Unraveling the function of TSC1-TSC2 complex: implications for stem cell fate

Abstract Background Tuberous sclerosis complex is a genetic disorder caused by mutations in the TSC1 or TSC2 genes, affecting multiple systems. These genes produce proteins that regulate mTORC1 activity, essential for cell function and metabolism. While mTOR inhibitors have advanced treatment, maint...

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Main Authors: Shuang Wang, Ruishuang Ma, Chong Gao, Yu-Nong Tian, Rong-Gui Hu, Han Zhang, Lan Li, Yue Li
Format: Article
Language:English
Published: BMC 2025-02-01
Series:Stem Cell Research & Therapy
Subjects:
Online Access:https://doi.org/10.1186/s13287-025-04170-3
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author Shuang Wang
Ruishuang Ma
Chong Gao
Yu-Nong Tian
Rong-Gui Hu
Han Zhang
Lan Li
Yue Li
author_facet Shuang Wang
Ruishuang Ma
Chong Gao
Yu-Nong Tian
Rong-Gui Hu
Han Zhang
Lan Li
Yue Li
author_sort Shuang Wang
collection DOAJ
description Abstract Background Tuberous sclerosis complex is a genetic disorder caused by mutations in the TSC1 or TSC2 genes, affecting multiple systems. These genes produce proteins that regulate mTORC1 activity, essential for cell function and metabolism. While mTOR inhibitors have advanced treatment, maintaining long-term therapeutic success is still challenging. For over 20 years, significant progress has linked TSC1 or TSC2 gene mutations in stem cells to tuberous sclerosis complex symptoms. Methods A comprehensive review was conducted using databases like Web of Science, Google Scholar, PubMed, and Science Direct, with search terms such as “tuberous sclerosis complex,” “TSC1,” “TSC2,” “stem cell,” “proliferation,” and “differentiation.” Relevant literature was thoroughly analyzed and summarized to present an updated analysis of the TSC1-TSC2 complex’s role in stem cell fate determination and its implications for tuberous sclerosis complex. Results The TSC1-TSC2 complex plays a crucial role in various stem cells, such as neural, germline, nephron progenitor, intestinal, hematopoietic, and mesenchymal stem/stromal cells, primarily through the mTOR signaling pathway. Conclusions This review aims shed light on the role of the TSC1-TSC2 complex in stem cell fate, its impact on health and disease, and potential new treatments for tuberous sclerosis complex. Graphical abstract
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series Stem Cell Research & Therapy
spelling doaj-art-2359feef6c034d76a7b1263927d648eb2025-02-09T12:15:39ZengBMCStem Cell Research & Therapy1757-65122025-02-0116111410.1186/s13287-025-04170-3Unraveling the function of TSC1-TSC2 complex: implications for stem cell fateShuang Wang0Ruishuang Ma1Chong Gao2Yu-Nong Tian3Rong-Gui Hu4Han Zhang5Lan Li6Yue Li7Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese MedicineInstitute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese MedicineSchool of Medicine, Institute of Brain and Cognitive Science, Hangzhou City UniversityInstitute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese MedicineState Key Laboratory of Brain-Machine Intelligence, Liangzhu Laboratory, School of Medicine, Zhejiang UniversityInstitute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese MedicineInstitute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese MedicineState Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of MacauAbstract Background Tuberous sclerosis complex is a genetic disorder caused by mutations in the TSC1 or TSC2 genes, affecting multiple systems. These genes produce proteins that regulate mTORC1 activity, essential for cell function and metabolism. While mTOR inhibitors have advanced treatment, maintaining long-term therapeutic success is still challenging. For over 20 years, significant progress has linked TSC1 or TSC2 gene mutations in stem cells to tuberous sclerosis complex symptoms. Methods A comprehensive review was conducted using databases like Web of Science, Google Scholar, PubMed, and Science Direct, with search terms such as “tuberous sclerosis complex,” “TSC1,” “TSC2,” “stem cell,” “proliferation,” and “differentiation.” Relevant literature was thoroughly analyzed and summarized to present an updated analysis of the TSC1-TSC2 complex’s role in stem cell fate determination and its implications for tuberous sclerosis complex. Results The TSC1-TSC2 complex plays a crucial role in various stem cells, such as neural, germline, nephron progenitor, intestinal, hematopoietic, and mesenchymal stem/stromal cells, primarily through the mTOR signaling pathway. Conclusions This review aims shed light on the role of the TSC1-TSC2 complex in stem cell fate, its impact on health and disease, and potential new treatments for tuberous sclerosis complex. Graphical abstracthttps://doi.org/10.1186/s13287-025-04170-3Tuberous sclerosis complexMammalian target of rapamycinStem cell
spellingShingle Shuang Wang
Ruishuang Ma
Chong Gao
Yu-Nong Tian
Rong-Gui Hu
Han Zhang
Lan Li
Yue Li
Unraveling the function of TSC1-TSC2 complex: implications for stem cell fate
Stem Cell Research & Therapy
Tuberous sclerosis complex
Mammalian target of rapamycin
Stem cell
title Unraveling the function of TSC1-TSC2 complex: implications for stem cell fate
title_full Unraveling the function of TSC1-TSC2 complex: implications for stem cell fate
title_fullStr Unraveling the function of TSC1-TSC2 complex: implications for stem cell fate
title_full_unstemmed Unraveling the function of TSC1-TSC2 complex: implications for stem cell fate
title_short Unraveling the function of TSC1-TSC2 complex: implications for stem cell fate
title_sort unraveling the function of tsc1 tsc2 complex implications for stem cell fate
topic Tuberous sclerosis complex
Mammalian target of rapamycin
Stem cell
url https://doi.org/10.1186/s13287-025-04170-3
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