Human Extravillous Trophoblasts Require SRC-2 for Sustained Viability, Migration, and Invasion

Defective placentation is a recognized etiology for several gestational complications that include early pregnancy loss, preeclampsia, and intrauterine growth restriction. Sustained viability, migration, and invasion are essential cellular properties for embryonic extravillous trophoblasts to execut...

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Main Authors: Vineet K. Maurya, Pooja Popli, Bryan C. Nikolai, David M. Lonard, Ramakrishna Kommagani, Bert W. O’Malley, John P. Lydon
Format: Article
Language:English
Published: MDPI AG 2025-07-01
Series:Cells
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Online Access:https://www.mdpi.com/2073-4409/14/13/1024
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author Vineet K. Maurya
Pooja Popli
Bryan C. Nikolai
David M. Lonard
Ramakrishna Kommagani
Bert W. O’Malley
John P. Lydon
author_facet Vineet K. Maurya
Pooja Popli
Bryan C. Nikolai
David M. Lonard
Ramakrishna Kommagani
Bert W. O’Malley
John P. Lydon
author_sort Vineet K. Maurya
collection DOAJ
description Defective placentation is a recognized etiology for several gestational complications that include early pregnancy loss, preeclampsia, and intrauterine growth restriction. Sustained viability, migration, and invasion are essential cellular properties for embryonic extravillous trophoblasts to execute their roles in placental development and function, while derailment of these cellular processes is linked to placental disorders. Although the cellular functions of extravillous trophoblasts are well recognized, our understanding of the pivotal molecular determinants of these functions is incomplete. Using the HTR-8/SVneo immortalized human extravillous trophoblast cell line, we report that steroid receptor coactivator-2 (SRC-2), a coregulator of transcription factor-mediated gene expression, is essential for extravillous trophoblast cell viability, motility, and invasion. Genome-scale transcriptomics identified an SRC-2-dependent transcriptome in HTR-8/SVneo cells that encodes a diverse spectrum of proteins involved in placental tissue development and function. Underscoring the utility of this transcriptomic dataset, we demonstrate that WNT family member 9A (WNT 9A) is not only regulated by SRC-2 but is also crucial for maintaining many of the above SRC-2-dependent cellular functions of human extravillous trophoblasts.
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spelling doaj-art-37288d28b9d042b4a82fe3091df3d3e42025-08-20T03:50:17ZengMDPI AGCells2073-44092025-07-011413102410.3390/cells14131024Human Extravillous Trophoblasts Require SRC-2 for Sustained Viability, Migration, and InvasionVineet K. Maurya0Pooja Popli1Bryan C. Nikolai2David M. Lonard3Ramakrishna Kommagani4Bert W. O’Malley5John P. Lydon6Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USADepartment of Pathology and Immunology, Baylor College of Medicine, Houston, TX 77030, USADepartment of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USADepartment of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USADepartment of Pathology and Immunology, Baylor College of Medicine, Houston, TX 77030, USADepartment of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USADepartment of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USADefective placentation is a recognized etiology for several gestational complications that include early pregnancy loss, preeclampsia, and intrauterine growth restriction. Sustained viability, migration, and invasion are essential cellular properties for embryonic extravillous trophoblasts to execute their roles in placental development and function, while derailment of these cellular processes is linked to placental disorders. Although the cellular functions of extravillous trophoblasts are well recognized, our understanding of the pivotal molecular determinants of these functions is incomplete. Using the HTR-8/SVneo immortalized human extravillous trophoblast cell line, we report that steroid receptor coactivator-2 (SRC-2), a coregulator of transcription factor-mediated gene expression, is essential for extravillous trophoblast cell viability, motility, and invasion. Genome-scale transcriptomics identified an SRC-2-dependent transcriptome in HTR-8/SVneo cells that encodes a diverse spectrum of proteins involved in placental tissue development and function. Underscoring the utility of this transcriptomic dataset, we demonstrate that WNT family member 9A (WNT 9A) is not only regulated by SRC-2 but is also crucial for maintaining many of the above SRC-2-dependent cellular functions of human extravillous trophoblasts.https://www.mdpi.com/2073-4409/14/13/1024steroid receptor coactivator-2 (SRC-2)human extravillous trophoblastHTR-8/SVneotranscriptomicsWNT family member 9A (WNT 9A)
spellingShingle Vineet K. Maurya
Pooja Popli
Bryan C. Nikolai
David M. Lonard
Ramakrishna Kommagani
Bert W. O’Malley
John P. Lydon
Human Extravillous Trophoblasts Require SRC-2 for Sustained Viability, Migration, and Invasion
Cells
steroid receptor coactivator-2 (SRC-2)
human extravillous trophoblast
HTR-8/SVneo
transcriptomics
WNT family member 9A (WNT 9A)
title Human Extravillous Trophoblasts Require SRC-2 for Sustained Viability, Migration, and Invasion
title_full Human Extravillous Trophoblasts Require SRC-2 for Sustained Viability, Migration, and Invasion
title_fullStr Human Extravillous Trophoblasts Require SRC-2 for Sustained Viability, Migration, and Invasion
title_full_unstemmed Human Extravillous Trophoblasts Require SRC-2 for Sustained Viability, Migration, and Invasion
title_short Human Extravillous Trophoblasts Require SRC-2 for Sustained Viability, Migration, and Invasion
title_sort human extravillous trophoblasts require src 2 for sustained viability migration and invasion
topic steroid receptor coactivator-2 (SRC-2)
human extravillous trophoblast
HTR-8/SVneo
transcriptomics
WNT family member 9A (WNT 9A)
url https://www.mdpi.com/2073-4409/14/13/1024
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