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 Schröder, Yu B. Y. 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, Xin Yi Choo, Carmel M. O’Brien, William A. Pastor, Di Chen, Anna L. Leichter, Haroon Naeem, Pratibha Tripathi, Partha P. Das, Alexandra Grubman, David R. Powell, Andrew L. Laslett, Laurent David, Susan K. Nilsson, Amander T. Clark, Ryan Lister, Christian M. Nefzger, Luciano G. Martelotto, Owen J. L. Rackham () and Jose M. Polo ()
Additional contact information
Xiaodong Liu: Monash University
John F. Ouyang: Duke-National University of Singapore Medical School
Fernando J. Rossello: Monash University
Jia Ping Tan: Monash University
Kathryn C. Davidson: Monash University
Daniela S. Valdes: Monash University
Jan Schröder: Monash University
Yu B. Y. Sun: Monash University
Joseph Chen: Monash University
Anja S. Knaupp: Monash University
Guizhi Sun: Monash University
Hun S. Chy: Monash University
Ziyi Huang: Monash University
Jahnvi Pflueger: The University of Western Australia
Jaber Firas: Monash University
Vincent Tano: Monash University
Sam Buckberry: The University of Western Australia
Jacob M. Paynter: Monash University
Michael R. Larcombe: Monash University
Daniel Poppe: The University of Western Australia
Xin Yi Choo: Monash University
Carmel M. O’Brien: Monash University
William A. Pastor: University of California Los Angeles
Di Chen: University of California Los Angeles
Anna L. Leichter: University of Melbourne Centre For Cancer Research, The University of Melbourne
Haroon Naeem: Monash University
Pratibha Tripathi: Monash University
Partha P. Das: Monash University
Alexandra Grubman: Monash University
David R. Powell: Monash University
Andrew L. Laslett: Monash University
Laurent David: Université de Nantes, CHU Nantes, Inserm, Centre de Recherche en Transplantation et Immunologie, UMR1064, ITUN, F-44000
Susan K. Nilsson: Monash University
Amander T. Clark: University of California Los Angeles
Ryan Lister: The University of Western Australia
Christian M. Nefzger: Monash University
Luciano G. Martelotto: University of Melbourne Centre For Cancer Research, The University of Melbourne
Owen J. L. Rackham: Duke-National University of Singapore Medical School
Jose M. Polo: Monash University

Nature, 2020, vol. 586, issue 7827, 101-107

Abstract: Abstract The 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.

Date: 2020
References: Add references at CitEc
Citations: View citations in EconPapers (9)

Downloads: (external link)
https://www.nature.com/articles/s41586-020-2734-6 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:586:y:2020:i:7827:d:10.1038_s41586-020-2734-6

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/s41586-020-2734-6

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().