Differentiation of uniparental human embryonic stem cells into granulosa cells reveals a paternal contribution to gonadal development.

Autor:	Keshet G; The Azrieli Center for Stem Cells and Genetic Research, Department of Genetics, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Edmond J. Safra Campus, Givat Ram, Jerusalem, Israel. Electronic address: gal.cleitman@mail.huji.ac.il., Bar S; The Azrieli Center for Stem Cells and Genetic Research, Department of Genetics, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Edmond J. Safra Campus, Givat Ram, Jerusalem, Israel., Sarel-Gallily R; The Azrieli Center for Stem Cells and Genetic Research, Department of Genetics, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Edmond J. Safra Campus, Givat Ram, Jerusalem, Israel., Yanuka O; The Azrieli Center for Stem Cells and Genetic Research, Department of Genetics, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Edmond J. Safra Campus, Givat Ram, Jerusalem, Israel., Benvenisty N; The Azrieli Center for Stem Cells and Genetic Research, Department of Genetics, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Edmond J. Safra Campus, Givat Ram, Jerusalem, Israel. Electronic address: nissimb@mail.huji.ac.il., Eldar-Geva T; Reproductive Endocrinology and Genetics Unit, Division of Obstetrics and Gynecology, Shaare Zedek Medical Center, Jerusalem, Israel; The Hebrew University School of Medicine, Jerusalem, Israel. Electronic address: gevat@szmc.org.il.
Jazyk:	angličtina
Zdroj:	Stem cell reports [Stem Cell Reports] 2023 Apr 11; Vol. 18 (4), pp. 817-828. Date of Electronic Publication: 2023 Mar 30.
DOI:	10.1016/j.stemcr.2023.03.004
Abstrakt:	Genomic imprinting underlies the mammalian requirement for sexual reproduction. Nonetheless, the relative contribution of the two parental genomes during human development is not fully understood. Specifically, a fascinating question is whether the formation of the gonad, which holds the ability to reproduce, depends on equal contribution from both parental genomes. Here, we differentiated androgenetic and parthenogenetic human pluripotent stem cells (hPSCs) into ovarian granulosa-like cells (GLCs). We show that in contrast to biparental and androgenetic cells, parthenogenetic hPSCs present a reduced capacity to differentiate into GLCs. We further identify the paternally expressed gene IGF2 as the most upregulated imprinted gene upon differentiation. Remarkably, while IGF2 knockout androgenetic cells fail to differentiate into GLCs, the differentiation of parthenogenetic cells supplemented with IGF2 is partly rescued. Thus, our findings unravel a surprising essentiality of genes that are only expressed from the paternal genome to the development of the female reproductive system. Competing Interests: Conflict of interests N.B. is CSO of NewStem Ltd. (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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