-2803163510"},"reference-count":88,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2024,11,11]],"date-time":"2024-11-11T00:00:00Z","timestamp":1731283200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University of Missouri Research Council Award"},{"name":"Kent Tomazi Memorial Research Fund in the College of Veterinary Medicine, University of Missouri"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>In mice, the fetal brain is dependent upon the placenta for factors that guide its early development. This linkage between the two organs has given rise to the term, the placenta\u2013brain axis. A similar interrelationship between the two organs may exist in humans. We hypothesize that extracellular vesicles (EVs) released from placental trophoblast (TB) cells transport small RNA and other informational biomolecules from the placenta to the brain where their contents have pleiotropic effects. Here, EVs were isolated from the medium in which human trophoblasts (TBs) had been differentiated in vitro from induced pluripotent stem cells (iPSC) and from cultured iPSC themselves, and their small RNA content analyzed by bulk RNA-seq. EVs derived from human TB cells possess unique profiles of miRs, including hsa-miR-0149-3p, hsa-302a-5p, and many long non-coding RNAs (lncRNAs) relative to EVs isolated from parental iPSC. These miRs and their mRNA targets are enriched in neural tissue. Human neural progenitor cells (NPCs), generated from the same iPSC, were exposed to EVs from either TB or iPSC controls. Both sets of EVs were readily internalized. EVs from TB cells upregulate several transcripts in NPCs associated with forebrain formation and neurogenesis; those from control iPSC upregulated a transcriptional phenotype that resembled glial cells more closely than neurons. These results shed light on the possible workings of the placenta\u2013brain axis. Understanding how the contents of small RNA within TB-derived EVs affect NPCs might yield new insights, possible biomarkers, and potential treatment strategies for neurobehavioral disorders that originate in utero, such as autism spectrum disorders (ASDs).<\/jats:p>","DOI":"10.3390\/cells13221867","type":"journal-article","created":{"date-parts":[[2024,11,11]],"date-time":"2024-11-11T08:01:27Z","timestamp":1731312087000},"page":"1867","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Small and Long Non-Coding RNA Analysis for Human Trophoblast-Derived Extracellular Vesicles and Their Effect on the Transcriptome Profile of Human Neural Progenitor Cells"],"prefix":"10.3390","volume":"13","author":[{"given":"Jessica A.","family":"Kinkade","sequence":"first","affiliation":[{"name":"Biomedical Sciences, University of Missouri, Columbia, MO 65211, USA"},{"name":"Christopher S Bond Life Sciences Center, University of Missouri, Columbia, MO 65211, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pallav","family":"Singh","sequence":"additional","affiliation":[{"name":"MU Institute of Data Science and Informatics, University of Missouri, Columbia, MO 65211, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0438-5396","authenticated-orcid":false,"given":"Mohit","family":"Verma","sequence":"additional","affiliation":[{"name":"Christopher S Bond Life Sciences Center, University of Missouri, Columbia, MO 65211, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teka","family":"Khan","sequence":"additional","affiliation":[{"name":"Division of Animal Sciences, University of Missouri, Columbia, MO 65211, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6955-8449","authenticated-orcid":false,"given":"Toshihiko","family":"Ezashi","sequence":"additional","affiliation":[{"name":"Christopher S Bond Life Sciences Center, University of Missouri, Columbia, MO 65211, USA"},{"name":"Division of Animal Sciences, University of Missouri, Columbia, MO 65211, USA"},{"name":"Colorado Center for Reproductive Medicine, Lone Tree, CO 80124, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan J.","family":"Bivens","sequence":"additional","affiliation":[{"name":"Department of Genomics Technology Core Facility, University of Missouri, Columbia MO 65211, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. Michael","family":"Roberts","sequence":"additional","affiliation":[{"name":"Division of Animal Sciences, University of Missouri, Columbia, MO 65211, USA"},{"name":"Department of Biochemistry, University of Missouri, Columbia, MO 65211, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8944-4924","authenticated-orcid":false,"given":"Trupti","family":"Joshi","sequence":"additional","affiliation":[{"name":"Christopher S Bond Life Sciences Center, University of Missouri, Columbia, MO 65211, USA"},{"name":"MU Institute of Data Science and Informatics, University of Missouri, Columbia, MO 65211, USA"},{"name":"Department