Pluripotency genes overexpressed in primate embryonic stem cells are localized on homologues of human chromosomes 16, 17, 19, and X.
While human embryonic stem cells (hESCs) are predisposed toward chromosomal aneploidities on 12, 17, 20, and X, rendering them susceptible to transformation, the specific genes expressed are not yet known. Here, by identifying the genes overexpressed in pluripotent rhesus ESCs (nhpESCs) and comparing them both to their genetically identical differentiated progeny (teratoma fibroblasts) and to genetically related differentiated parental cells (parental skin fibroblasts from whom gametes were used for ESC derivation), we find that some of those overexpressed genes in nhpESCs cluster preferentially on rhesus chromosomes 16, 19, 20, and X, homologues of human chromosomes 17, 19, 16, and X, respectively. Differentiated parental skin fibroblasts display gene expression profiles closer to nhpESC profiles than to teratoma cells, which are genetically identical to the pluripotent nhpESCs. Twenty over- and underexpressed pluripotency modulators, some implicated in neurogenesis, have been identified. The overexpression of some of these genes discovered using pedigreed nhpESCs derived from prime embryos generated by fertile primates, which is impossible to perform with the anonymously donated clinically discarded embryos from which hESCs are derived, independently confirms the importance of chromosome 17 and X regions in pluripotency and suggests specific candidates for targeting differentiation and transformation decisions.
Pittsburgh Development Center, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
Ahmi
A
Ben-Yehudah
Christopher S
CS
Navara
Carrie J
CJ
Redinger
Jocelyn D
JD
Mich-Basso
Carlos A
CA
Castro
Stacie
S
Oliver
Lara J
LJ
Chensny
Thomas J
TJ
Richards
Naftali
N
Kaminski
Gerald
G
Schatten
D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D002877:Chromosomes, Human; D002885:Chromosomes, Human, Pair 16; D002886:Chromosomes, Human, Pair 17; D002888:Chromosomes, Human, Pair 19; D041321:Chromosomes, Human, X; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D008253:Macaca mulatta / Q000235:genetics*; D008297:Male; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D013724:Teratoma / Q000235:genetics / Q000473:pathology