Super-Enhancers in Placental Development and Diseases

The proliferation of trophoblast stem (TS) cells and their differentiation into multiple lineages are pivotal for placental development and functions. Various transcription factors (TFs), such as CDX2, EOMES, GATA3, TFAP2C, and TEAD4, along with their binding sites and cis-regulatory elements, have...

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Main Authors: Gracy X. Rosario, Samuel Brown, Subhradip Karmakar, Mohammad A. Karim Rumi, Nihar R. Nayak
Format: Article
Language:English
Published: MDPI AG 2025-04-01
Series:Journal of Developmental Biology
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Online Access:https://www.mdpi.com/2221-3759/13/2/11
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author Gracy X. Rosario
Samuel Brown
Subhradip Karmakar
Mohammad A. Karim Rumi
Nihar R. Nayak
author_facet Gracy X. Rosario
Samuel Brown
Subhradip Karmakar
Mohammad A. Karim Rumi
Nihar R. Nayak
author_sort Gracy X. Rosario
collection DOAJ
description The proliferation of trophoblast stem (TS) cells and their differentiation into multiple lineages are pivotal for placental development and functions. Various transcription factors (TFs), such as CDX2, EOMES, GATA3, TFAP2C, and TEAD4, along with their binding sites and cis-regulatory elements, have been studied for their roles in trophoblast cells. While previous studies have primarily focused on individual enhancer regions in trophoblast development and differentiation, recent attention has shifted towards investigating the role of super-enhancers (SEs) in different trophoblast cell lineages. SEs are clusters of regulatory elements enriched with transcriptional regulators, forming complex gene regulatory networks via differential binding patterns and the synchronized stimulation of multiple target genes. Although the exact role of SEs remains unclear, they are commonly found near master regulator genes for specific cell types and are implicated in the transcriptional regulation of tissue-specific stem cells and lineage determination. Additionally, super-enhancers play a crucial role in regulating cellular growth and differentiation in both normal development and disease pathologies. This review summarizes recent advances on SEs’ role in placental development and the pathophysiology of placental diseases, emphasizing the potential for identifying SE-driven networks in the placenta to provide valuable insights for developing therapeutic strategies to address placental dysfunctions.
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spelling doaj-art-e0afbf6a71534081a0558cfd208df3ae2025-08-20T02:20:58ZengMDPI AGJournal of Developmental Biology2221-37592025-04-011321110.3390/jdb13020011Super-Enhancers in Placental Development and DiseasesGracy X. Rosario0Samuel Brown1Subhradip Karmakar2Mohammad A. Karim Rumi3Nihar R. Nayak4Department of Obstetrics and Gynecology, University of Missouri-Kansas City, Kansas City, MO 64108, USADepartment of Obstetrics and Gynecology, University of Missouri-Kansas City, Kansas City, MO 64108, USADepartment of Biochemistry, All India Institute of Medical Sciences, New Delhi 110029, IndiaDepartment of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS 66160, USADepartment of Obstetrics and Gynecology, University of Missouri-Kansas City, Kansas City, MO 64108, USAThe proliferation of trophoblast stem (TS) cells and their differentiation into multiple lineages are pivotal for placental development and functions. Various transcription factors (TFs), such as CDX2, EOMES, GATA3, TFAP2C, and TEAD4, along with their binding sites and cis-regulatory elements, have been studied for their roles in trophoblast cells. While previous studies have primarily focused on individual enhancer regions in trophoblast development and differentiation, recent attention has shifted towards investigating the role of super-enhancers (SEs) in different trophoblast cell lineages. SEs are clusters of regulatory elements enriched with transcriptional regulators, forming complex gene regulatory networks via differential binding patterns and the synchronized stimulation of multiple target genes. Although the exact role of SEs remains unclear, they are commonly found near master regulator genes for specific cell types and are implicated in the transcriptional regulation of tissue-specific stem cells and lineage determination. Additionally, super-enhancers play a crucial role in regulating cellular growth and differentiation in both normal development and disease pathologies. This review summarizes recent advances on SEs’ role in placental development and the pathophysiology of placental diseases, emphasizing the potential for identifying SE-driven networks in the placenta to provide valuable insights for developing therapeutic strategies to address placental dysfunctions.https://www.mdpi.com/2221-3759/13/2/11super-enhancerstranscriptional regulatorstrophoblast stem cellsplacental developmentplacental diseases
spellingShingle Gracy X. Rosario
Samuel Brown
Subhradip Karmakar
Mohammad A. Karim Rumi
Nihar R. Nayak
Super-Enhancers in Placental Development and Diseases
Journal of Developmental Biology
super-enhancers
transcriptional regulators
trophoblast stem cells
placental development
placental diseases
title Super-Enhancers in Placental Development and Diseases
title_full Super-Enhancers in Placental Development and Diseases
title_fullStr Super-Enhancers in Placental Development and Diseases
title_full_unstemmed Super-Enhancers in Placental Development and Diseases
title_short Super-Enhancers in Placental Development and Diseases
title_sort super enhancers in placental development and diseases
topic super-enhancers
transcriptional regulators
trophoblast stem cells
placental development
placental diseases
url https://www.mdpi.com/2221-3759/13/2/11
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AT subhradipkarmakar superenhancersinplacentaldevelopmentanddiseases
AT mohammadakarimrumi superenhancersinplacentaldevelopmentanddiseases
AT niharrnayak superenhancersinplacentaldevelopmentanddiseases