Reprogramming roadmap reveals route to human induced trophoblast stem cells.

Autor: Liu X; Department of Anatomy and Developmental Biology, Monash University, Clayton, Victoria, Australia.; Development and Stem Cells Program, Monash Biomedicine Discovery Institute, Clayton, Victoria, Australia.; Australian Regenerative Medicine Institute, Monash University, Clayton, Victoria, Australia., Ouyang JF; Program in Cardiovascular and Metabolic Disorders, Duke-National University of Singapore Medical School, Singapore, Singapore., Rossello FJ; Department of Anatomy and Developmental Biology, Monash University, Clayton, Victoria, Australia.; Development and Stem Cells Program, Monash Biomedicine Discovery Institute, Clayton, Victoria, Australia.; Australian Regenerative Medicine Institute, Monash University, Clayton, Victoria, Australia.; University of Melbourne Centre For Cancer Research, The University of Melbourne, Melbourne, Victoria, Australia., Tan JP; Department of Anatomy and Developmental Biology, Monash University, Clayton, Victoria, Australia.; Development and Stem Cells Program, Monash Biomedicine Discovery Institute, Clayton, Victoria, Australia.; Australian Regenerative Medicine Institute, Monash University, Clayton, Victoria, Australia., Davidson KC; Department of Anatomy and Developmental Biology, Monash University, Clayton, Victoria, Australia.; Development and Stem Cells Program, Monash Biomedicine Discovery Institute, Clayton, Victoria, Australia.; Australian Regenerative Medicine Institute, Monash University, Clayton, Victoria, Australia., Valdes DS; Department of Anatomy and Developmental Biology, Monash University, Clayton, Victoria, Australia.; Development and Stem Cells Program, Monash Biomedicine Discovery Institute, Clayton, Victoria, Australia.; Australian Regenerative Medicine Institute, Monash University, Clayton, Victoria, Australia., Schröder J; Department of Anatomy and Developmental Biology, Monash University, Clayton, Victoria, Australia.; Development and Stem Cells Program, Monash Biomedicine Discovery Institute, Clayton, Victoria, Australia.; Australian Regenerative Medicine Institute, Monash University, Clayton, Victoria, Australia., Sun YBY; Department of Anatomy and Developmental Biology, Monash University, Clayton, Victoria, Australia.; Development and Stem Cells Program, Monash Biomedicine Discovery Institute, Clayton, Victoria, Australia.; Australian Regenerative Medicine Institute, Monash University, Clayton, Victoria, Australia., Chen J; Department of Anatomy and Developmental Biology, Monash University, Clayton, Victoria, Australia.; Development and Stem Cells Program, Monash Biomedicine Discovery Institute, Clayton, Victoria, Australia.; Australian Regenerative Medicine Institute, Monash University, Clayton, Victoria, Australia., Knaupp AS; Department of Anatomy and Developmental Biology, Monash University, Clayton, Victoria, Australia.; Development and Stem Cells Program, Monash Biomedicine Discovery Institute, Clayton, Victoria, Australia.; Australian Regenerative Medicine Institute, Monash University, Clayton, Victoria, Australia., Sun G; Department of Anatomy and Developmental Biology, Monash University, Clayton, Victoria, Australia.; Development and Stem Cells Program, Monash Biomedicine Discovery Institute, Clayton, Victoria, Australia.; Australian Regenerative Medicine Institute, Monash University, Clayton, Victoria, Australia., Chy HS; Australian Regenerative Medicine Institute, Monash University, Clayton, Victoria, Australia.; Biomedical Manufacturing, Commonwealth Scientific and Industrial Research Organisation, Clayton, Victoria, Australia., Huang Z; Australian Regenerative Medicine Institute, Monash University, Clayton, Victoria, Australia.; Biomedical Manufacturing, Commonwealth Scientific and Industrial Research Organisation, Clayton, Victoria, Australia., Pflueger J; Australian Research Council Centre of Excellence in Plant Energy Biology, School of Molecular Sciences, The University of Western Australia, Perth, Western Australia, Australia.; The Harry Perkins Institute of Medical Research, Perth, Western Australia, Australia., Firas J; Department of Anatomy and Developmental Biology, Monash University, Clayton, Victoria, Australia.; Development and Stem Cells Program, Monash Biomedicine Discovery Institute, Clayton, Victoria, Australia.; Australian Regenerative Medicine Institute, Monash University, Clayton, Victoria, Australia., Tano V; Department of Anatomy and Developmental Biology, Monash University, Clayton, Victoria, Australia.; Development and Stem Cells Program, Monash Biomedicine Discovery Institute, Clayton, Victoria, Australia.; Australian Regenerative Medicine Institute, Monash University, Clayton, Victoria, Australia., Buckberry S; Australian Research Council Centre of Excellence in Plant Energy Biology, School of Molecular Sciences, The University of Western Australia, Perth, Western Australia, Australia.; The Harry Perkins Institute of Medical Research, Perth, Western Australia, Australia., Paynter JM; Department of Anatomy and Developmental Biology, Monash University, Clayton, Victoria, Australia.; Development and Stem Cells Program, Monash Biomedicine Discovery Institute, Clayton, Victoria, Australia.; Australian Regenerative Medicine Institute, Monash University, Clayton, Victoria, Australia., Larcombe MR; Department of Anatomy and Developmental Biology, Monash University, Clayton, Victoria, Australia.; Development and Stem Cells Program, Monash Biomedicine Discovery