of Biomedical Informatics, Biostatistics and Medical Epidemiology (BBME), University of Missouri, Columbia, MO 65212, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4137-3933","authenticated-orcid":false,"given":"Cheryl S.","family":"Rosenfeld","sequence":"additional","affiliation":[{"name":"Biomedical Sciences, University of Missouri, Columbia, MO 65211, USA"},{"name":"MU Institute of Data Science and Informatics, University of Missouri, Columbia, MO 65211, USA"},{"name":"Department of Genetics Area Program, University of Missouri, Columbia, MO 65211, USA"},{"name":"Department of Thompson Center for Autism and Neurobehavioral Disorders, University of Missouri, Columbia, MO 65211, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1093\/molehr\/gap095","article-title":"Novel pathways for implantation and establishment and maintenance of pregnancy in mammals","volume":"16","author":"Bazer","year":"2009","journal-title":"Mol. Hum. Reprod."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1038\/s41422-018-0066-y","article-title":"Single-cell RNA-seq reveals the diversity of trophoblast subtypes and patterns of differentiation in the human placenta","volume":"28","author":"Liu","year":"2018","journal-title":"Cell Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1002\/jnr.24603","article-title":"The placenta-brain-axis","volume":"99","author":"Rosenfeld","year":"2020","journal-title":"J. Neurosci. Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1093\/biolre\/ioz204","article-title":"Placental serotonin signaling, pregnancy outcomes, and regulation of fetal brain development","volume":"102","author":"Rosenfeld","year":"2020","journal-title":"Biol. Reprod."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"4642","DOI":"10.1073\/pnas.1919563117","article-title":"Bisphenol A and bisphenol S disruptions of the mouse placenta and potential effects on the placenta\u2013brain axis","volume":"117","author":"Mao","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1909","DOI":"10.2217\/epi-2021-0339","article-title":"MiRNA Changes in the Mouse Placenta Due to Bisphenol a Exposure","volume":"13","author":"Mao","year":"2021","journal-title":"Epigenomics"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.placenta.2021.07.293","article-title":"Relevance of microRNAs to the regulation of the brain-placental axis in mice","volume":"112","author":"Strawn","year":"2021","journal-title":"Placenta"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13229-020-00402-w","article-title":"Evidence for the placenta-brain axis: Multi-omic kernel aggregation predicts intellectual and social impairment in children born extremely preterm","volume":"11","author":"Santos","year":"2020","journal-title":"Mol. Autism"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e46429","DOI":"10.15252\/embr.201846429","article-title":"A placental mammal-specific micro RNA cluster acts as a natural brake for sociability in mice","volume":"20","author":"Lackinger","year":"2018","journal-title":"EMBO Rep."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1186\/s12943-019-0991-5","article-title":"Exosomes: Composition, biogenesis, and mechanisms in cancer metastasis and drug resistance","volume":"18","author":"Mashouri","year":"2019","journal-title":"Mol. Cancer"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Ayala-Ram\u00edrez, P., Machuca-Acevedo, C., G\u00e1mez, T., Quijano, S., Barreto, A., Silva, J.L., Olaya-C, M., and Garc\u00eda-Robles, R. (2021). Assessment of Placental Extracellular Vesicles-Associated Fas Ligand and TNF-Related Apoptosis-Inducing Ligand in Pregnancies Complicated by Early and Late Onset Preeclampsia. Front. Physiol., 12.","DOI":"10.3389\/fphys.2021.708824"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Buca, D., Bologna, G., D\u2019amico, A., Cugini, S., Musca, F., Febbo, M., D\u2019arcangelo, D., Buca, D., Simeone, P., and Liberati, M. (2020). Extracellular Vesicles in Feto\u2013Maternal Crosstalk and Pregnancy Disorders. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21062120"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Czernek, L., and D\u00fcchler, M. (2020). Exosomes as Messengers between Mother and Fetus in Pregnancy. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21124264"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Gebara, N., Correia, Y., Wang, K., and Bussolati, B. (2021). Angiogenic Properties of Placenta-Derived Extracellular Vesicles in Normal Pregnancy and in Preeclampsia. