Prof. Brien Holden Eye Research Center, LV Prasad Eye Institute, Hyderabad 500034, India.
Center for Genetic Disorders, Banaras Hindu University, Varanasi 221005, India.
Int J Mol Sci. 2022 Jul 26;23(15):8226. doi: 10.3390/ijms23158226.
Limbus-derived stromal/mesenchymal stem cells (LMSCs) are vital for corneal homeostasis and wound healing. However, despite multiple pre-clinical and clinical studies reporting the potency of LMSCs in avoiding inflammation and scarring during corneal wound healing, the molecular basis for the ability of LMSCs remains unknown. This study aimed to uncover the factors and pathways involved in LMSC-mediated corneal wound healing by employing RNA-Sequencing (RNA-Seq) in human LMSCs for the first time. We characterized the cultured LMSCs at the stages of initiation (LMSC-P0) and pure population (LMSC-P3) and subjected them to RNA-Seq to identify the differentially expressed genes (DEGs) in comparison to native limbus and cornea, and scleral tissues. Of the 28,000 genes detected, 7800 DEGs were subjected to pathway-specific enrichment Gene Ontology (GO) analysis. These DEGs were involved in Wnt, TGF-β signaling pathways, and 16 other biological processes, including apoptosis, cell motility, tissue remodeling, and stem cell maintenance, etc. Two hundred fifty-four genes were related to wound healing pathways. (11.81 ± 0.48) and (20.44 ± 0.94) genes were exclusively up-regulated in LMSC-P3. Our findings provide new insights involved in LMSC-mediated corneal wound healing.
边缘区基质/间充质干细胞（LMSCs）对于角膜稳态和伤口愈合至关重要。然而，尽管有多项临床前和临床研究报告了 LMSCs 在角膜伤口愈合过程中避免炎症和瘢痕形成的功效，但 LMSCs 这种能力的分子基础仍不清楚。本研究旨在通过首次在人 LMSCs 中进行 RNA 测序（RNA-Seq），揭示 LMSC 介导的角膜伤口愈合所涉及的因素和途径。我们在启动阶段（LMSC-P0）和纯培养阶段（LMSC-P3）对培养的 LMSCs 进行了特征描述，并对其进行 RNA-Seq，以与天然角膜缘和巩膜组织相比，鉴定出差异表达的基因（DEGs）。在检测到的 28000 个基因中，7800 个 DEGs 进行了特定途径富集的基因本体论（GO）分析。这些 DEGs 参与了 Wnt、TGF-β 信号通路和 16 个其他生物学过程，包括细胞凋亡、细胞运动、组织重塑和干细胞维持等。254 个基因与伤口愈合途径有关。（11.81±0.48）和（20.44±0.94）基因仅在 LMSC-P3 中上调。我们的研究结果为 LMSC 介导的角膜伤口愈合提供了新的见解。
