Scientists know that developing cells in a healthy embryo transforms them into the different cell types that make up the different organ systems of the human body. This is a process known as cell differentiation. But they don’t know how cells do it.
South Carolina Medical College (MUSC) Study Cell report Stephen Duncan, D. Phil.How are endoderm cells (a type of developing cell) led by Hepatocytes Not another type of cell. Duncan and his team discovered that the development of naive cells into differentiated hepatocytes depends on the transcription factor GATA6. Duncan is the chair of regenerative medicine donated to SmartState and the chair of MUSC’s Regenerative Medicine and Cell Biology Division.
“We found that this particular transcription factor, GATA6, has an anomalous mechanism because it is recognizable. Regulated area “Turn on DNA before a particular gene is turned on,” Duncan said. “Rather than turning on gene expression directly, it turns on when cells encounter proper developmental cues. Mark the gene as something that can be done. “
Duncan’s lab modeled different stages of development using human pluripotent stem cells, which can differentiate into all types of human cells. To isolate the molecular basis of cell differentiation, we gave human pluripotent stem cells growth factors and exposed them to clues specific to liver development. cellDuncan and his team cut GATA6 from the genome using a CRISPR / Cas9 gene editing tool like molecular scissors.Next, the loss of GATA6 Cell differentiation Path.
“In the absence of GATA6, we found that the area surrounding the gene remained closed and inaccessible,” Duncan said. “GATA6 can open chromatin around the regulatory regions of genes that are finally expressed as cells begin to differentiate.”
Duncan believes that this finding can provide insight into how hereditary liver disease, such as metabolic liver disease, occurs in children.
“This gives us unique insights into how the human liver develops and what goes wrong, especially in the case of hereditary liver disease,” he said.
James A. Heslop et al, GATA6 define endoderm fate by controlling the accessibility of chromatin during the differentiation of human induced pluripotent stem cells. Cell report (2021). DOI: 10.1016 / j.celrep.2021.109145
South Carolina Medical College
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