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22105402"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1093\/jb\/mvaa137","article-title":"Impact of exosome-mediated feto-maternal interactions on pregnancy maintenance and development of obstetric complications","volume":"169","author":"Hashimoto","year":"2020","journal-title":"J. Biochem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.placenta.2021.02.012","article-title":"Extracellular vesicles and their role in gestational diabetes mellitus","volume":"113","author":"Devaskar","year":"2021","journal-title":"Placenta"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"100955","DOI":"10.1016\/j.mam.2021.100955","article-title":"The endogenous exposome of the pregnant mother: Placental extracellular vesicles and their effect on the maternal system","volume":"87","author":"Kupper","year":"2021","journal-title":"Mol. Asp. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.placenta.2020.07.001","article-title":"Placental miRNAs in feto-maternal communication mediated by extracellular vesicles","volume":"102","author":"Favaro","year":"2020","journal-title":"Placenta"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1186\/s12967-021-02999-9","article-title":"Extracellular vesicle-associated miRNAs are an adaptive response to gestational diabetes mellitus","volume":"19","author":"Nair","year":"2021","journal-title":"J. Transl. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.placenta.2020.06.011","article-title":"Extracellular vesicles as critical mediators of maternal-fetal communication during pregnancy and their potential role in maternal metabolism","volume":"98","author":"Nair","year":"2020","journal-title":"Placenta"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1007\/978-3-030-67171-6_18","article-title":"Extracellular Vesicles and Preeclampsia: Current Knowledge and Future Research Directions","volume":"Volume 97","author":"Mathivanan","year":"2021","journal-title":"Subcellular Biochemistry"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Rajaratnam, N., Ditlevsen, N.E., Sloth, J.K., B\u00e6k, R., J\u00f8rgensen, M.M., and Christiansen, O.B. (2021). Extracellular Vesicles: An Important Biomarker in Recurrent Pregnancy Loss?. J. Clin. Med., 10.","DOI":"10.3390\/jcm10122549"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Tang, Y., Groom, K., Chamley, L., and Chen, Q. (2021). Melatonin, a Potential Therapeutic Agent for Preeclampsia, Reduces the Extrusion of Toxic Extracellular Vesicles from Preeclamptic Placentae. Cells, 10.","DOI":"10.3390\/cells10081904"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Tersigni, C., Lucchetti, D., Franco, R., Colella, F., Neri, C., Crispino, L., Sgambato, A., Lanzone, A., Scambia, G., and Vatish, M. (2021). Circulating Placental Vesicles Carry HLA-DR in Pre-Eclampsia: A New Potential Marker of the Syndrome. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.717879"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"8140667","DOI":"10.1155\/2021\/8140667","article-title":"Trophoblasts Modulate the Ca2+ Oscillation and Contraction of Myometrial Smooth Muscle Cells by Small Extracellular Vesicle- (sEV-) Mediated Exporting of miR-25-3p during Premature Labor","volume":"2021","author":"Wang","year":"2021","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1093\/biolre\/ioaa152","article-title":"The promise of placental extracellular vesicles: Models and challenges for diagnosing placental dysfunction in utero","volume":"104","author":"Block","year":"2021","journal-title":"Biol. Reprod."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1161\/HYPERTENSIONAHA.123.22292","article-title":"Differential 5\u2032-tRNA Fragment Expression in Circulating Preeclampsia Syncytiotrophoblast Vesicles Drives Macrophage Inflammation","volume":"81","author":"Cooke","year":"2024","journal-title":"Hypertension"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"8728","DOI":"10.1080\/14767058.2021.2000598","article-title":"Trimester-specific associations between extracellular vesicle microRNAs and fetal growth","volume":"35","author":"Fudono","year":"2022","journal-title":"J. Matern. Neonatal Med."},{"key":"ref_29","first-page":"1","article-title":"Role of Extracellular Vesicles in Placental Inflammation and Local Immune Balance","volume":"2021","author":"Wang","year":"2021","journal-title":"Mediat. Inflamm."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"113914","DOI":"10.1016\/j.expneurol.2021.113914","article-title":"Placental mediated mechanisms of perinatal brain injury: Evolving inflammation and exosomes","volume":"347","author":"Gall","year":"2021","journal-title":"Exp. Neurol."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Go, Y.Y., Lee, C.M., Ju, W.M., Chae, S.-W., and Song, J.-J. (2021). Extracellular Vesicles (Secretomes) from Human Trophoblasts Promote the Regeneration of Skin Fibroblasts. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22136959"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1093\/biolre\/ioad146","article-title":"Extracellular vesicles from mouse trophoblast cells: Effects on neural progenitor cells and potential participants in the placenta\u2013brain axis","volume":"110","author":"Kinkade","year":"2023","journal-title":"Biol. Reprod."