Pedigreed Primate Embryonic Stem Cells, Express Homogeneous Familial Gene Profiles

¹ Division of Developmental and Regenerative Medicine, Department of Obstetrics, Gynecology, and Reproductive Sciences, Pittsburgh Development Center, Magee-Womens Research Institute and Foundation
² University of Pittsburgh School of Medicine; Dorothy P. and Richard P. Simmons Center for Interstitial Lung Disease, Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania

^* To whom correspondence should be addressed. E-mail: gschatten{at}pdc.magee.edu.

	Abstract

Human embryonic stem cells [hESCs] hold great biomedical promise, but experiments comparing them produce heterogeneous results, raising concerns regarding their reliability and utility, though these variations may result from their disparate and anonymous origins. To determine whether primate ESCs have intrinsic biological limitations compared with mouse ESCs [mESCs], we examined expression profiles and pluripotency of newly established non-human primate ESC (nhpESCs). Ten pedigreed nhpESC lines, seven full-siblings (fraternal quadruplets and fraternal triplets) and nine half-siblings were derived from 41 rhesus embryos; derivation success correlated with embryo quality. Each line has been growing continuously for one year with stable diploid karyotype (except for one stable trisomy), expresses in vitro pluripotency markers and eight have already formed teratomas. Unlike the heterogeneous gene expression profiles found among hESCs, these nhpESCs display remarkably homogeneous profiles (>97%), with full-sibling lines nearly identical (>98.2%). Female nhpESCs express genes distinct from their brother lines; these sensitive analyses are enabled because of the very low background differences. Experimental comparisons among these primate ESCs may prove more reliable than currently available hESCs, since they are akin to inbred mouse strains in which genetic variables are also nearly eliminated. Finally, contrasting the biological similarities among these lines with the heterogeneous hESCs might suggest that additional, more uniform hESC lines are justified. Taken together, pedigreed primate ESCs display homogeneous and reliable expression profiles. These similarities to mouse ESCs suggest that heterogeneities found among hESCs likely result from their disparate origins rather than intrinsic biological limitations with primate embryonic stem cells.

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