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



            aspect of this signaling system. For instance, many GPCRs   before transplantation would considerably broaden the
            and heterotrimeric G proteins, in addition to pathways   utility of this stem cell source. While stem cell expansion
            such as hedgehog, hippo, and prostaglandins signaling,   can also be achieved in vivo following the revascularization
            interact with tumor progression and are frequently   of the transplanted cells, this strategy may present
            implicated in cancer. Despite this understanding, the   greater risks than  ex vivo expansion unless the growth
            precise role of the GPCRs in interpreting environmental,   stimuli employed  in vivo are carefully controlled.  The
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            dietary, and microbiome signals to regulate epithelial stem   attractiveness of  ex vivo stem cell expansion lies in the
            cell fate is an enthralling yet understudied topic. A deeper   precise definition of culture conditions and the ease with
            understanding  of the  specific GPCRs,  their  signaling   which transitory modification of regulatory pathways can
            partners, and the cellular mechanisms involved will be   be exploited in vitro. However, this strategy has proven to
            crucial for developing therapeutic strategies targeting   be quite difficult because complete stem cell proliferation
            intrinsic stemness pathways associated with malignant   requires symmetric self-renewal divisions of HSCs, where
            transformation and  tumor  growth.  GPCR  signals  exert   both daughter cells retain HSC characteristics.  In vitro-
            a long-lasting influence on the fate of epithelial stem   grown HSCs typically divide asymmetrically, producing
            cells, transiently and simultaneously activating multiple   one HSC and one more differentiated progenitor cell,
            pathways that desensitize receptors and halt intracellular   or symmetrically, producing two progeny cells that are
            cascades.  Therefore, a comprehensive comprehension of   no longer capable of becoming HSCs. The equilibrium
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            the interactions between GPCR signaling, transcriptional   between HSC proliferation and quiescence is ultimately
            regulation, and cellular differentiation will shed light   maintained by positive and negative regulators. 59
            on the processes that maintain stem cell characteristics   Activating pathways that promote HSC self-renewal
            and the strategies employed by stem cells to adapt to   and/or inhibit those that lead to HSC quiescence,
            microenvironmental alterations.  In the body, the   differentiation, or apoptosis should be a key component
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            epidermis serves as a protective barrier against external   of stem cell expansion efforts. Recent advancements
            environmental aggressors, microbial invasion, and   in  understanding  stem  cell  self-renewal  mechanisms
            other threats. The basal layer of the epidermis harbors   have enabled the development of new techniques for
            proliferating, immature ESCs, while multiple layers of   expanding stem cells, some of which require viral
            differentiated, non-proliferating suprafacial cells constitute   vector-mediated gene transfer for effective growth.  For
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            the upper layers.                                  safety, it is ideal that the vectors induce transitory gene
              Cornified cells from the outer layer are continually   expression and are non-integrating. Secure methods for
            replenished through the mitotic activity of ECSs, requiring a   stem cell expansion often use soluble components such
            delicate balance between self-renewal and differentiation in   as  cytokines,  developmental  cues,  or  angiopoietin-like
            the adult epidermis to maintain epidermal homeostasis and   (Angptl) proteins. Jagged, a soluble version of the Notch
            a functional barrier. Extensive research has been dedicated   ligand, promotes the expansion of severe combined
            to understanding how ESCs respond to the demands of   immunodeficient repopulating cells, making it a
            tissue growth and homeostasis, as well as the regulatory   potential tool for ex vivo stem cell expansion. However,
            mechanisms  orchestrating  these  changes.   This  section   the most promising soluble factors for murine HSC
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            discusses recent research on the regulation of the ESC during   growth identified to date are the Angptl proteins. Angptl
            development  and  their  dynamics in  adult  homeostasis,   proteins may prove useful for future cell and gene therapy
            arguing that the microenvironment solely dictates the fate   techniques if they can increase human HSCs as effectively
            of hematopoietic stem cells (HSCs). Instead, intrinsic and   as they do in the mouse system. Fibroblast growth factors
            environmental signals collaboratively affect HSC behavior.   are also particularly important to highlight because they
            The concept of the stem cell niche integrates these aspects   have been proven to support and preserve the primitive
            into a more comprehensive and holistic framework. For   phenotype of murine HSCs in culture. 61
            patients in need of blood and marrow transplants, the search   It should be underlined that studies in mice have
            for donors with appropriate histocompatibility antigens   provided most of our knowledge concerning stem cell
            can  frequently pose  significant  challenges.  Cord blood   growth. Mouse and human stem cells differ in cytokine
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            (CB)  cells,  now  widely  available  and  containing  various   receptors, proliferative potential, and telomere biology,
            histocompatibility gene haplotypes, are increasingly being   leading to both differences and parallels in strategies for
            recognized as a valuable source of human stem cells. 57  increasing HSCs. Nephroblastoma overexpressed should

              Since there are only a limited number of HSCs in each   be considered for clinical stem cell growth techniques, as
            CB sample, the capacity to grow CB stem cells  ex  vivo   it can expand primitive HSCs. Small molecule medications


            Volume 3 Issue 2 (2024)                         12                              doi: 10.36922/gpd.2996
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