Reprogramming roadmap reveals route to human induced trophoblast stem cells

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dc.contributor.authorLiu, X.
dc.contributor.authorOuyang, J.F.
dc.contributor.authorRossello, F.J.
dc.contributor.authorTan, J.P.
dc.contributor.authorDavidson, K.C.
dc.contributor.authorValdes, D.S.
dc.contributor.authorSchröder, J.
dc.contributor.authorSun, Y.B.Y.
dc.contributor.authorChen, J.
dc.contributor.authorKnaupp, A.S.
dc.contributor.authorSun, G.
dc.contributor.authorChy, H.S.
dc.contributor.authorHuang, Z.
dc.contributor.authorPflueger, J.
dc.contributor.authorFiras, J.
dc.contributor.authorTano, V.
dc.contributor.authorBuckberry, S.
dc.contributor.authorPaynter, J.M.
dc.contributor.authorLarcombe, M.R.
dc.contributor.authorPoppe, D.
dc.contributor.authoret al.
dc.date.issued2020
dc.description.abstractThe reprogramming of human somatic cells to primed or naive induced pluripotent stem cells recapitulates the stages of early embryonic development¹⁻⁶. The molecular mechanism that underpins these reprogramming processes remains largely unexplored, which impedes our understanding and limits rational improvements to reprogramming protocols. Here, to address these issues, we reconstruct molecular reprogramming trajectories of human dermal fibroblasts using single-cell transcriptomics. This revealed that reprogramming into primed and naive pluripotency follows diverging and distinct trajectories. Moreover, genome-wide analyses of accessible chromatin showed key changes in the regulatory elements of core pluripotency genes, and orchestrated global changes in chromatin accessibility over time. Integrated analysis of these datasets revealed a role for transcription factors associated with the trophectoderm lineage, and the existence of a subpopulation of cells that enter a trophectoderm-like state during reprogramming. Furthermore, this trophectoderm-like state could be captured, which enabled the derivation of induced trophoblast stem cells. Induced trophoblast stem cells are molecularly and functionally similar to trophoblast stem cells derived from human blastocysts or first-trimester placentas7. Our results provide a high-resolution roadmap for the transcription-factor-mediated reprogramming of human somatic cells, indicate a role for the trophectoderm-lineage-specific regulatory program during this process, and facilitate the direct reprogramming of somatic cells into induced trophoblast stem cells.
dc.description.statementofresponsibilityXiaodong Liu … Jose M. Polo … et al.
dc.identifier.citationNature, 2020; 586(7827):101-[107]
dc.identifier.doi10.1038/s41586-020-2734-6
dc.identifier.issn0028-0836
dc.identifier.issn1476-4687
dc.identifier.orcidMartelotto, L.G. [0000-0002-9625-1183]
dc.identifier.orcidPolo, J.M. [0000-0002-2531-778X]
dc.identifier.urihttps://hdl.handle.net/2440/133651
dc.language.isoen
dc.publisherSpringer Nature
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1104560
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1069830
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1092280
dc.relation.granthttp://purl.org/au-research/grants/arc/FT180100674
dc.rights© The Author(s), under exclusive licence to Springer Nature Limited 2020
dc.source.urihttps://doi.org/10.1038/s41586-020-2734-6
dc.subjectCellular reprogramming
dc.subject.meshChromatin
dc.subject.meshFibroblasts
dc.subject.meshTrophoblasts
dc.subject.meshEctoderm
dc.subject.meshHumans
dc.subject.meshTranscription, Genetic
dc.subject.meshGene Expression Regulation
dc.subject.meshAdult
dc.subject.meshFemale
dc.subject.meshInduced Pluripotent Stem Cells
dc.subject.meshCellular Reprogramming
dc.titleReprogramming roadmap reveals route to human induced trophoblast stem cells
dc.typeJournal article
pubs.publication-statusPublished

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