{"id":["DOI:10.1016/j.cell.2024.08.048"],"title":["mTOR activity paces human blastocyst stage developmental progression"],"publication_date":["2024-09-26"],"authors":{"ORCID:0009-0003-0036-4701":{"id":["ORCID:0009-0003-0036-4701"],"family_name":["Iyer"],"personal_name":["Dhanur P."],"affiliations":{"ROR:03ate3e03":{"organization_name":["Max Planck Institute for Molecular Genetics"]},"ROR:046ak2485":{"organization_name":["Freie Universität Berlin"]}}},"ORCID:0000-0002-7362-1698":{"id":["ORCID:0000-0002-7362-1698"],"family_name":["Khoei"],"personal_name":["Heidar Heidari"],"affiliations":{"ROR:01zqrxf85":{"organization_name":["Institute of Molecular Biotechnology"]}}},"ORCID:0000-0002-6413-0045":{"id":["ORCID:0000-0002-6413-0045"],"family_name":["Van Der Weijden"],"personal_name":["Vera A."],"affiliations":{"ROR:03ate3e03":{"organization_name":["Max Planck Institute for Molecular Genetics"]}}},"ORCID:0000-0003-0436-3805":{"id":["ORCID:0000-0003-0436-3805"],"family_name":["Kagawa"],"personal_name":["Harunobu"],"affiliations":{"ROR:01zqrxf85":{"organization_name":["Institute of Molecular Biotechnology"]}}},"ORCID:0000-0002-5306-9138":{"id":["ORCID:0000-0002-5306-9138"],"family_name":["Pradhan"],"personal_name":["Saurabh J."],"affiliations":{"ROR:01zqrxf85":{"organization_name":["Institute of Molecular Biotechnology"]}}},"ORCID:0000-0002-8462-7171":{"id":["ORCID:0000-0002-8462-7171"],"family_name":["Novatchkova"],"personal_name":["Maria"],"affiliations":{"ROR:02c5jsm26":{"organization_name":["Research Institute of Molecular Pathology"]}}},"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:0000-0001-5173-1442":{"id":["ORCID:0000-0001-5173-1442"],"family_name":["Rayon"],"personal_name":["Teresa"],"affiliations":{"ROR:01d5qpn59":{"organization_name":["Babraham Institute"]},"ROR:04tnbqb63":{"organization_name":["The Francis Crick Institute"]}},"HDBItheme":["Neural"]},"ORCID:0000-0001-9614-1403":{"id":["ORCID:0000-0001-9614-1403"],"family_name":["Simon"],"personal_name":["Claire S."],"affiliations":{"ROR:013meh722":{"organization_name":["University of Cambridge"]}}},"AUTHTEMP:00023":{"id":["AUTHTEMP:00023"],"family_name":["Dunkel"],"personal_name":["Ilona"],"affiliations":{"ROR:03ate3e03":{"organization_name":["Max Planck Institute for Molecular Genetics"]}}},"ORCID:0000-0001-6245-6255":{"id":["ORCID:0000-0001-6245-6255"],"family_name":["Wamaitha"],"personal_name":["Sissy E."],"affiliations":{"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"]}}},"ORCID:0000-0003-1253-6868":{"id":["ORCID:0000-0003-1253-6868"],"family_name":["Schulz"],"personal_name":["Edda G."],"affiliations":{"ROR:03ate3e03":{"organization_name":["Max Planck Institute for Molecular Genetics"]}}},"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:0000-0003-1590-5964":{"id":["ORCID:0000-0003-1590-5964"],"family_name":["Rivron"],"personal_name":["Nicolas"],"affiliations":{"ROR:01zqrxf85":{"organization_name":["Institute of Molecular Biotechnology"]}}},"ORCID:0000-0002-0413-9718":{"id":["ORCID:0000-0002-0413-9718"],"family_name":["Bulut-Karslioğlu"],"personal_name":["Aydan"],"affiliations":{"ROR:03ate3e03":{"organization_name":["Max Planck Institute for Molecular Genetics"]}}}},"abstract":["Many mammals can temporally uncouple conception from parturition by pacing down their development around the blastocyst stage. In mice, this dormant state is achieved by decreasing the activity of the growth-regulating mTOR signaling pathway. It is unknown whether this ability is conserved in mammals in general and in humans in particular. Here, we show that decreasing the activity of the mTOR signaling pathway induces human pluripotent stem cells (hPSCs) and blastoids to enter a dormant state with limited proliferation, developmental progression, and capacity to attach to endometrial cells. These in vitro