{"id":["DOI:10.1242/dev.202778"],"title":["Transcription factor-based transdifferentiation of human embryonic to trophoblast stem cells"],"publication_date":["2024-09-01"],"authors":{"ORCID:0000-0002-9351-1226":{"id":["ORCID:0000-0002-9351-1226"],"family_name":["Balestrini"],"personal_name":["Paula A."],"affiliations":{"ROR:0220mzb33":{"organization_name":["King's College London"]}}},"AUTHTEMP:0001":{"id":["AUTHTEMP:0001"],"family_name":["Abdelbaki"],"personal_name":["Ahmed"],"affiliations":{"ROR:053g6we49":{"organization_name":["Zagazig University"]},"ROR:04tnbqb63":{"organization_name":["The Francis Crick Institute"]}},"HDBItheme":["Early"]},"ORCID:0009-0005-5450-8496":{"id":["ORCID:0009-0005-5450-8496"],"family_name":["McCarthy"],"personal_name":["Afshan"],"affiliations":{"ROR:013meh722":{"organization_name":["University of Cambridge"]}},"HDBItheme":["Early"]},"ORCID:0000-0002-3662-9578":{"id":["ORCID:0000-0002-3662-9578"],"family_name":["Devito"],"personal_name":["Liani"],"affiliations":{"ROR:013meh722":{"organization_name":["University of Cambridge"]}}},"ORCID:0000-0001-5237-3165":{"id":["ORCID:0000-0001-5237-3165"],"family_name":["Senner"],"personal_name":["Claire E."],"affiliations":{"ROR:013meh722":{"organization_name":["University of Cambridge"]}}},"AUTHTEMP:0005":{"id":["AUTHTEMP:0005"],"family_name":["Chen"],"personal_name":["Alice E."],"affiliations":{}},"ORCID:0000-0002-6238-5570":{"id":["ORCID:0000-0002-6238-5570"],"family_name":["Munusamy"],"personal_name":["Prabhakaran"],"affiliations":{"ROR:0228w5t68":{"organization_name":["KK Women's and Children's Hospital"]}}},"ORCID:0000-0003-1670-0311":{"id":["ORCID:0000-0003-1670-0311"],"family_name":["Blakeley"],"personal_name":["Paul"],"affiliations":{"ROR:02zhqgq86":{"organization_name":["University of Hong Kong"]},"ROR:04tnbqb63":{"organization_name":["The Francis Crick Institute"]}}},"ORCID:0000-0003-3510-8268":{"id":["ORCID:0000-0003-3510-8268"],"family_name":["Elder"],"personal_name":["Kay"],"affiliations":{"ROR:04qg15997":{"organization_name":["Bourn Hall Clinic"]}}},"AUTHTEMP:0003":{"id":["AUTHTEMP:0003"],"family_name":["Snell"],"personal_name":["Phil"],"affiliations":{"ROR:04qg15997":{"organization_name":["Bourn Hall Clinic"]}}},"AUTHTEMP:0004":{"id":["AUTHTEMP:0004"],"family_name":["Christie"],"personal_name":["Leila"],"affiliations":{"ROR:04qg15997":{"organization_name":["Bourn Hall Clinic"]}}},"AUTHTEMP:0006":{"id":["AUTHTEMP:0006"],"family_name":["Serhal"],"personal_name":["Paul"],"affiliations":{"ROR:05yqeks58":{"organization_name":["The Centre for Reproductive & Genetic Health"]}}},"ORCID:0000-0001-6384-2764":{"id":["ORCID:0000-0001-6384-2764"],"family_name":["Odia"],"personal_name":["Rabi A."],"affiliations":{"ROR:05yqeks58":{"organization_name":["The Centre for Reproductive & Genetic Health"]}}},"ORCID:0000-0002-0008-4588":{"id":["ORCID:0000-0002-0008-4588"],"family_name":["Sangrithi"],"personal_name":["Mahesh"],"affiliations":{"ROR:02j1m6098":{"organization_name":["Duke-NUS Medical School"]},"ROR:0220mzb33":{"organization_name":["King's College London"]},"ROR:0228w5t68":{"organization_name":["KK Women's and Children's Hospital"]}}},"ORCID:0000-0003-1646-4734":{"id":["ORCID:0000-0003-1646-4734"],"family_name":["Niakan"],"personal_name":["Kathy K."],"affiliations":{"ROR:01d5qpn59":{"organization_name":["Babraham Institute"]},"ROR:013meh722":{"organization_name":["University of Cambridge"]},"ROR:05nz0zp31":{"organization_name":["Wellcome/MRC Cambridge Stem Cell Institute"]},"ROR:04tnbqb63":{"organization_name":["The Francis Crick Institute"]}},"HDBItheme":["Early"]},"ORCID:0000-0003-1085-8185":{"id":["ORCID:0000-0003-1085-8185"],"family_name":["Fogarty"],"personal_name":["Norah M. E."],"affiliations":{"ROR:0220mzb33":{"organization_name":["King's College London"]},"ROR:04tnbqb63":{"organization_name":["The Francis Crick Institute"]}}}},"abstract":["During the first week of development, human embryos form a blastocyst composed of an inner cell mass and trophectoderm (TE) cells, the latter of which are progenitors of placental trophoblast. Here, we investigated the expression of transcripts in the human TE from early to late blastocyst stages. We identified enrichment of the transcription factors GATA2, GATA3, TFAP2C and KLF5 and characterised their protein expression dynamics across TE development. By inducible overexpression and mRNA transfection, we determined that these factors, together with MYC, are sufficient to establish induced trophoblast stem cells (iTSCs) from primed human embryonic stem cells. These iTSCs self-renew and recapitulate morphological characteristics, gene expression profiles, and directed differentiation potential, similar to existing human TSCs. Systematic omission of each, or combinations of factors, revealed the crucial importance of GATA2 and GATA3 for iTSC transdifferentiation. Altogether, these findings provide insights into the transcription factor network that may be operational in the human TE and broaden the methods for establishing cellular models of early human placental progenitor cells, which may be useful in the future to model placental-associated diseases."],"HDBItheme":["Early"],"datasets":{"ArrayExpress:E-MTAB-10749":{"id":["ArrayExpress:E-MTAB-10749"],"title":["RNA-seq of bulk trophectoderm microdissected from human blastocysts cultured to day 5, day 6 and day 7 post-fertilisation"],"description":["5 days after fertilisation the human embryo forms a blastocyst, comprising an outer layer of trophectoderm (TE), that gives rise to placental trophoblast cells, and the inner cell mass (ICM) which later segregates into epiblast (EPI) and primitive endoderm (PE). After implantation TE differentiates into cytotrophoblast cells (CTBs) which give rise to the multinucleated syncytiotrophoblast (STB) and invasive extravillous trophoblast cells (EVTs). A conserved molecular cascade regulates TE initiation (Gerri et al. Nature 2020), but subsequent TE development is poorly defined. To study this in greater detail we performed RNA-seq analysis of human blastocysts cultured to different stages of pre-implantation TE development: Day 5: TE appearance, Day 6: TE expansion and Day 7: TE hatching."],"tags":["sequencing"]},"ArrayExpress:E-MTAB-10748":{"id":["ArrayExpress:E-MTAB-10748"],"title":["RNA-seq of bulk induced trophoblast stem cells reprogrammed from human embryonic stem cells"],"description":["Bulk RNA-seq of stable induced trophoblast stem cells generated from mRNA reprogramming. Control samples in this dataset include H9 hESCS and established trophoblast stem cells from Okae et al. 2018."],"tags":["sequencing"]}}}