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Characterization of extracellular DDX4- or Ddx4-positive ovarian cells

Nature Medicine volume 21, pages 1114–1116 (2015)Cite this article

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A few groups1,2,3,4,5 have now reported that ovarian-derived stem cells (OSCs; also known as oogonial stem cells or oocyte precursor cells) have been isolated from adult mouse5 and rat4 ovaries; these cells are able to undergo meiosis after transplantation back into recipient ovaries and give rise to offspring. These cells have also been isolated from human adult ovaries, where they can give rise to oocytes after xenotransplantation2. The marker used to isolate viable cells with germ cell characteristics, DDX4 in humans or Ddx4 in mice and rats (hereafter referred to collectively as DDX4/Ddx4), is controversial because it was historically considered to be exclusively an intracellular protein distributed in the cytoplasm of germ cells. However, DDX4/Ddx4 was reported to have a C-terminal domain that is expressed extracellularly, whereas the N terminus is expressed intracellularly2,3. DDX4/Ddx4 expression was reported in freshly isolated OSCs and after propagation for 18 months (mouse) and 4 months (human) in defined cultures by immunostaining, reverse-transcription PCR (RT-PCR), and fluorescence-activated cell sorting (FACS)2. Here we further characterize the expression of DDX4/Ddx4 in mouse, rhesus macaque and human ovarian cells using a polyclonal antibody specific to DDX4 (ab13840; Abcam, generously provided by Jonathan Tilly and purchased from Abcam).

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Figure 1: Cells isolated by FACS using a DDX4-specific antibody do not express DDX4/Ddx4.

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Acknowledgements

The authors wish to acknowledge the Division of Intramural Research NHLBI Core Facilities: DNA Sequencing and Genomics Core (J. Zhu, Y. Zhang and Y. Yang), Flow Cytometry Core (P. McCoy, L. Samsel and H. Sardon), Proteomics Core (M. Gucek and S. Patel), the Animal Surgery and Resources Core (R. Clevenger, T. Hunt and J. Hawkins) and the Hematology Branch non-human primate program staff (R. Donahue and staff). We are also grateful to L. Prickett-Rice and M. Weglarz of the FACS core facility, Harvard Stem Cell Institute, and to M. Waring of Ragon Institute. This work was supported by intramural NICHD (E.F.W.) and NHLBI (E.F.W.) funds; and by grants from USAMRMC OC110262 (B.R.R.), the Vincent Memorial Research Funds (B.R.R.) and the Advanced Medical Research Foundation (B.R.R.).

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Author notes

  1. Silvia F Hernandez and Nima A Vahidi: These authors contributed equally to this work.

  2. Bo R Rueda and Erin F Wolff: These authors jointly directed this work.

Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Vincent Center for Reproductive Biology, Massachusetts General Hospital, Boston, Massachusetts, USA

    Silvia F Hernandez & Bo R Rueda

  2. Harvard Medical School, Boston, Massachusetts, USA

    Silvia F Hernandez & Bo R Rueda

  3. Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Massachusetts General Hospital, Boston, Massachusetts, USA

    Bo R Rueda

  4. Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health, Bethesda, Maryland, USA

    Nima A Vahidi, Solji Park & Erin F Wolff

  5. National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health, Bethesda, Maryland, USA

    R Patrick Weitzel, John Tisdale & Erin F Wolff

Authors
  1. Silvia F Hernandez
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  2. Nima A Vahidi
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  3. Solji Park
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  6. Bo R Rueda
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  7. Erin F Wolff
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Correspondence to Erin F Wolff.

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E.F.W. has funding from OvaScience.

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Hernandez, S., Vahidi, N., Park, S. et al. Characterization of extracellular DDX4- or Ddx4-positive ovarian cells. Nat Med 21, 1114–1116 (2015). https://doi.org/10.1038/nm.3966

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