Oncotarget

Research Papers:

The molecular characterization of porcine egg precursor cells

Te-Sha Tsai, Jacqueline Johnson, Yvonne White and Justin C. St. John _

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Oncotarget. 2017; 8:63484-63505. https://doi.org/10.18632/oncotarget.18833

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Abstract

Te-Sha Tsai1,2, Jacqueline Johnson1, Yvonne White3 and Justin C. St. John1,2

1Centre for Genetic Diseases, Hudson Institute of Medical Research, Clayton, Victoria 3168, Australia

2Centre for Genetic Diseases, Department of Molecular and Translational Science, Monash University, Clayton, Victoria 3168, Australia

3OvaScience, Inc., Waltham, MA 02451, USA

Correspondence to:

Justin C. St. John, email: justin.stjohn@hudson.org.au

Keywords: egg precursor cells, oogonial stem cells, mitochondrial DNA, mitochondrial supplementation, ageing oocyte

Received: May 05, 2017     Accepted: June 03, 2017     Published: June 28, 2017

ABSTRACT

Female-factor infertility can be caused by poor oocyte quality and depleted ovarian reserves. Egg precursor cells (EPCs), isolated from the ovarian cortex, have the potential to be used to overcome female infertility. We aimed to define the origins of EPCs by analyzing their gene expression profiles and mtDNA content using a mini-pig model. We characterized FAC-sorted DDX4+-derived porcine EPCs by performing RNA-sequencing and determined that they utilize pathways important for cell cycle and proliferation, which supports the existence of adult mitotically active oogonial cells. Expression of the pluripotent markers Sox2 and Oct4, and the primitive germ cell markers Blimp1 and Stella were not detected. However, Nanog and Ddx4 were expressed, as were the primitive germ cell markers Fragilis, c-Kit and Tert. Moreover, porcine EPCs expressed self-renewal and proliferation markers including Myc, Esrrb, Id2, Klf4, Klf5, Stat3, Fgfr1, Fgfr2 and Il6st. The presence of Zp1, Zp2, Zp3 and Nobox were not detected, indicating that porcine EPCs are not indicative of mature primordial oocytes. We performed mitochondrial DNA Next Generation Sequencing and determined that one mtDNA variant harbored by EPCs was present in oocytes, preimplantation embryos and somatic tissues over three generations in our mini-pig model indicating the potential germline origin of EPCs.


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