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Gene & Protein in Disease β-cell regeneration and stem cell niche

subtle process, and the serine-threonine phosphatases of environmental damage. In the skin, basal keratinocyte
the PP2A family serve as crucial regulators of numerous stems and progenitor cells are intricately regulated by
signaling pathways associated with cancer, self-renewal, various GPCRs and their signaling partners within the
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and stem cell viability. Given the high specificity of intermolecular epidermis and hair follicles. GPCRs
each regulatory component, along with their high translate extracellular signals into intracellular molecular
degree of similarity, studies involving knockdown and cascades that govern the activation of networks involved
overexpression must carefully consider compensatory in keratinocyte proliferation and differentiation, such as
mechanisms. WNT/β-catenin, HH/GLI, and Hedgehog/Yes-associated
protein 1. These pathways collectively affect stem cell
Biomechanics emerges as a novel regulator of stem cell
fate, offering a simplified approach to identifying molecular characteristics, their activation being both dependent on
and independent of heterotrimeric G proteins. A classic
mechanisms and interactions between biomechanics example of a GPCR-associated cancer is smoothened-
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and stem cells. In addition, this advancement not only driven basal cell carcinoma, underscoring the significant
sheds light on stem cell biology but also holds promise for role of GPCRs in pathological conditions.
driving progress in regenerative medicine by influencing
the biomechanical regulation of stem cell fate. GPCRs Dysregulation of GPCR signaling underlies various
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utilize multiple signaling pathways to communicate inflammatory skin conditions and skin cancers.
from the plasma membrane. The GPCR organization at Consequently, extensive explorations have been conducted
the cell surface is essential for controlling the signaling to elucidate how GPCRs and their signaling partners affect
effects of receptor activation, as it regulates the interaction the biology of skin keratinocytes, especially concerning
of specific effector proteins with particular receptors. the regulation of the niche that contains ESCs. In general,
Furthermore, the dynamic interaction with proteins GPCRs play a crucial role in every aspect of ESC biology,
and transmembrane microdomains influences GPCR including the maintenance of the adult epithelial stem cell
organization. In addition, the endolytic rate of GPCRs, characteristics, facilitation of communication between
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which impacts receptor signaling, is ligand- and receptor- stem cells and their niche, and integration of extrinsic
dependent. This understanding of the fundamental signals to support stem cells’ capacity for contextual
structure of GPCRs in the plasma membrane, along adaptation. While attempts have been made to correlate
with how endocytosis and signaling are affected by this the functions of GPCRs and their ligands with the control
structure, is essential. For appropriate tissue development of stem cells, more specialized models that study the role
and homeostasis, precise regulation of cell division and fate of receptors in stem cell destiny must be utilized, such as
decisions is necessary. Epithelial stem cells play a crucial those involving the overexpression or knockout of GPCRs
role in maintaining the highly organized tissue structure in certain stem cell niches. 51
of the mammalian epidermis. Epithelial stem cells strike Furthermore, single-cell analysis techniques with
a balance between cell fate and self-renewal decisions to enhanced sensitivity for detecting under expressed genes
build a protective barrier. Recent research has revealed could provide a better understanding of the GPCRs
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new information on the regulatory systems that govern the regulated in each niche of ESCs. In addition, given the
specification, self-renewal, and maintenance of epithelial species-specific difference in skin structure, immunological
stem cells. These discoveries deepen our understanding modulators, and GPCR genes, further research is
of the essential mechanisms enabling epithelial stem cells warranted to validate findings from mouse models in
to establish a functional barrier during formation and human skin biology. While this review concentrated
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preserve tissue homeostasis in adults, thereby enhancing on the functions of nonsensory GPCRs, it is noteworthy
the understanding of the role of epithelial stem cells in that keratinocytes possess sensory receptors such as light-
organisms. activated opsins (melanopsin and neuropsin). GPCRs
The continuous integration of information from activated by various nutrients and microbial compounds
both the micro- and macro-environment is crucial for may establish a link between nutrition, the microbiome,
adapting to changing circumstances, preserving tissue and somatic stem cells, suggesting a potential connection
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homeostasis, and triggering repair mechanisms in somatic between these factors. A fascinating yet understudied
stem cells. GPCRs enable this integration by affecting a topic is the specific function of GPCRs in translating
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complex network of pathways that regulate stem cell fate information from the environment, food, and microbiome
through their affinity for various hormones, metabolites, to determine epithelial stem cell fate.
and inflammatory mediators. This role is particularly The role of GPCR signaling in regulating tumor
vital in tissues such as the skin, which are susceptible to development and suppression represents a remarkable

Volume 3 Issue 2 (2024) 11 doi: 10.36922/gpd.2996