Letter | Published:

Bidirectional developmental potential in reprogrammed cells with acquired pluripotency

Nature volume 505, pages 676680 (30 January 2014) | Download Citation

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Abstract

We recently discovered an unexpected phenomenon of somatic cell reprogramming into pluripotent cells by exposure to sublethal stimuli, which we call stimulus-triggered acquisition of pluripotency (STAP)1. This reprogramming does not require nuclear transfer2,3 or genetic manipulation4. Here we report that reprogrammed STAP cells, unlike embryonic stem (ES) cells, can contribute to both embryonic and placental tissues, as seen in a blastocyst injection assay. Mouse STAP cells lose the ability to contribute to the placenta as well as trophoblast marker expression on converting into ES-like stem cells by treatment with adrenocorticotropic hormone (ACTH) and leukaemia inhibitory factor (LIF). In contrast, when cultured with Fgf4, STAP cells give rise to proliferative stem cells with enhanced trophoblastic characteristics. Notably, unlike conventional trophoblast stem cells, the Fgf4-induced stem cells from STAP cells contribute to both embryonic and placental tissues in vivo and transform into ES-like cells when cultured with LIF-containing medium. Taken together, the developmental potential of STAP cells, shown by chimaera formation and in vitro cell conversion, indicates that they represent a unique state of pluripotency.

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Data deposits

RNA-seq and ChIP-seq files have been submitted to the NCBI BioSample databases under accessions SAMN02393426, SAMN02393427, SAMN02393428, SAMN02393429, SAMN02393430, SAMN02393431, SAMN02393432, SAMN02393433, SAMN02393434 and SAMN02393435.

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Acknowledgements

We thank S. Nishikawa and N. Love for discussion and M. Ohgushi, S. Kuraku, M. Eiraku, S. Ohtsuka and K. Kakiguchi for help with experimental planning, material preparation and analyses. Financial support for this research was provided by Intramural RIKEN Research Budget (H.O., T.W. and Y.S.), a Scientific Research in Priority Areas (20062015) to T.W., the Network Project for Realization of Regenerative Medicine to Y.S., and Department of Anesthesiology, Perioperative and Pain Medicine at Brigham and Women’s Hospital to C.A.V.

Author information

Affiliations

  1. Laboratory for Cellular Reprogramming, RIKEN Center for Developmental Biology, Kobe 650-0047, Japan

    • Haruko Obokata
    •  & Yukari Terashita
  2. Laboratory for Genomic Reprogramming, RIKEN Center for Developmental Biology, Kobe 650-0047, Japan

    • Haruko Obokata
    • , Mikiko Tokoro
    • , Yukari Terashita
    •  & Teruhiko Wakayama
  3. Laboratory for Tissue Engineering and Regenerative Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA

    • Haruko Obokata
    •  & Charles A. Vacanti
  4. Laboratory for Organogenesis and Neurogenesis, RIKEN Center for Developmental Biology, Kobe 650-0047, Japan

    • Yoshiki Sasai
    •  & Nozomu Takata
  5. Laboratory for Pluripotent Stem Cell Studies, RIKEN Center for Developmental Biology, Kobe 650-0047, Japan

    • Hitoshi Niwa
  6. Genome Resource and Analysis Unit, RIKEN Center for Developmental Biology, Kobe 650-0047, Japan

    • Mitsutaka Kadota
    •  & Munazah Andrabi
  7. Electron Microscopy Laboratory, RIKEN Center for Developmental Biology, Kobe 650-0047, Japan

    • Shigenobu Yonemura
  8. Faculty of Life and Environmental Sciences, University of Yamanashi, Yamanashi 400-8510, Japan

    • Teruhiko Wakayama

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Contributions

H.O. and Y.S. wrote the manuscript. H.O., Y.S., M.K., M.A., N.T., S.Y. and T.W. performed experiments, and M.T. and Y.T. assisted with H.O.’s experiments. H.O., Y.S., H.N., C.A.V. and T.W. designed the project.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Haruko Obokata or Yoshiki Sasai or Teruhiko Wakayama.

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DOI

https://doi.org/10.1038/nature12969

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