Direct Reprogramming of Various Somatic Cell Types into Fibroblasts Cells Using Transcription Factors: A Potential Cure for COPD and Chronic Wound Healing
by Akshara Karthik
Category: STEM
Abstract – In the United States, 6 in 10 adults suffer from chronic diseases, like diabetes and chronic obstructive pulmonary disease (COPD), with resultant poor wound healing abilities and irreversible lung damage (Chronic Diseases, 2021). Direct cell reprogramming, could potentially reverse the effects of lung damage caused by smoking, as well as quicken wound healing. This novel project aimed to identify transcription factors to directly reprogram various somatic cell types into fibroblasts. Fibroblast cells actively participate in tissue repair and wound healing. Ten transcription factors associated with fibroblasts were identified through the online database Amazonia! and their functions were researched through GeneCards: MMP3, ID1, SNAI2, FGF2, SP1, FAP, FIBP, PRRX1, LBH, and AEBP1. Each of the transcription factors were further explored to confirm that high gene expression was limited to fibroblasts. This will ensure that the use of the chosen transcription factors would lead to fibroblast production rather than an undesired cell type. The National Center for Biotechnology Information (NCBI) and KEGG Pathway Databases were then employed, to study the metabolic pathways (both disease and regulatory) that each of the selected transcription factors are involved in. Metabolic pathways were analyzed to eliminate any transcription factors that are involved in known disease pathways, deeming them not suitable for direct cell reprogramming. Overall, SNAI2 and ID1 were identified as the ideal transcription factors to directly reprogram somatic cells into fibroblasts, because they have limited association with diseases and are not highly expressed in other cell types.