Institute, Clayton, Victoria, Australia.; Australian Regenerative Medicine Institute, Monash University, Clayton, Victoria, Australia., Poppe D; Australian Research Council Centre of Excellence in Plant Energy Biology, School of Molecular Sciences, The University of Western Australia, Perth, Western Australia, Australia.; The Harry Perkins Institute of Medical Research, Perth, Western Australia, Australia., Choo XY; Department of Anatomy and Developmental Biology, Monash University, Clayton, Victoria, Australia.; Development and Stem Cells Program, Monash Biomedicine Discovery Institute, Clayton, Victoria, Australia.; Australian Regenerative Medicine Institute, Monash University, Clayton, Victoria, Australia., O'Brien CM; Australian Regenerative Medicine Institute, Monash University, Clayton, Victoria, Australia.; Biomedical Manufacturing, Commonwealth Scientific and Industrial Research Organisation, Clayton, Victoria, Australia., Pastor WA; Department of Molecular Cell and Developmental Biology, University of California Los Angeles, Los Angeles, CA, USA.; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California Los Angeles, Los Angeles, CA, USA.; Department of Biochemistry, McGill University, Montreal, Quebec, Canada., Chen D; Department of Molecular Cell and Developmental Biology, University of California Los Angeles, Los Angeles, CA, USA.; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California Los Angeles, Los Angeles, CA, USA., Leichter AL; Single Cell Innovation Laboratory, University of Melbourne Centre For Cancer Research, The University of Melbourne, Melbourne, Victoria, Australia., Naeem H; Monash Bioinformatics Platform, Monash University, Melbourne, Victoria, Australia., Tripathi P; Department of Anatomy and Developmental Biology, Monash University, Clayton, Victoria, Australia.; Development and Stem Cells Program, Monash Biomedicine Discovery Institute, Clayton, Victoria, Australia., Das PP; Department of Anatomy and Developmental Biology, Monash University, Clayton, Victoria, Australia.; Development and Stem Cells Program, Monash Biomedicine Discovery Institute, Clayton, Victoria, Australia., Grubman A; Department of Anatomy and Developmental Biology, Monash University, Clayton, Victoria, Australia.; Development and Stem Cells Program, Monash Biomedicine Discovery Institute, Clayton, Victoria, Australia.; Australian Regenerative Medicine Institute, Monash University, Clayton, Victoria, Australia., Powell DR; Monash Bioinformatics Platform, Monash University, Melbourne, Victoria, Australia., Laslett AL; Australian Regenerative Medicine Institute, Monash University, Clayton, Victoria, Australia.; Biomedical Manufacturing, Commonwealth Scientific and Industrial Research Organisation, Clayton, Victoria, Australia., David L; Université de Nantes, CHU Nantes, Inserm, Centre de Recherche en Transplantation et Immunologie, UMR1064, ITUN, F-44000, Nantes, France.; Université de Nantes, CHU Nantes, Inserm, CNRS, SFR Santé, Inserm UMS016, CNRS UMS3556, F-44000, Nantes, France., Nilsson SK; Australian Regenerative Medicine Institute, Monash University, Clayton, Victoria, Australia.; Biomedical Manufacturing, Commonwealth Scientific and Industrial Research Organisation, Clayton, Victoria, Australia., Clark AT; Department of Molecular Cell and Developmental Biology, University of California Los Angeles, Los Angeles, CA, USA.; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California Los Angeles, Los Angeles, CA, USA.; Molecular Biology Institute, University of California Los Angeles, Los Angeles, CA, USA.; Jonsson Comprehensive Cancer Center, University of California Los Angeles, Los Angeles, CA, USA., Lister R; Australian Research Council Centre of Excellence in Plant Energy Biology, School of Molecular Sciences, The University of Western Australia, Perth, Western Australia, Australia.; The Harry Perkins Institute of Medical Research, Perth, Western Australia, Australia., Nefzger CM; Department of Anatomy and Developmental Biology, Monash University, Clayton, Victoria, Australia.; Development and Stem Cells Program, Monash Biomedicine Discovery Institute, Clayton, Victoria, Australia.; Australian Regenerative Medicine Institute, Monash University, Clayton, Victoria, Australia.; Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia., Martelotto LG; Single Cell Innovation Laboratory, University of Melbourne Centre For Cancer Research, The University of Melbourne, Melbourne, Victoria, Australia., Rackham OJL; Program in Cardiovascular and Metabolic Disorders, Duke-National University of Singapore Medical School, Singapore, Singapore. owen.rackham@duke-nus.edu.sg., Polo JM; Department of Anatomy and Developmental Biology, Monash University, Clayton, Victoria, Australia. jose.polo@monash.edu.; Development and Stem Cells Program, Monash Biomedicine Discovery Institute, Clayton, Victoria, Australia. jose.polo@monash.edu.; Australian Regenerative Medicine Institute, Monash University, Clayton, Victoria, Australia. jose.polo@monash.edu.
Jazyk: angličtina
Zdroj: Nature [Nature] 2020 Oct; Vol. 586 (7827), pp. 101-107. Date of Electronic Publication: 2020 Sep 16.
DOI: 10.1038/s41586-020-2734-6
Abstrakt: The reprogramming of human somatic cells to primed or naive induced pluripotent stem cells recapitulates the stages of early embryonic development 1-6 . 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 placentas 7 . 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.
Databáze: MEDLINE
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