assays show that, similar to other species, the ability to enter dormancy is active in human cells around the blastocyst stage and is reversible at both functional and molecular levels. The pacing of human blastocyst development has potential implications for reproductive therapies. Many mammals can temporally uncouple conception from parturition by pacing down their development around the blastocyst stage. In mice, this dormant state is achieved by decreasing the activity of the growth-regulating mTOR signaling pathway. It is unknown whether this ability is conserved in mammals in general and in humans in particular. Here, we show that decreasing the activity of the mTOR signaling pathway induces human pluripotent stem cells (hPSCs) and blastoids to enter a dormant state with limited proliferation, developmental progression, and capacity to attach to endometrial cells. These in vitro assays show that, similar to other species, the ability to enter dormancy is active in human cells around the blastocyst stage and is reversible at both functional and molecular levels. The pacing of human blastocyst development has potential implications for reproductive therapies."],"HDBItheme":["Early"],"datasets":{"GEO:GSE267302":{"id":["GEO:GSE267302"],"title":["mTOR activity paces human blastocyst stage developmental progression"],"description":["Many mammals can temporally uncouple conception from parturition by pacing down their development around the blastocyst stage. In mice, this dormant state is achieved by decreasing the activity of the growth-regulating mTOR signaling pathway. It is unknown whether this ability is conserved in mammals in general and in humans in particular. Here we show that decreasing the activity of the mTOR signaling pathway induces human pluripotent stem cells (hPSCs) and blastoids to enter a dormant state with limited proliferation, developmental progression, and capacity to attach to endometrial cells. These in vitro assays show that, similar to other species, the ability to enter dormancy is active in human cells around the blastocyst stage and is reversible at both functional and molecular levels. The pacing of human blastocyst development has potential implications for reproductive therapies\nTo test the effect of mTOR inhibition on the developmental timeline and morphology of human blastoids, these were first formed and then further cultured in the presence of the mTOR inhibitor RapaLink-1 and to test whether Rapalink-1 treated blastoids are reversible, we reactivated blastoids after 3 days of Rapalink-1 treatment and further cultured them on matrigel-coated plates."],"authors":{"ORCID:0000-0002-7362-1698":{"id":["ORCID:0000-0002-7362-1698"],"family_name":["Khoei"],"personal_name":["Heidar Heidari"],"affiliations":{"ROR:01zqrxf85":{"organization_name":["Institute of Molecular Biotechnology"]}}},"ORCID:0000-0002-5306-9138":{"id":["ORCID:0000-0002-5306-9138"],"family_name":["Pradhan"],"personal_name":["Saurabh J."],"affiliations":{"ROR:01zqrxf85":{"organization_name":["Institute of Molecular Biotechnology"]}}},"ORCID:0000-0003-1590-5964":{"id":["ORCID:0000-0003-1590-5964"],"family_name":["Rivron"],"personal_name":["Nicolas"],"affiliations":{"ROR:01zqrxf85":{"organization_name":["Institute of Molecular Biotechnology"]}}}},"tags":["sequencing"]},"PRIDE:PXD029513":{"id":["PRIDE:PXD029513"],"title":["mTOR activity paces human blastocyst stage developmental progression (data set 1)"],"description":["Many mammals can temporally uncouple conception from parturition by pacing down their development around the blastocyst stage. In mice, this dormant state is achieved by decreasing the activity of the growth-regulating mTOR signaling pathway1. It is unknown whether this ability is conserved in mammals in general and in humans in particular. Here we show