Distinct Imprinting Signatures and Biased Differentiation of Human Androgenetic and Parthenogenetic Embryonic Stem Cells.,Cell Stem Cell

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Distinct Imprinting Signatures and Biased Differentiation of Human Androgenetic and Parthenogenetic Embryonic Stem Cells.
Cell Stem Cell ( IF 19.8 ) Pub Date : 2019-09-05 , DOI: 10.1016/j.stem.2019.06.013
Ido Sagi ₁ , Joao C De Pinho ₂ , Michael V Zuccaro ₃ , Chen Atzmon ₁ , Tamar Golan-Lev ₁ , Ofra Yanuka ₁ , Robert Prosser ₂ , Alexandra Sadowy ₂ , Gloria Perez ₄ , Thiago Cabral ₅ , Benjamin Glaser ₆ , Stephen H Tsang ₅ , Robin Goland ₇ , Mark V Sauer ₂ , Rogerio Lobo ₂ , Nissim Benvenisty ₁ , Dieter Egli ₈

Affiliation

The Azrieli Center for Stem Cells and Genetic Research, Department of Genetics, Silberman Institute of Life Sciences, The Hebrew University, Jerusalem 91904, Israel.
Department of Obstetrics and Gynecology and Columbia University Fertility Center, Columbia University, College of Physicians & Surgeons, New York, NY 10032, USA.
Department of Cellular Physiology and Biophysics, Columbia University, New York, NY 10032, USA.
The New York Stem Cell Foundation Research Institute, New York, NY 10019, USA.
Departments of Ophthalmology and Pathology and Cell Biology, Columbia Stem Cell Initiative, Columbia University, New York, NY 10032, USA.
Hadassah Medical Center, Department of Endocrinology, Jerusalem 9112001, Israel.
Department of Pediatrics, Naomi Berrie Diabetes Center, Columbia Stem Cell Initiative, Columbia University, New York, NY 10032, USA.
Department of Obstetrics and Gynecology and Columbia University Fertility Center, Columbia University, College of Physicians & Surgeons, New York, NY 10032, USA; Department of Pediatrics, Naomi Berrie Diabetes Center, Columbia Stem Cell Initiative, Columbia University, New York, NY 10032, USA.

Genomic imprinting is an epigenetic mechanism that results in parent-of-origin monoallelic expression of specific genes, which precludes uniparental development and underlies various diseases. Here, we explored molecular and developmental aspects of imprinting in humans by generating exclusively paternal human androgenetic embryonic stem cells (aESCs) and comparing them with exclusively maternal parthenogenetic ESCs (pESCs) and bi-parental ESCs, establishing a pluripotent cell system of distinct parental backgrounds. Analyzing the transcriptomes and methylomes of human aESCs, pESCs, and bi-parental ESCs enabled the characterization of regulatory relations at known imprinted regions and uncovered imprinted gene candidates within and outside known imprinted regions. Investigating the consequences of uniparental differentiation, we showed the known paternal-genome preference for placental contribution, revealed a similar bias toward liver differentiation, and implicated the involvement of the imprinted gene IGF2 in this process. Our results demonstrate the utility of parent-specific human ESCs for dissecting the role of imprinting in human development and disease.

中文翻译：

人类雄激素和孤雌生殖胚胎干细胞的独特印迹特征和偏向分化。

基因组印记是一种表观遗传机制，可导致特定基因的起源于父本的单等位基因表达，从而阻止单亲发育并成为各种疾病的基础。在这里，我们通过产生父系人类雄激素胚胎干细胞（aESC）并将它们与母系孤雌生殖ESC（pESC）和双亲ESC进行比较，建立了具有独特父母背景的多能细胞系统，从而探索了人类印迹的分子和发育方面。分析人类aESC，pESC和双亲ESC的转录组和甲基化组，可以表征已知印迹区域和已知印迹区域内外的未发现印迹基因候选者之间的调控关系。调查单亲分化的后果，我们显示了已知的父本基因组偏爱胎盘的作用，揭示了肝脏分化的相似偏向，并暗示了印迹基因IGF2参与了这一过程。我们的结果证明了特定于父母的人类ESC在剖析印迹在人类发育和疾病中的作用的实用性。

更新日期：2019-09-30

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