New insights into how transcription factors impact the identity and function of insulin-producing beta cells in the pancreas have been discovered in a study conducted by the laboratory of Joseph Bass, MD, Ph.D. The findings, published in Cell Metabolism, shed light on the role that a cell’s circadian clock plays in regulating insulin production.
Previous research conducted by Bass and his team found that the circadian clock, which consists of transcription factors that control gene activity on a 24-hour cycle, is vital for beta cells to regulate insulin production in the pancreas. The current study aims to understand how this circadian timing influences the type and function of cells within multicellular tissues, like the pancreas.
Using single-cell sequencing, the researchers analyzed beta cells from human islet cells, which are clusters of cells in the pancreas containing beta and other hormone-producing cells. They observed two distinct molecular signatures: an inflammatory state that promotes cell survival, and a cell signaling state that supports cell function.
Benjamin Weidemann, a student in the Medical Scientist Training Program and lead author of the study, explained, “We had always known that the circadian clock, at least in the beta cell, was really important, but here we discovered that there seems to be an additional role to help reinforce or control cell identity and help it possibly switch between these two different states: this inflammatory state and this more lineage-determining state where it appears to be more functional.”
In mouse models, the researchers found that the transcription factor PDX1, which plays a crucial role in the development of beta cells, interacts with these pathways to suppress inflammation signaling. This protects beta cells from stress and inflammation and supports proper function and growth.
Joseph Bass, the Charles F. Kettering Professor of Medicine and chief of Endocrinology, explained, “If beta cells begin to lose their function as insulin-producing cells, what emerges is a set of genes that are involved in determining whether a cell survives or dies and belong to the signal transduction pathways that we call inflammatory.”
The findings of the study may have implications for metabolic diseases such as type 2 diabetes and type 1 diabetes. This new understanding of the role of transcription factors could inform future therapeutic strategies for these conditions.
Bass also noted that the principles uncovered in the study may have wider applications in different tissues, particularly in immune cells. The mechanisms involved in determining cell identity, sustaining that identity, and controlling cell growth are common processes that may be relevant in various tissue contexts.
Overall, this study underscores the importance of transcription factors in regulating the function and identity of insulin-producing beta cells. By furthering our understanding of these processes, researchers may be able to develop new treatments for metabolic diseases like diabetes.
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1.Source: Coherent Market Insights, Public sources, Desk research
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