Epigenetic Reprogramming by Somatic Cell Nuclear Transfer in Primates

Author:

Sparman Michelle1,Dighe Vikas1,Sritanaudomchai Hathaitip1,Ma Hong1,Ramsey Cathy1,Pedersen Darlene1,Clepper Lisa1,Nighot Prashant2,Wolf Don1,Hennebold Jon1,Mitalipov Shoukhrat134

Affiliation:

1. Division of Reproductive Sciences, Oregon National Primate Research Center, School of Medicine, Oregon Health and Science University, Beaverton, Oregon, USA

2. College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina, USA

3. Oregon Stem Cell Center, School of Medicine, Oregon Health and Science University, Beaverton, Oregon, USA

4. Department of Obstetrics and Gynecology, School of Medicine, Oregon Health and Science University, Beaverton, Oregon, USA

Abstract

Abstract We recently demonstrated that somatic cells from adult primates could be reprogrammed into a pluripotent state by somatic cell nuclear transfer. However, the low efficiency with donor cells from one monkey necessitated the need for large oocyte numbers. Here, we demonstrate nearly threefold higher blastocyst development and embryonic stem (ES) cell derivation rates with different nuclear donor cells. Two ES cell lines were isolated using adult female rhesus macaque skin fibroblasts as nuclear donors and oocytes retrieved from one female, following a single controlled ovarian stimulation. In addition to routine pluripotency tests involving in vitro and in vivo differentiation into various somatic cell types, primate ES cells derived from reprogrammed somatic cells were also capable of contributing to cells expressing markers of germ cells. Moreover, imprinted gene expression, methylation, telomere length, and X-inactivation analyses were consistent with accurate and extensive epigenetic reprogramming of somatic cells by oocyte-specific factors. Disclosure of potential conflicts of interest is found at the end of this article.

Funder

Oregon National Primate Research Center and Oregon Stem Cell Center

NIH

Stem Cell Research Foundation

Publisher

Oxford University Press (OUP)

Subject

Cell Biology,Developmental Biology,Molecular Medicine

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