Embryonic Stem Cells/Induced Pluripotent Stem Cell
( 3 Articles )
Epigenetic Reprogramming by Somatic Cell Nuclear Transfer in Primates
Michelle Sparman 1, Vikas Dighe 1 a, Hathaitip Sritanaudomchai 1, Hong Ma 1, Cathy Ramsey 1, Darlene Pedersen 1, Lisa Clepper 1, Prashant Nighot 4, Don Wolf 1, Jon Hennebold 1, Shoukhrat Mitalipov 1 2 3 *§
1Division of Reproductive Sciences, Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, Oregon, USA
2Oregon Stem Cell Center, Oregon Health & Science University, Beaverton, Oregon, USA
3Department of Obstetrics & Gynecology, School of Medicine, Oregon Health & Science University, Beaverton, Oregon, USA
4College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina, USA
email: Shoukhrat Mitalipov (
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*Correspondence to Shoukhrat Mitalipov, 505 N.W. 185th Avenue, Beaverton, Oregon 97006, USA
aCurrent address: National Institute for Research in Reproductive Health (ICMR), Parel Mumbai, India
Author contributions: M.S. and V.D.: conception and design, provision of study material, collection and/or assembly of data, data analysis and interpretation, manuscript writing; H.S., C.R., D.P., L.C., H.M.: provision of study material, collection and/or assembly of data, manuscript writing; P.N.: collection and/or assembly of data; D.W.: data analysis and interpretation, manuscript writing; J.H.: collection and/or assembly of data, manuscript writing; S.M.: conception and design, financial support, administrative support, collection and/or assembly of data, data analysis and interpretation, manuscript writing, final approval of manuscript.
First published online in STEM CELLS Express March 12, 2009.
§Telephone: 503-614-3709; Fax: 617-643-3170
Funded by:
- Oregon National Primate Research Center
- Oregon Stem Cell Center
- Stem Cell Research Foundation
- NIH; Grant Number: NS044330, HD18185, RR00163
Keywords
Reprogramming • Nuclear transfer • Embryonic stem cells • Primates
Abstract
We recently demonstrated that somatic cells from adult primates could be reprogrammed into a pluripotent state by somatic cell nuclear transfer (SCNT). However, the low efficiency with donor cells from one monkey necessitated the need for large oocyte numbers. Here, we demonstrate nearly three-fold 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.
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