Advances in Biological Regulation, Год журнала: 2024, Номер unknown, С. 101071 - 101071
Опубликована: Дек. 1, 2024
Язык: Английский
bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown
Опубликована: Янв. 29, 2025
ABSTRACT The bone marrow (BM) microenvironment plays a crucial role in regulating hematopoiesis, yet the molecular and functional changes associated with aging humans remain poorly understood. Using single-cell RNA sequencing (scRNA-seq), we uncovered transcriptional shifts BM endothelial cells (EC) mesenchymal stem (MSC) during aging. Our analysis revealed that aged sinusoidal EC adopt prothrombotic, exhibit mitochondrial dysfunction, have compromised vascular function. Additionally, identified unique arterial subset, present only individuals, elongation senescence processes characterized by RAB13 expression. MSC from subjects displayed an impaired matrix remodeling epithelial-mesenchymal transition, driven partly subpopulation of THY1 + profibrotic stromal absent young subjects. Aged were also increased ATP-oxidative metabolism reduced protein folding capacity. Finally, using immunofluorescent imaging spatial transcriptomics, confirmed presence senescent samples significant age-related cell-cell communication within niche. In summary, this work provides comprehensive view diversity, cellular interactions, organization MSC, offering novel insights potential targets could be exploited for preventing aged-associated humans.
Язык: Английский
Процитировано
0
Biomedicines, Год журнала: 2025, Номер 13(3), С. 607 - 607
Опубликована: Март 2, 2025
Leucine-rich repeat-containing G-protein-coupled receptor 4 (LGR4), a member of the (GPCR) family, has been implicated in various regulatory functions across multiple differentiation stages and numerous target sites bone diseases. Therefore, LGR4 is potential regulator nuclear factor-κB ligand (RANKL) during osteoclast differentiation. However, comprehensive investigation its applications immunology lacking. This review discusses molecular characteristics, signaling pathways, role osteoimmunology, with particular focus on interactions RANKL differentiation, while identifying gaps that warrant further research.
Язык: Английский
Процитировано
0
Journal of Tissue Engineering, Год журнала: 2024, Номер 15
Опубликована: Янв. 1, 2024
Stem cell factors (SCFs) are pivotal existing in both soluble and membrane-bound forms, expressed by endothelial cells (ECs) fibroblasts throughout the body. These enhance growth, viability, migration multipotent lineages. The preferential expression of SCF arteriolar ECs indicates that arterioles create a unique microenvironment tailored to hematopoietic stem (HSCs). Insufficiency within bone marrow (BM)-derived adipose tissue results decreased their overall cellularity, affecting HSCs immediate progenitors critical for generating diverse blood maintaining microenvironment. deficiency disrupts BM function, impacting production differentiation HSCs. Additionally, deleting from adipocytes reduces lipogenesis, highlighting crucial role SCF/c-kit signaling controlling lipid accumulation. This review elucidates sources, roles, mechanisms, molecular strategies renewal, offering comprehensive overview recent advancements, challenges, future directions leveraging as key agent regenerative medicine.
Язык: Английский
Процитировано
2
European Journal of Medical and Health Research, Год журнала: 2024, Номер 2(5), С. 10 - 26
Опубликована: Сен. 1, 2024
The review examines multiple myeloma, including pathophysiology, conventional treatments, current management strategies, treatment challenges, and emerging therapies. disease, originating from malignant plasma cells, leads to bone marrow infiltration osteolytic lesions. Common manifestations include anemia, pain, renal dysfunction, hypercalcemia. Pathophysiological aspects involve disrupted signaling pathways conflicts between myeloma cells the environment. Conventional such as chemotherapy with melphalan cyclophosphamide, corticosteroids (e.g., dexamethasone), autologous stem cell transplantation (ASCT), have improved patient outcomes but come significant side effects, myelosuppression infection risks. Recent advances in targeted therapies like proteasome inhibitors bortezomib) immunomodulatory drugs lenalidomide), well monoclonal antibodies daratumumab) innovative immunotherapies, CAR T-cell therapy bispecific antibodies. Precision medicine enhances by customizing based on individual genetic molecular profiles. Despite these advancements, challenges drug resistance, relapse, refractory disease persist. Resistance mechanisms, upregulation of anti-apoptotic proteins mutations affecting metabolism, hinder effective treatment. Managing relapsed or cases frequently requires reassessing strategies exploring novel Current treatments' adverse both hematological non-hematological, impact quality life, necessitating supportive care, dose adjustments, proactive education.
Язык: Английский
Процитировано
0
International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(21), С. 11653 - 11653
Опубликована: Окт. 30, 2024
The in vitro generation of spermatogonial stem cells (SSCs) from embryonic (ESCs) offers a viable approach for addressing male infertility. A multitude molecules participate this intricate process, which requires additional elucidation. Despite the decline SSCs aged testes, are deemed immortal since they can multiply three years with repeated transplantation. Nonetheless, examination aging is challenging due to limited quantity and absence precise indicators. Using microarray, we assessed genome-wide transcripts (about 55,000 transcripts) fibroblasts SSCs. WGCNA was then used look SSC-specific transcription factors (TFs) hub genes based on ATAC-seq, DNase-seq, RNA-seq, microarray data GEO databases as well gene expression (RNA-seq data). analysis human cases different revealed that 6 were upregulated, 23 downregulated compared normal case relation genes. To reach these results, online assessments Enrich Shiny GO, STRING, Cytoscape forecast molecular functional connections proteins before identifying master routes. biological process function keywords cell-matrix adhesion, telomerase activity, telomere cap complex shown be significantly altered upregulated differentially expressed (DEGs) by enrichment analysis. According our preliminary research, cell-specific TFs TF-mediated GRNs involved creation In order maximize induction efficiency ESC differentiation into vitro, important identified, sophisticated network regulation proposed. interact may able shine light pathophysiologies infertility aberrant germ cells.
Язык: Английский
Процитировано
0
Experimental Hematology, Год журнала: 2024, Номер unknown, С. 104686 - 104686
Опубликована: Ноя. 1, 2024
The present knowledge on hematopoietic stem and progenitor cell (HSPC) biology aging is based largely studies in mouse models. While models are invaluable, they not without limitations for defining how physical properties of HSPCs their niche change with age. bone marrow (BM) a complex, interactive environment multiple types. structure organization the BM niche, especially extracellular matrix (ECM), Provided recent advances quantitative analytical techniques vitro models, we have developed novel tools to quantitatively assess impact specific biochemical cues homing, adhesion migration HSPCs. Recent developments also provided new insights into interactions between particularly role stiffness. Further research needed integrate biomarkers comprehensive mathematical age-dependent HSPC-niche interactions. key use conjunction direct analyses achieve more understanding alterations function regulation.
Язык: Английский
Процитировано
0
Advances in Biological Regulation, Год журнала: 2024, Номер unknown, С. 101071 - 101071
Опубликована: Дек. 1, 2024
Язык: Английский
Процитировано
0