The role of GATA4 in mesenchymal stem cell senescence: A new frontier in regenerative medicine
The Mesenchymal Stem Cell (MSC) is a multipotent progenitor cell with known differentiation potential towards various cell lineage, making it an appealing candidate for regenerative medicine. One major contributing factor to age-related MSC dysfunction is cellular senescence, which is the hallmark o...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-03-01
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| Series: | Regenerative Therapy |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352320424002098 |
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| author | M. Arockia Babu Renuka Jyothi S Irwanjot Kaur Sachin Kumar Naveen Sharma M. Ravi Kumar Pranchal Rajput Haider Ali Gaurav Gupta Vetriselvan Subramaniyan Ling Shing Wong Vinoth Kumarasamy |
| author_facet | M. Arockia Babu Renuka Jyothi S Irwanjot Kaur Sachin Kumar Naveen Sharma M. Ravi Kumar Pranchal Rajput Haider Ali Gaurav Gupta Vetriselvan Subramaniyan Ling Shing Wong Vinoth Kumarasamy |
| author_sort | M. Arockia Babu |
| collection | DOAJ |
| description | The Mesenchymal Stem Cell (MSC) is a multipotent progenitor cell with known differentiation potential towards various cell lineage, making it an appealing candidate for regenerative medicine. One major contributing factor to age-related MSC dysfunction is cellular senescence, which is the hallmark of relatively irreversible growth arrest and changes in functional properties. GATA4, a zinc-finger transcription factor, emerges as a critical regulator in MSC biology. Originally identified as a key regulator of heart development and specification, GATA4 has since been connected to several aspects of cellular processes, including stem cell proliferation and differentiation. Accumulating evidence suggests that the involvement of GATA4-nuclear signalizing in the process of MSC senescence-related traits may contribute to age-induced alterations in MSC behavior. GATA4 emerged as the central player in MSC senescence, interacting with several signaling pathways. Studies have shown that GATA4 expression is reduced with age in MSCs, which is associated with increased expression levels of senescence markers and impaired regenerative potential. At the mechanistic level, GATA4 regulates the expression of genes involved in cell cycle regulation, DNA repair, and oxidative stress response, thereby influencing the senescence phenotype in MSCs. The findings underscore the critical function of GATA4 in MSC homeostasis and suggest a promising new target to restore stem cell function during aging and disease. A better understanding of the molecular mechanisms that underlie GATA4 mediated modulation of MSC senescence would provide an opportunity to develop new therapies to revitalize old MSCs to increase their regenerative function for therapeutic purposes in regenerative medicine. |
| format | Article |
| id | doaj-art-e86adcabcf08403ca4ff533770cb2f5d |
| institution | DOAJ |
| issn | 2352-3204 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Regenerative Therapy |
| spelling | doaj-art-e86adcabcf08403ca4ff533770cb2f5d2025-08-20T02:46:51ZengElsevierRegenerative Therapy2352-32042025-03-012821422610.1016/j.reth.2024.11.017The role of GATA4 in mesenchymal stem cell senescence: A new frontier in regenerative medicineM. Arockia Babu0Renuka Jyothi S1Irwanjot Kaur2Sachin Kumar3Naveen Sharma4M. Ravi Kumar5Pranchal Rajput6Haider Ali7Gaurav Gupta8Vetriselvan Subramaniyan9Ling Shing Wong10Vinoth Kumarasamy11Institute of Pharmaceutical Research, GLA University, Mathura, UP, IndiaDepartment of Biotechnology and Genetics, Jain (Deemed-to-be) University, Bengaluru, Karnataka, 560069, IndiaDepartment of Allied Healthcare and Sciences, Vivekananda Global University, Jaipur, Rajasthan, 303012, IndiaNIMS Institute of Pharmacy, NIMS University Rajasthan, Jaipur, IndiaChandigarh Pharmacy College, Chandigarh Group of College, Jhanjeri, Mohali, 140307, Punjab, IndiaDepartment of Chemistry, Raghu Engineering College, Visakhapatnam, Andhra Pradesh, 531162, IndiaSchool