| Description |
The process of embryonic stem cells differentiating into the outer, middle, and inner germ layers, along with the identification of major cytokines, signaling pathways, and transcription factors involved in the subsequent differentiation of these germ layers into neural cells and hepatocytes, has been relatively well-established. Research reports, including our prior findings, have indicated that cell metabolism plays a pivotal role in the self-renewal and fate determination of pluripotent stem cells. Nevertheless, the precise mechanisms underlying the influence of metabolites on the maintenance of stem cell pluripotency and its differentiation process remain largely elusive. This project aims to delve deeper into this phenomenon by examining embryonic stem cells, induced pluripotent stem (iPS) cells, and cells or organoids at various stages of differentiation towards neural and hepatocyte lineages. Our objectives are to identify key metabolic intermediates and pathways that govern the maintenance of pluripotency and differentiation into neural or hepatocyte cells, elucidate the specific molecular mechanisms underlying their regulation, and investigate the role of mitochondria-related proteins in the maintenance of stem cell pluripotency and their differentiation into neural tube and hepatocyte cells. To achieve these goals, we will construct knockout mouse models targeting key metabolic enzymes or mitochondria-related proteins, as well as mouse models derived from haploid stem cells, to validate the functional roles of these key metabolites, pathways, and mitochondria-related proteins in vivo. |
