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Cell Stem Cell. 2019 Sep 5;25(3):419-432.e9. doi: 10.1016/j.stem.2019.06.013.

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

Author information

1
The Azrieli Center for Stem Cells and Genetic Research, Department of Genetics, Silberman Institute of Life Sciences, The Hebrew University, Jerusalem 91904, Israel.
2
Department of Obstetrics and Gynecology and Columbia University Fertility Center, Columbia University, College of Physicians & Surgeons, New York, NY 10032, USA.
3
Department of Cellular Physiology and Biophysics, Columbia University, New York, NY 10032, USA.
4
The New York Stem Cell Foundation Research Institute, New York, NY 10019, USA.
5
Departments of Ophthalmology and Pathology and Cell Biology, Columbia Stem Cell Initiative, Columbia University, New York, NY 10032, USA.
6
Hadassah Medical Center, Department of Endocrinology, Jerusalem 9112001, Israel.
7
Department of Pediatrics, Naomi Berrie Diabetes Center, Columbia Stem Cell Initiative, Columbia University, New York, NY 10032, USA.
8
The Azrieli Center for Stem Cells and Genetic Research, Department of Genetics, Silberman Institute of Life Sciences, The Hebrew University, Jerusalem 91904, Israel. Electronic address: nissimb@mail.huji.ac.il.
9
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. Electronic address: de2220@cumc.columbia.edu.

Abstract

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.

KEYWORDS:

IGF2; androgenesis; differentiation bias; genomic imprinting; human embryonic stem cells; human pluripotent stem cells; parental imprinting; parthenogenesis

PMID:
31491396
DOI:
10.1016/j.stem.2019.06.013

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