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Yang, P., Dai, A., Alexenko, A.P., Liu, Y., Stephens, A.J., Schulz, L.C., Schust, D.J., Roberts, R.M., and Ezashi, T. (2014). Abnormal Oxidative Stress Responses in Fibroblasts from Preeclampsia Infants. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0103110"},{"key":"ref_34","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_35","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1093\/biolre\/ioy070","article-title":"Specification of trophoblast from embryonic stem cells exposed to BMP4\u2020","volume":"99","author":"Roberts","year":"2018","journal-title":"Biol. Reprod."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00018-022-04478-w","article-title":"The role of BMP4 signaling in trophoblast emergence from pluripotency","volume":"79","author":"Roberts","year":"2022","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Roberts, R.M., Yabe, S., Yang, Y., and Ezashi, T. (2016). A Human Stem Cell Model for Creating Placental Syncytiotrophoblast, the Major Cellular Barrier that Limits Fetal Exposure to Xenobiotics. Stem Cells in Toxicology and Medicine, Wiley & Sons. [1st ed.].","DOI":"10.1002\/9781119135449.ch10"},{"key":"ref_38","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_39","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_40","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_41","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-021-90798-z","article-title":"Transcriptome analysis of MBD5-associated neurodevelopmental disorder (MAND) neural progenitor cells reveals dysregulation of autism-associated genes","volume":"11","author":"Mullegama","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"10","DOI":"10.14806\/ej.17.1.200","article-title":"Cutadapt removes adapter sequences from high-throughput sequencing reads","volume":"17","author":"Martin","year":"2011","journal-title":"EMBnet. J."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Patil, A.H., and Halushka, M.K. (2021). miRge3.0: A comprehensive microRNA and tRF sequencing analysis pipeline. NAR Genom. Bioinform., 3.","DOI":"10.1093\/nargab\/lqab068"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Love, M.I., Huber, W., and Anders, S. (2014). Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol., 15.","DOI":"10.1186\/s13059-014-0550-8"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"D211","DOI":"10.1093\/nar\/gkab808","article-title":"miRNATissueAtlas2: An update to the human miRNA tissue atlas","volume":"50","author":"Keller","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1966","DOI":"10.1093\/bioinformatics\/bty890","article-title":"TissueEnrich: Tissue-specific gene enrichment analysis","volume":"35","author":"Jain","year":"2018","journal-title":"Bioinformatics"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1093\/bioinformatics\/btp101","article-title":"ClueGO: A Cytoscape plug-in to decipher functionally grouped gene ontology and pathway annotation networks","volume":"25","author":"Bindea","year":"2009","journal-title":"Bioinformatics"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"D942","DOI":"10.1093\/nar\/gkac1071","article-title":"GENCODE: Reference annotation for the human and mouse genomes in 2023","volume":"51","author":"Frankish","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"RNAcentral Consortium (2018). RNAcentral: A hub of information for non-coding RNA sequences. Nucleic Acids Res., 47, D221\u2013D229.","DOI":"10.1093\/nar\/gky1034"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Langmead, B., Trapnell, C., Pop, M., and Salzberg, S.L. (2009). Ultrafast and memory-efficient alignment of short DNA sequences to the human genome. Genome Biol., 10.","DOI":"10.1186\/gb-2009-10-3-r25"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1093\/bioinformatics\/btt656","article-title":"featureCounts: An efficient general purpose program for assigning sequence reads to genomic features","volume":"30","author":"Liao","year":"2014","journal-title":"Bioinformatics"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"D246","DOI":"10.1093\/nar\/gks915","article-title":"LNCipedia: A database for annotated human lncRNA transcript sequences and structures","volume":"41","author":"Volders","year":"2012","journal-title":"Nucleic Acids Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"D186","DOI":"10.1093\/nar\/gkac999","article-title":"LncBook 2.0: Integrating human long non-coding RNAs with multi-omics annotations","volume":"51","author":"Li","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Li, Z., Zhang, Y., Fang, J., Xu, Z., Zhang, H., Mao, M., Chen, Y., Zhang, L., and Pian, C. (2023). NcPath: A novel platform for visualization and enrichment analysis of human non-coding RNA and KEGG signaling pathways. Bioinformatics, 39.","DOI":"10.1093\/bioinformatics\/btac812"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1093\/nar\/28.1.27","article-title":"KEGG: Kyoto Encyclopedia of Genes and Genomes","volume":"28","author":"Kanehisa","year":"2000","journal-title":"Nucleic Acids Res."