Journal article

Reprogramming roadmap reveals route to human induced trophoblast stem cells

Xiaodong Liu, John F Ouyang, Fernando J Rossello, Jia Ping Tan, Kathryn C Davidson, Daniela S Valdes, Jan Schroeder, Yu BY Sun, Joseph Chen, Anja S Knaupp, Guizhi Sun, Hun S Chy, Ziyi Huang, Jahnvi Pflueger, Jaber Firas, Vincent Tano, Sam Buckberry, Jacob M Paynter, Michael R Larcombe, Daniel Poppe Show all

Nature | Nature Publishing Group | Published : 2020

Abstract

The reprogramming of human somatic cells to primed or naive induced pluripotent stem cells recapitulates the stages of early embryonic development1,2,3,4,5,6. 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 ..

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Grants

Awarded by National Health and Medical Research Council (NHMRC)


Awarded by NHMRC


Awarded by ARC


Awarded by Singapore National Research Foundation


Funding Acknowledgements

We thank staff at Monash Flowcore Facility for providing high-quality cell sorting services and technical input; S. Wang, T. Wilson and the University of Melbourne Centre for Cancer Research (UMCCR) core for assistance with next-generation library preparation and Illumina sequencing; J. Hatwell-Humble for assistance with the mouse work; and A. Purcell for providing the HLA antibodies. We acknowledge the use of the services and facilities of Micromon, Monash Micro Imaging and Monash Histology Platforms at Monash University. This work was supported by National Health and Medical Research Council (NHMRC) project grants APP1104560 to J. M. Polo and A. L. Laslett, APP1069830 to R.L., and a Monash University strategic grant awarded to C.M.N. X.L. was supported by the Monash International Postgraduate Research Scholarship, a Monash Graduate Scholarship and the Carmela and Carmelo Ridolfo Prize in Stem Cell Research. A.S.K. was supported by an NHMRC Early Career Fellowship APP1092280. J. M. Polo and R.L. were supported by Silvia and Charles Viertel Senior Medical Research Fellowships. J. M. Polo was also supported by an ARC Future Fellowship FT180100674. R.L was supported by a Howard Hughes Medical Institute International Research Scholarship. O.J.L.R. and J.F.O. were supported by a Singapore National Research Foundation Competitive Research Programme (NRF-CRP20-2017-0002). The Australian Regenerative Medicine Institute is supported by grants from the State Government of Victoria and the Australian Government.