Skin Stem Cells

Adult stem cells are the undifferentiated cells that are involved in the maintenance, renewal, and repair of various tissues and organs. These stem cells are found in particular niche in a tissue or an organ where they remain undifferentiated and are activated to undergo division and differentiation to maintain the tissue or when activated by disease or disruption. Skin undergoes constant renewal and it is crucial to study the dynamic pathways and key regulators involved at the transcriptional level in proliferation and differentiation of adult stem cells. In Skin, there are different adult stem cells are located in various locations and can be isolated based on their unique cell surface marker expression. Like epithelium, hair follicles also undergo constant regeneration and have a niche for adult stem cells in the bulge region. Bulge stem cells have shown to regenerate various cell types of the epidermis and when grown in vitro to have shown high proliferation and large colony formation in vitro [1]. The keratinocytes isolated also have shown to be accumulating mutations to form malignant cancers. Skin cancer is one of the most prevalent cancers in United States with around 5 million people being diagnosed and an average of 8 billion dollars is spent on the treatment for skin cancer annually. The statistics on the financial burden on skin cancer and the increasing cases of melanoma and non-melanoma cases detected each year shows the need for research and understanding the underlying mechanisms to prevent skin cancer [2].

As these adult stem cells have such unique characteristics, it is important to know about the key regulators involved in the cell proliferation, cell differentiation, immunity and pathways that lead the cells to become cancerous. Apart from the above tissue specific properties there is also a huge interest in trying to understand universal adult stem cells property and their involvement in cancer. With advances in high throughput sequencing, we are now able to study differential gene expression across various cells and tissues. Deeper sequencing techniques have enabled to sequence the major chunk of the genome which is non-coding transcriptome. RNA-sequencing has made it easy to compare gene expression profiles across samples and in-between two cell types from the same tissue and gives an insight into gene expression, tissue pattern or cell specificity of both protein coding genes and non-coding genes. Having this data will help us understand the key regulators which participate in stem cell proliferation, differentiation and in our study, genes involved in high colony formation. By isolating specific stem cells from mouse model, it will help us design an experimental model which will allow us to compare the data with publicly available data bases to understand the roles and functions of key regulators involved.

Among the non-coding RNAs, long non-coding (lncRNA) RNAs have shown to be involved in regulation, stem cell differentiation and tumor promotion. With increasing evidences of lncRNA's involvement in gene regulation, we decided to look into them and how they are differentially expressed and affect the nearby protein coding genes in our cells of interest from the C57BL6 mouse. LncRNA's are more than 200 bp in length and are involved in gene regulation at transcriptional and post-translational level. They bind with proteins, transcription factors and by binding with other ncRNA alter gene expression. It is also known that lncRNA are tissue specific and are differentially expressed in higher numbers compared with protein-coding genes [3]. In databases like Gencode, they have reported a total of 28468 lncRNA genes in human and 17855 lncRNA genes in mouse [4]. Most of the functions of lncRNAs are still unknown. Identifying differentially expressed genes will be the first step to look into important genes and pathways that regulate the stem cell characteristics of hair bulge cells compared to the nearby non-stem cell population. To understand better how Long non-coding and mRNA work in the skin we are including parameters like the location of lncRNA and gene expression pattern of selected lncRNA-mRNA across different cancer types to know the function and possible regulatory mechanism of lncRNA on nearby protein-coding genes. Keratinocyte stem cells and cancer

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