},{"key":"ref_56","first-page":"1695","article-title":"The Igraph Software Package for Complex Network Research","volume":"Complex Systems","author":"Csardi","year":"2005","journal-title":"InterJournal"},{"key":"ref_57","unstructured":"R Core Team (2024). R: A Language and Environment for Statistical Computing, R Foundation for Statistical Computing."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1774","DOI":"10.12688\/f1000research.20887.2","article-title":"RCy3: Network biology using Cytoscape from within R","volume":"8","author":"Gustavsen","year":"2019","journal-title":"F1000Research"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2498","DOI":"10.1101\/gr.1239303","article-title":"Cytoscape: A software environment for integrated models of Biomolecular Interaction Networks","volume":"13","author":"Shannon","year":"2003","journal-title":"Genome Res."},{"key":"ref_60","unstructured":"Andrews, S. (2024, November 06). FastQC A Quality Control tool for High Throughput Sequence Data. Available online: http:\/\/www.bioinformatics.babraham.ac.uk\/projects\/fastqc."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"3047","DOI":"10.1093\/bioinformatics\/btw354","article-title":"MultiQC: Summarize analysis results for multiple tools and samples in a single report","volume":"32","author":"Ewels","year":"2016","journal-title":"Bioinformatics"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1038\/nmeth.3317","article-title":"HISAT: A fast spliced aligner with low memory requirements","volume":"12","author":"Kim","year":"2015","journal-title":"Nat. Methods"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"2078","DOI":"10.1093\/bioinformatics\/btp352","article-title":"The Sequence Alignment\/Map format and SAMtools","volume":"25","author":"Li","year":"2009","journal-title":"Bioinformatics"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1038\/nprot.2012.016","article-title":"Differential gene and transcript expression analysis of RNA-seq experiments with TopHat and Cufflinks","volume":"7","author":"Trapnell","year":"2012","journal-title":"Nat. Protoc."},{"key":"ref_65","unstructured":"Blighe, K., Rana, S., Turkes, E., Ostendorf, B., Grioni, A., and Lewis, M. (2018). EnhancedVolcano: Publication-ready volcano plots with enhanced colouring and labeling, R package version 1.24.0. Bioconductor."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"D447","DOI":"10.1093\/nar\/gku1003","article-title":"STRING v10: Protein\u2013protein interaction networks, integrated over the tree of life","volume":"43","author":"Szklarczyk","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Chin, C.-H., Chen, S.-H., Wu, H.-H., Ho, C.-W., Ko, M.-T., and Lin, C.-Y. (2014). cytoHubba: Identifying hub objects and sub-networks from complex interactome. BMC Syst. Biol., 8.","DOI":"10.1186\/1752-0509-8-S4-S11"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"W199","DOI":"10.1093\/nar\/gkz401","article-title":"WebGestalt 2019: Gene Set Analysis Toolkit with Revamped UIs and APIs","volume":"47","author":"Liao","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1318","DOI":"10.1126\/science.aaz1776","article-title":"The GTEx Consortium The GTEx Consortium atlas of genetic regulatory effects across human tissues","volume":"369","author":"Aguet","year":"2020","journal-title":"Science"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"4288","DOI":"10.1093\/nar\/gks042","article-title":"Differential expression analysis of multifactor RNA-Seq experiments with respect to biological variation","volume":"40","author":"McCarthy","year":"2012","journal-title":"Nucleic Acids Res."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"D127","DOI":"10.1093\/nar\/gkz757","article-title":"miRDB: An online database for prediction of functional microRNA targets","volume":"48","author":"Chen","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13059-019-1629-z","article-title":"Prediction of functional microRNA targets by integrative modeling of microRNA binding and target expression data","volume":"20","author":"Liu","year":"2019","journal-title":"Genome Biol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.placenta.2020.08.006","article-title":"Maternal oxycodone treatment causes pathophysiological changes in the mouse placenta","volume":"100","author":"Green","year":"2020","journal-title":"Placenta"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"e13133","DOI":"10.14814\/phy2.13133","article-title":"Hypothalamic transcriptomic alterations in male and female California mice (Peromyscus californicus) developmentally exposed to bisphenol A or ethinyl estradiol","volume":"5","author":"Johnson","year":"2017","journal-title":"Physiol. Rep."