of Applied and Life Sciences, Division of Research and Innovation, Uttaranchal University, Dehradun, IndiaCentre for Global Health Research, Saveetha Medical College, Saveetha Institute of Medical and Technical Sciences, Saveetha University, IndiaCentre for Research Impact & Outcome, Chitkara College of Pharmacy, Chitkara University, Rajpura, Punjab, 140401, India; Centre of Medical and Bio-allied Health Sciences Research, Ajman University, Ajman, United Arab EmiratesDepartment of Medical Sciences, School of Medical and Life Sciences, Sunway University, MalaysiaFaculty of Health and Life Sciences, INTI International University, Nilai, 71800, MalaysiaDepartment of Parasitology and Medical Entomology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, 56000, Cheras, Kuala Lumpur, Malaysia; Corresponding author.The Mesenchymal Stem Cell (MSC) is a multipotent progenitor cell with known differentiation potential towards various cell lineage, making it an appealing candidate for regenerative medicine. One major contributing factor to age-related MSC dysfunction is cellular senescence, which is the hallmark of relatively irreversible growth arrest and changes in functional properties. GATA4, a zinc-finger transcription factor, emerges as a critical regulator in MSC biology. Originally identified as a key regulator of heart development and specification, GATA4 has since been connected to several aspects of cellular processes, including stem cell proliferation and differentiation. Accumulating evidence suggests that the involvement of GATA4-nuclear signalizing in the process of MSC senescence-related traits may contribute to age-induced alterations in MSC behavior. GATA4 emerged as the central player in MSC senescence, interacting with several signaling pathways. Studies have shown that GATA4 expression is reduced with age in MSCs, which is associated with increased expression levels of senescence markers and impaired regenerative potential. At the mechanistic level, GATA4 regulates the expression of genes involved in cell cycle regulation, DNA repair, and oxidative stress response, thereby influencing the senescence phenotype in MSCs. The findings underscore the critical function of GATA4 in MSC homeostasis and suggest a promising new target to restore stem cell function during aging and disease. A better understanding of the molecular mechanisms that underlie GATA4 mediated modulation of MSC senescence would provide an opportunity to develop new therapies to revitalize old MSCs to increase their regenerative function for therapeutic purposes in regenerative medicine.http://www.sciencedirect.com/science/article/pii/S2352320424002098GATA4Mesenchymal stem cellsStem cell agingCellular senescenceTranscription factorsOxidative stress |
| spellingShingle | M. Arockia Babu Renuka Jyothi S Irwanjot Kaur Sachin Kumar Naveen Sharma M. Ravi Kumar Pranchal Rajput Haider Ali Gaurav Gupta Vetriselvan Subramaniyan Ling Shing Wong Vinoth Kumarasamy The role of GATA4 in mesenchymal stem cell senescence: A new frontier in regenerative medicine Regenerative Therapy GATA4 Mesenchymal stem cells Stem cell aging Cellular senescence Transcription factors Oxidative stress |
| title | The role of GATA4 in mesenchymal stem cell senescence: A new frontier in regenerative medicine |
| title_full | The role of GATA4 in mesenchymal stem cell senescence: A new frontier in regenerative medicine |
| title_fullStr | The role of GATA4 in mesenchymal stem cell senescence: A new frontier in regenerative medicine |
| title_full_unstemmed | The role of GATA4 in mesenchymal stem cell senescence: A new frontier in regenerative medicine |
| title_short | The role of GATA4 in mesenchymal stem cell senescence: A new frontier in regenerative medicine |
| title_sort | role of gata4 in mesenchymal stem cell senescence a new frontier in regenerative medicine |
| topic | GATA4 Mesenchymal stem cells Stem cell aging Cellular senescence Transcription factors Oxidative stress |
| url | http://www.sciencedirect.com/science/article/pii/S2352320424002098 |
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