title: Complete meiosis from human induced pluripotent stem cells.
abstract: Gamete failure-derived infertility affects millions of people worldwide; for many patients, gamete donation by unrelated donors is the only available treatment. Embryonic stem cells (ESCs) can differentiate in vitro into germ-like cells, but they are genetically unrelated to the patient. Using an in vitro protocol that aims at recapitulating development, we have achieved, for the first time, complete differentiation of human induced pluripotent stem cells (hiPSCs) to postmeiotic cells. Unlike previous reports using human ESCs, postmeiotic cells arose without the over-expression of germline related transcription factors. Moreover, we consistently obtained haploid cells from hiPSCs of different origin (keratinocytes and cord blood), produced with a different number of transcription factors, and of both genetic sexes, suggesting the independence of our approach from the epigenetic memory of the reprogrammed somatic cells. Our work brings us closer to the production of personalized human gametes in vitro.
authors.affiliation: Center for Regenerative Medicine in Barcelona, Barcelona, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Eguizabal
authors.forename: N
authors.initials: N
authors.lastname: Montserrat
authors.forename: R
authors.initials: R
authors.lastname: Vassena
authors.forename: M
authors.initials: M
authors.lastname: Barragan
authors.forename: E
authors.initials: E
authors.lastname: Garreta
authors.forename: L
authors.initials: L
authors.lastname: Garcia-Quevedo
authors.forename: F
authors.initials: F
authors.lastname: Vidal
authors.forename: A
authors.initials: A
authors.lastname: Giorgetti
authors.forename: A
authors.initials: A
authors.lastname: Veiga
authors.forename: J C
authors.initials: JC
authors.lastname: Izpisua Belmonte
mesh_terms: D015096:3-Hydroxysteroid Dehydrogenases / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing; D015703:Antigens, CD / Q000378:metabolism; D052160:Benzothiazoles / Q000494:pharmacology; D018929:Cell Culture Techniques; D018797:Cell Cycle Proteins; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D005576:Colforsin / Q000494:pharmacology; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000378:metabolism; D019175:DNA Methylation; D004268:DNA-Binding Proteins; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D015870:Gene Expression; D005786:Gene Expression Regulation; D006657:Histones / Q000378:metabolism; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D007381:Intermediate Filament Proteins / Q000378:metabolism; D007621:Karyotyping; D053605:Leukemia Inhibitory Factor / Q000494:pharmacology; D008297:Male; D008540:Meiosis; D009419:Nerve Tissue Proteins / Q000378:metabolism; D064231:Nestin; D009687:Nuclear Proteins / Q000378:metabolism; D011003:Ploidies; D011401:Promoter Regions, Genetic; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D013093:Spermatogonia / Q000166:cytology / Q000378:metabolism; D055746:Stage-Specific Embryonic Antigens / Q000378:metabolism; D014230:Triazoles / Q000494:pharmacology; D014746:Vimentin / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015703:Antigens, CD; D052160:Benzothiazoles; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D006657:Histones; D007381:Intermediate Filament Proteins; D053605:Leukemia Inhibitory Factor; C577484:NES protein, human; D009419:Nerve Tissue Proteins; D064231:Nestin; D009687:Nuclear Proteins; D011506:Proteins; C484447:STRA8 protein, human; C490060:SYCP3 protein, human; D055746:Stage-Specific Embryonic Antigens; D014230:Triazoles; D014746:Vimentin; C066584:stage-specific embryonic antigen-4; D016222:Fibroblast Growth Factor 2; D005576:Colforsin; D015096:3-Hydroxysteroid Dehydrogenases; C498288:DDX4 protein, human; D053487:DEAD-box RNA Helicases; C406527:R 115866