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


Journal

Stem cell reports
ISSN: 2213-6711
Titre abrégé: Stem Cell Reports
Pays: United States
ID NLM: 101611300

Informations de publication

Date de publication:
11 04 2023
Historique:
received: 13 04 2022
revised: 03 03 2023
accepted: 06 03 2023
medline: 14 4 2023
pubmed: 1 4 2023
entrez: 31 3 2023
Statut: ppublish

Résumé

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.

Identifiants

pubmed: 37001516
pii: S2213-6711(23)00087-5
doi: 10.1016/j.stemcr.2023.03.004
pmc: PMC10147827
pii:
doi:

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

817-828

Informations de copyright

Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Conflict of interests N.B. is CSO of NewStem Ltd.

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Auteurs

Gal 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.

Shiran 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.

Roni 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.

Ofra 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.

Nissim 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.

Talia 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.

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