Three dimension (3D) printed scaffolds have been shown to be superior in promoting tissue repair, but the cell-level specific regulatory network activated by 3D printing scaffolds with different material components to form a symbiosis niche have not been systematically revealed. Here, three typical 3D printed scaffolds, including natural polymer hydrogel (gelatin-methacryloyl, GelMA), synthetic polymer material (polycaprolactone, PCL), and bioceramic (đˇ-tricalcium phosphate, đˇ-TCP), are fabricated to explore the regulating effect of the symbiotic microenvironment during bone healing. Enrichment analysis show that hydrogel promotes tissue regeneration and reconstruction by improving blood vessel generation by enhancing oxygen transport and red blood cell development. The PCL scaffold regulates cell proliferation and differentiation by promoting cellular senescence, cell cycle and deoxyribonucleic acid (DNA) replication pathways, accelerating the process of endochondral ossification, and the formation of callus. The đˇ-TCP scaffold can specifically enhance the expression of osteoclast differentiation and extracellular space pathway genes to promote the differentiation of osteoclasts and promote the process of bone remodeling. In these processes, specific biomaterial properties can be used to guide cell behavior and regulate molecular network in the symbiotic microenvironment to reduce the barriers of regeneration and repair.
The underlying mechanisms of thymocyte maturation remain largely unknown. Here, we report that serine/arginine-rich splicing factor 1 (SRSF1) intrinsically regulates the late stage of thymocyte development. Conditional deletion of SRSF1 resulted in severe defects in maintenance of late thymocyte survival and a blockade of the transition of TCRβhiCD24+CD69+ immature to TCRβhiCD24âCD69â mature thymocytes, corresponding to a notable reduction of recent thymic emigrants and diminished periphery T cell pool. Mechanistically, SRSF1 regulates the gene networks involved in thymocyte differentiation, proliferation, apoptosis, and type I interferon signaling pathway to safeguard T cell intrathymic maturation. In particular, SRSF1 directly binds and regulates Irf7 and Il27ra expression via alternative splicing in response to type I interferon signaling. Moreover, forced expression of interferon regulatory factor 7 rectifies the defects in SRSF1-deficient thymocyte maturation via restoring expression of type I interferonârelated genes. Thus, our work provides new insight on SRSF1-mediated posttranscriptional regulatory mechanism of thymocyte development.
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