that decreasing the activity of the mTOR signaling pathway induces human pluripotent stem cells (hPSCs) and blastoids to enter a dormant state with limited proliferation, developmental progression, and capacity to attach to endometrial cells. These in vitro assays show that, similar to other species, the ability to enter dormancy is active in human cells around the blastocyst stage and is reversible at both functional and molecular levels. The pacing of human blastocyst development has potential implications for reproductive therapies. "],"authors":{"ORCID:0000-0002-0170-868X":{"id":["ORCID:0000-0002-0170-868X"],"family_name":["Meierhofer"],"personal_name":["David"],"affiliations":{"ROR:03ate3e03":{"organization_name":["Max Planck Institute for Molecular Genetics"]}}},"ORCID:0000-0002-0413-9718":{"id":["ORCID:0000-0002-0413-9718"],"family_name":["Bulut-Karslioğlu"],"personal_name":["Aydan"],"affiliations":{"ROR:03ate3e03":{"organization_name":["Max Planck Institute for Molecular Genetics"]}}}},"tags":["proteomics"]},"PRIDE:PXD036258":{"id":["PRIDE:PXD036258"],"title":["mTOR activity paces human blastocyst stage developmental progression (data set 2)"],"description":["Many mammals can temporally uncouple conception from parturition by pacing down their development around the blastocyst stage. In mice, this dormant state is achieved by decreasing the activity of the growth-regulating mTOR signaling pathway1. It is unknown whether this ability is conserved in mammals in general and in humans in particular. Here we show that decreasing the activity of the mTOR signaling pathway induces human pluripotent stem cells (hPSCs) and blastoids to enter a dormant state with limited proliferation, developmental progression, and capacity to attach to endometrial cells. These in vitro assays show that, similar to other species, the ability to enter dormancy is active in human cells around the blastocyst stage and is reversible at both functional and molecular levels. The pacing of human blastocyst development has potential implications for reproductive therapies. "],"authors":{"ORCID:0000-0002-0170-868X":{"id":["ORCID:0000-0002-0170-868X"],"family_name":["Meierhofer"],"personal_name":["David"],"affiliations":{"ROR:03ate3e03":{"organization_name":["Max Planck Institute for Molecular Genetics"]}}},"ORCID:0000-0002-0413-9718":{"id":["ORCID:0000-0002-0413-9718"],"family_name":["Bulut-Karslioğlu"],"personal_name":["Aydan"],"affiliations":{"ROR:03ate3e03":{"organization_name":["Max Planck Institute for Molecular Genetics"]}}}},"tags":["proteomics"]},"PRIDE:PXD052209":{"id":["PRIDE:PXD052209"],"title":["mTOR activity paces human blastocyst stage developmental progression"],"description":["Many mammals can control the timing of gestation and birth by pausing embryonic development at the blastocyst stage. It is unknown whether the capacity to pause development is conserved, in general across mammals, and more specifically in humans. Activity of the growth regulating mTOR pathway governs developmental pausing in the mouse. Here we show a stage-specific capacity to delay the progression of human development via mTOR inhibition. In this context, human blastoids and pluripotent stem cells in naïve and naïve-like, but not primed, states can be induced to enter a dormant state, which is reversible at the functional and molecular level."],"authors":{"ORCID:0000-0003-3162-3481":{"id":["ORCID:0000-0003-3162-3481"],"family_name":["Imre"],"personal_name":["Richard"],"affiliations":{"ROR:01zqrxf85":{"organization_name":["Institute of Molecular Biotechnology"]}}},"ORCID:0000-0003-1590-5964":{"id":["ORCID:0000-0003-1590-5964"],"family_name":["Rivron"],"personal_name":["Nicolas"],"affiliations":{"ROR:01zqrxf85":{"organization_name":["Institute of Molecular Biotechnology"]}}}},"tags":["proteomics"]}}}