Transforming Growth Factor-Beta (TGF-β)

Transforming growth factor-beta (TGF-β) is a multifunctional cytokine that plays a significant role in various biological processes, particularly in stem cell differentiation and regulation. TGF-β exists in three isoforms in mammals: TGF-β1, TGF-β2, and TGF-β3, and is primarily involved in cell growth, differentiation, and apoptosis.

Key Functions of TGF-β

Stem Cell Differentiation

TGF-β is crucial for regulating the differentiation of stem cells into various cell types. Its effects can be context-dependent, meaning it can either promote or inhibit differentiation based on the specific cellular environment:

– Promotion of Differentiation: TGF-β facilitates the differentiation of stem cells into lineages such as smooth muscle cells, cardiomyocytes, and chondrocytes. For instance, it has been shown to enhance the formation of immature cardiomyocytes from bone marrow stem cells [1].

– Inhibition of Differentiation: Conversely, TGF-β can inhibit the differentiation of stem cells into other lineages like myotubes and adipocytes. This dual role is essential for maintaining the balance between self-renewal and differentiation in stem cell populations [2][3].

Signaling Pathways

TGF-β exerts its effects through several signaling pathways:

– Smad Pathway: The canonical pathway involves Smad proteins (Smad2, Smad3, and Smad4), which translocate to the nucleus to regulate gene expression related to cell differentiation.

– Non-Smad Pathways: TGF-β also activates non-Smad pathways such as the MAPK pathways and PI3K/AKT pathways, contributing to its diverse biological outcomes [4][5].

Clinical Implications

The understanding of TGF-β’s role in stem cell biology has significant clinical implications. Its involvement in tissue regeneration makes it a potential target for therapies related to degenerative diseases and injuries. Additionally, dysregulation of TGF-β signaling is implicated in various diseases, including blood cancer, solid organ tumor and fibrosis [6][7].

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For further reading on TGF-β’s roles in stem cell biology, you can refer to the following articles:

1. Different Roles of TGF-β in the Multi-Lineage Differentiation of Stem Cells

This article discusses the various functions of TGF-β in stem cell differentiation through different signaling pathways, including Smad and non-Smad pathways.

DOI: [10.3892/br.2012.828] https://doi.org/10.3892/br.2012.828

2. TGF-β Signaling in the Control of Hematopoietic Stem Cells

This review covers how TGF-β signaling regulates hematopoietic stem cell behavior, including self-renewal and differentiation, highlighting its importance in both normal physiology and disease contexts.

DOI: [10.1182/blood-2013-12-516387] https://doi.org/10.1182/blood-2013-12-516387

3. Roles of TGF-β Family Signaling in Stem Cell Renewal and Differentiation

This article illustrates the roles of TGF-β family members in maintaining and differentiating embryonic and somatic stem cells, emphasizing their therapeutic potential.

DOI: [10.1038/cr2008323] https://doi.org/10.1038/cr2008323

4. TGF-β Family Signaling in Stem Cells

This review discusses the diverse roles of TGF-β signaling in regulating embryonic, somatic, and cancer stem cells, providing insights into potential therapeutic applications.

DOI: [10.1016/j.stem.2014.02.004] https://doi.org/10.1016/j.stem.2014.02.004

5. Transforming Growth Factor-β in Stem Cells and Tissue Homeostasis

This article reviews the involvement of TGF-β in tissue regeneration and its implications for maintaining stem cell function and tissue homeostasis.

DOI: [10.1038/s41413-017-0005-4] https://doi.org/10.1038/s41413-017-0005-4