Neural stem cells/progenitors that give rise to neurons and glia have been identified in different regions of the brain, including the embryonic retina and ciliary epithelium of the adult eye. Here, we first demonstrate the characterization of neural stem/progenitors in postnatal iris pigment epithelial (IPE) cells. Pure isolated IPE cells could form spheres that contained cells expressing retinal progenitor markers in non-adherent culture. The spheres grew by cell proliferation, as indicated by bromodeoxyuridine incorporation. When attached to laminin, the spheres forming IPE derived cells were able to exhibit neural phenotypes, including retinal-specific neurons. When co-cultured with embryonic retinal cells, or grafted into embryonic retina in vivo, the IPE cells could also display the phenotypes of photoreceptor neurons and Muller glia. Our results suggest that the IPE derived cells have retinal stem/progenitor properties and neurogenic potential without gene transfer, thereby providing a novel potential source for both basic stem cell biology and therapeutic applications for retinal diseases.
Sarcopenia diagnosed with L3 SMI can be a negative predictor of postoperative and survival outcomes for non-metastatic CRC patients. Prospective studies with a uniform definition of sarcopenia are needed to update our findings.
The regeneration of lens tissue from the iris of newts has become a classical model of developmental plasticity, although little is known about the corresponding plasticity of the mammalian iris. We here demonstrate and characterize multipotent cells within the iris pigment epithelium (IPE) of postnatal and adult rodents. Acutely-isolated IPE cells were morphologically homogeneous and highly pigmented, but some produced neurospheres which expressed markers characteristic of neural stem/progenitor cells. Stem/progenitor cell markers were also expressed in the IPE in vivo both neonatally and into adulthood. Inner and outer IPE layers differentially expressed Nestin (Nes) in a manner suggesting that they respectively shared origins with neural retina (NR) and pigmented epithelial (RPE) layers. Transgenic marking enabled the enrichment of Nes-expressing IPE cells ex vivo, revealing a pronounced capacity to form neurospheres and differentiate into photoreceptor cells. IPE cells that did not express Nes were less able to form neurospheres, but a subset initiated the expression of pan-neural markers in primary adherent culture. These data collectively suggest that discrete populations of highly-pigmented cells with heterogeneous developmental potencies exist postnatally within the IPE, and that some of them are able to differentiate into multiple neuronal cell types.
Hepatocellular carcinoma (HCC) was the most common primary liver cancer, and its resistance to anti-tumor drugs often caused the death of patients suffering with HCC. Matrix stiffness was reported to be closely related to tumor chemoresistance; however, the relationship between HCC drug resistance and three-dimensional (3D) matrix stiffness is still unclear at present. In this study, alginate gel (ALG) beads with controllable matrix stiffness were used to mimic tumor tissue rigidity, and the role of 3D matrix stiffness in regulating the chemoresistance of HCC cells was investigated by using these ALG beads. It was found that HCC cells in ALG beads with 105 kPa stiffness had highest resistance to paclitaxel, 5-FU, and cisplatin. Although the mechanism was still uncovered, ABC transporters and endoplasmic reticulum stress-related molecules were highly expressed in ALG bead-encapsulated HCC cells compared with two-dimensional-cultured cells, which suggested a very complex mechanism underlying HCC drug resistance in 3D culture conditions. In addition, to mimic the specific stiffness of HCC tumor tissue, or other tumor tissues in vivo, response surface methodology (RSM) was used to build up a prediction mathematical model so that ALG beads with desired matrix stiffness could be prepared by simply changing three factors: molecular weight, G content, and alginate concentration.
Colorectal cancer (CRC) ranks as one of the most common malignant tumors worldwide. Its mortality rate has remained high in recent years. Therefore, the aim of this study was to identify significant differentially expressed genes (DEGs) involved in its pathogenesis, which may be used as novel biomarkers or potential therapeutic targets for CRC. The gene expression profiles of GSE21510, GSE32323, GSE89076, and GSE113513 were downloaded from the Gene Expression Omnibus (GEO) database. After screening DEGs in each GEO data set, we further used the robust rank aggregation method to identify 494 significant DEGs including 212 upregulated and 282 downregulated genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed by DAVID and the KOBAS online database, respectively. These DEGs were shown to be significantly enriched in different cancer‐related functions and pathways. Then, the STRING database was used to construct the protein–protein interaction network. The module analysis was performed by the MCODE plug‐in of Cytoscape based on the whole network. We finally filtered out seven hub genes by the cytoHubba plug‐in, including PPBP,
CXCL11. The expression validation and survival analysis of these hub genes were analyzed based on The Cancer Genome Atlas database. In conclusion, the robust DEGs associated with the carcinogenesis of CRC were screened through the GEO database, and integrated bioinformatics analysis was conducted. Our study provides reliable molecular biomarkers for screening and diagnosis, prognosis as well as novel therapeutic targets for CRC.
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