The Functions and Mechanisms of the Cohesin Complex in Regulating the Fate Determinations of Stem Cells

Stem cells have important applications in both regenerative and reproductive medicine. The cohesin complex comprises 4 core subunits, namely, SMC1, SMC3, RAD21, and STAG, and notably, it plays pivotal roles in controlling the fate determinations of stem cells by facilitating the dynamic regulation o...

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Main Authors: Jianghong Xiang, Yihan Lai, Zuping He
Format: Article
Language:English
Published: American Association for the Advancement of Science (AAAS) 2025-01-01
Series:Research
Online Access:https://spj.science.org/doi/10.34133/research.0757
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author Jianghong Xiang
Yihan Lai
Zuping He
author_facet Jianghong Xiang
Yihan Lai
Zuping He
author_sort Jianghong Xiang
collection DOAJ
description Stem cells have important applications in both regenerative and reproductive medicine. The cohesin complex comprises 4 core subunits, namely, SMC1, SMC3, RAD21, and STAG, and notably, it plays pivotal roles in controlling the fate determinations of stem cells by facilitating the dynamic regulation of the 3-dimensional genome architecture. We have recently reported that RAD21 forms a complex with YAP1 and NEDD4 to promote the self-renewal of human spermatogonial stem cells and inhibit their apoptosis. In this review, we address the molecular properties of the cohesin complex and its multiple regulatory mechanisms in mediating the fate decisions of various kinds of stem cells, including hematopoietic stem cells, embryonic stem cells, spermatogonial stem cells, neural stem cells, and other types of stem cells. By maintaining the chromatin loop structure, the cohesin complex is involved in DNA repair and gene transcription, which in turn controls the pluripotency, self-renewal, and differentiation of stem cells. In addition, the cohesin complex ensures faithful DNA replication and sister chromatid cohesion, which indirectly supports genetic and epigenetic programs. Variants in the subunit components of the cohesin complex and proteins’ modifications further confer functional plasticity, and its mutations can lead to abnormal stem cell functions and are correlated with diseases including cancers. Future studies need to integrate multidisciplinary approaches including single-cell multi-omics and cryo-electronic microscopy to resolve the dynamic regulatory networks of the cohesin complex in stem cell fate regulation and further explore its potential applications in regenerative and reproductive medicine.
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spelling doaj-art-f5e0977cbc5b4cc0b98bfc3d82110c022025-08-20T02:36:00ZengAmerican Association for the Advancement of Science (AAAS)Research2639-52742025-01-01810.34133/research.0757The Functions and Mechanisms of the Cohesin Complex in Regulating the Fate Determinations of Stem CellsJianghong Xiang0Yihan Lai1Zuping He2Key Laboratory of Model Animals and Stem Cell Biology in Hunan Province, Engineering Research Center of Reproduction and Translational Medicine of Hunan Province, Institute of Interdisciplinary Studies, Hunan Normal University School of Basic Medicine, Hunan 410013, China.Key Laboratory of Model Animals and Stem Cell Biology in Hunan Province, Engineering Research Center of Reproduction and Translational Medicine of Hunan Province, Institute of Interdisciplinary Studies, Hunan Normal University School of Basic Medicine, Hunan 410013, China.Key Laboratory of Model Animals and Stem Cell Biology in Hunan Province, Engineering Research Center of Reproduction and Translational Medicine of Hunan Province, Institute of Interdisciplinary Studies, Hunan Normal University School of Basic Medicine, Hunan 410013, China.Stem cells have important applications in both regenerative and reproductive medicine. The cohesin complex comprises 4 core subunits, namely, SMC1, SMC3, RAD21, and STAG, and notably, it plays pivotal roles in controlling the fate determinations of stem cells by facilitating the dynamic regulation of the 3-dimensional genome architecture. We have recently reported that RAD21 forms a complex with YAP1 and NEDD4 to promote the self-renewal of human spermatogonial stem cells and inhibit their apoptosis. In this review, we address the molecular properties of the cohesin complex and its multiple regulatory mechanisms in mediating the fate decisions of various kinds of stem cells, including hematopoietic stem cells, embryonic stem cells, spermatogonial stem cells, neural stem cells, and other types of stem cells. By maintaining the chromatin loop structure, the cohesin complex is involved in DNA repair and gene transcription, which in turn controls the pluripotency, self-renewal, and differentiation of stem cells. In addition, the cohesin complex ensures faithful DNA replication and sister chromatid cohesion, which indirectly supports genetic and epigenetic programs. Variants in the subunit components of the cohesin complex and proteins’ modifications further confer functional plasticity, and its mutations can lead to abnormal stem cell functions and are correlated with diseases including cancers. Future studies need to integrate multidisciplinary approaches including single-cell multi-omics and cryo-electronic microscopy to resolve the dynamic regulatory networks of the cohesin complex in stem cell fate regulation and further explore its potential applications in regenerative and reproductive medicine.https://spj.science.org/doi/10.34133/research.0757
spellingShingle Jianghong Xiang
Yihan Lai
Zuping He
The Functions and Mechanisms of the Cohesin Complex in Regulating the Fate Determinations of Stem Cells
Research
title The Functions and Mechanisms of the Cohesin Complex in Regulating the Fate Determinations of Stem Cells
title_full The Functions and Mechanisms of the Cohesin Complex in Regulating the Fate Determinations of Stem Cells
title_fullStr The Functions and Mechanisms of the Cohesin Complex in Regulating the Fate Determinations of Stem Cells
title_full_unstemmed The Functions and Mechanisms of the Cohesin Complex in Regulating the Fate Determinations of Stem Cells
title_short The Functions and Mechanisms of the Cohesin Complex in Regulating the Fate Determinations of Stem Cells
title_sort functions and mechanisms of the cohesin complex in regulating the fate determinations of stem cells
url https://spj.science.org/doi/10.34133/research.0757
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