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1152\/physiolgenomics.00103.2016","article-title":"Transcriptomic alterations in the brain of painted turtles (Chrysemys picta) developmentally exposed to bisphenol A or ethinyl estradiol","volume":"49","author":"Manshack","year":"2017","journal-title":"Physiol. Genom."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/j.placenta.2021.09.021","article-title":"Placental Changes in the serotonin transporter (Slc6a4) knockout mouse suggest a role for serotonin in controlling nutrient acquisition","volume":"115","author":"Mao","year":"2021","journal-title":"Placenta"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1152\/physiolgenomics.00098.2019","article-title":"Mice lacking uterine enhancer of zeste homolog 2 have transcriptomic changes associated with uterine epithelial proliferation","volume":"52","author":"Mesa","year":"2020","journal-title":"Physiol. Genom."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Ortega, M.T., Bivens, N.J., Jogahara, T., Kuroiwa, A., Givan, S.A., and Rosenfeld, C.S. (2019). Sexual dimorphism in brain transcriptomes of Amami spiny rats (Tokudaia osimensis): A rodent species where males lack the Y chromosome. BMC Genom., 20.","DOI":"10.1186\/s12864-019-5426-6"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"e12614","DOI":"10.1111\/gbb.12614","article-title":"Hypothalamic transcriptome of tame and aggressive silver foxes (Vulpes vulpes) identifies gene expression differences shared across brain regions","volume":"19","author":"Rosenfeld","year":"2019","journal-title":"Genes Brain Behav."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.matbio.2015.05.006","article-title":"The extracellular matrix and transforming growth factor-\u03b21: Tale of a strained relationship","volume":"47","author":"Hinz","year":"2015","journal-title":"Matrix Biol."},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Khan, T., Seetharam, A.S., Zhou, J., Bivens, N.J., Schust, D.J., Ezashi, T., Tuteja, G., and Roberts, R.M. (2021). Single Nucleus RNA Sequence (snRNAseq) Analysis of the Spectrum of Trophoblast Lineages Generated From Human Pluripotent Stem Cells in vitro. Front. Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.695248"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1016\/j.stemcr.2014.04.014","article-title":"Single-Cell Gene Expression Profiles Define Self-Renewing, Pluripotent, and Lineage Primed States of Human Pluripotent Stem Cells","volume":"2","author":"Hough","year":"2014","journal-title":"Stem Cell Rep."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1038\/ng.3192","article-title":"The landscape of long noncoding RNAs in the human transcriptome","volume":"47","author":"Iyer","year":"2015","journal-title":"Nat. Genet."},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Yunusov, D., Anderson, L., DaSilva, L.F., Wysocka, J., Ezashi, T., Roberts, R.M., and Verjovski-Almeida, S. (2016). HIPSTR and thousands of lncRNAs are heterogeneously expressed in human embryos, primordial germ cells and stable cell lines. Sci. Rep., 6.","DOI":"10.1038\/srep32753"},{"key":"ref_85","first-page":"431","article-title":"Long non-coding RNAs: A summary of their roles in placenta development and pathology","volume":"110","author":"Cheeran","year":"2023","journal-title":"Biol. Reprod."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1016\/j.placenta.2013.03.016","article-title":"Comparison of extravillous trophoblast cells derived from human embryonic stem cells and from first trimester human placentas","volume":"34","author":"Telugu","year":"2013","journal-title":"Placenta"},{"key":"ref_87","first-page":"E2337","article-title":"Heightened potency of human pluripotent stem cell lines created by transient BMP4 exposure","volume":"112","author":"Yang","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/j.conb.2020.10.017","article-title":"Behavior and lineage progression of neural progenitors in the mammalian cortex","volume":"66","author":"Lin","year":"2020","journal-title":"Curr. Opin. Neurobiol."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/13\/22\/1867\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:30:11Z","timestamp":1760113811000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/13\/22\/1867"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,11]]},"references-count":88,"journal-issue":{"issue":"22","published-online":{"date-parts":[[2024,11]]}},"alternative-id":["cells13221867"],"URL":"https:\/\/doi.org\/10.3390\/cells13221867","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,11]]}}}