TY - JOUR
T1 - X-chromosome inactivation in monkey embryos and pluripotent stem cells
AU - Tachibana, Masahito
AU - Ma, Hong
AU - Sparman, Michelle L.
AU - Lee, Hyo Sang
AU - Ramsey, Cathy M.
AU - Woodward, Joy S.
AU - Sritanaudomchai, Hathaitip
AU - Masterson, Keith R.
AU - Wolff, Erin E.
AU - Jia, Yibing
AU - Mitalipov, Shoukhrat M.
N1 - Funding Information:
The authors would like to acknowledge the Division of Animal Resources, Surgery Team, Assisted Reproductive Technology & Embryonic Stem Cell Core, Endocrine Technology Core, and Molecular & Cellular Biology Core at the Oregon National Primate Research Center for providing expertise and services that contributed to this project. We are grateful to Lisa Clepper and Maidina Tuohetahuntila for their technical support. This study was supported by start up funds from the Oregon National Primate Research Center and grants from the National Institutes of Health HD057121 , HD059946 , HD063276 , EY021214 , HD018185 and RR000163 . The authors have no financial affiliation that may be perceived as biasing this work.
PY - 2012/11/15
Y1 - 2012/11/15
N2 - Inactivation of one X chromosome in female mammals (XX) compensates for the reduced dosage of X-linked gene expression in males (XY). However, the inner cell mass (ICM) of mouse preimplantation blastocysts and their in vitro counterparts, pluripotent embryonic stem cells (ESCs), initially maintain two active X chromosomes (XaXa). Random X chromosome inactivation (XCI) takes place in the ICM lineage after implantation or upon differentiation of ESCs, resulting in mosaic tissues composed of two cell types carrying either maternal or paternal active X chromosomes. While the status of XCI in human embryos and ICMs remains unknown, majority of human female ESCs show non-random XCI. We demonstrate here that rhesus monkey ESCs also display monoallelic expression and methylation of X-linked genes in agreement with non-random XCI. However, XIST and other X-linked genes were expressed from both chromosomes in isolated female monkey ICMs indicating that ex vivo pluripotent cells retain XaXa. Intriguingly, the trophectoderm (TE) in preimplantation monkey blastocysts also expressed X-linked genes from both alleles suggesting that, unlike the mouse, primate TE lineage does not support imprinted paternal XCI. Our results provide insights into the species-specific nature of XCI in the primate system and reveal fundamental epigenetic differences between in vitro and ex vivo primate pluripotent cells.
AB - Inactivation of one X chromosome in female mammals (XX) compensates for the reduced dosage of X-linked gene expression in males (XY). However, the inner cell mass (ICM) of mouse preimplantation blastocysts and their in vitro counterparts, pluripotent embryonic stem cells (ESCs), initially maintain two active X chromosomes (XaXa). Random X chromosome inactivation (XCI) takes place in the ICM lineage after implantation or upon differentiation of ESCs, resulting in mosaic tissues composed of two cell types carrying either maternal or paternal active X chromosomes. While the status of XCI in human embryos and ICMs remains unknown, majority of human female ESCs show non-random XCI. We demonstrate here that rhesus monkey ESCs also display monoallelic expression and methylation of X-linked genes in agreement with non-random XCI. However, XIST and other X-linked genes were expressed from both chromosomes in isolated female monkey ICMs indicating that ex vivo pluripotent cells retain XaXa. Intriguingly, the trophectoderm (TE) in preimplantation monkey blastocysts also expressed X-linked genes from both alleles suggesting that, unlike the mouse, primate TE lineage does not support imprinted paternal XCI. Our results provide insights into the species-specific nature of XCI in the primate system and reveal fundamental epigenetic differences between in vitro and ex vivo primate pluripotent cells.
KW - Blastocyst
KW - Embryonic stem cells
KW - Inner cell mass
KW - Primates
KW - X-inactivation
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U2 - 10.1016/j.ydbio.2012.08.009
DO - 10.1016/j.ydbio.2012.08.009
M3 - Article
C2 - 22935618
AN - SCOPUS:84867139621
SN - 0012-1606
VL - 371
SP - 146
EP - 155
JO - Developmental Biology
JF - Developmental Biology
IS - 2
ER -