The Effects of Molecular Glue on Cell Pluripotency

The Effects of Molecular Glue on Cell Pluripotency ...

The cells in the body known as pluripotent stem cells are yet to specialize in a specific biological function. These cells maintain the potential to become any of the possible cell types in an organism. NANOG, a powerful protein, has shown great promise in regenerative and transplant medicine for their properties, including unlimited self-renewal. This protein is the foundation of pluripotent stem cells and is a necessity to reintroduce specialized cells into tiny, untrained stem cells. The nature of this process

In the journalNature Cell Biology, researchers look into the mechanism of how human NANOG assists cell pluripotency. These cells interact with chromatin strings of DNA and proteins that funnel to the genome to transform the genomic landscape in a manner that activates a pluripotent state.

Adding specialized cells to a pluripotent state requires massive reorganization of the chromatin and changes in gene expression, according to acorresponding author. Dr. Josephine Ferreon, an assistant professor in medicine and chemical biology, has found that coordinated gene activation often requires bringing DNA elements closer to the desired outcome. NANOGs has a naturally floppy, flexible 3D shape, and a C-terminal tail that is structurally similar to prion-like proteins to this goal

Studying NANOG poses significant challenges

The strong tendency to self-adhere and aggregate in NANOG poses a challenge for traditional ensemble methods that require high protein concentrations. The team resorted to highly sensitive fluorescence strategies to investigate this very challenging protein.

We used single molecule and fluorescence fluctuations microscopy techniques to visualize whether two molecules interact with each other. During experiments, we observed that with NANOG, even at very low concentrations, we still discovered aggregation. Nevertheless, we were able to demonstrate that NANOG aggregation is actually necessary to its function as a master transcription factor and a mediator of DNA bridging.

We believe this fact is the foundation of NANOG expression that is fundamental to the establishment of pluripotency. When NANOGs levels are low, cells are prone to differentiate, and when its level is high, the ground pluripotent state or full reset is achieved and maintained, according to Dr. Josephine Ferreon.

NANOG aggregates are similar to those of amyloids, which are culpable for Alzheimer''s disease and other neurodegenerative disorders. However, the aggregates are not associated with a harmful condition, but with an essential cellular process, the activation of cell pluripotency. A growing number of studies suggests that not all amyloids are harmful, but some may be rather functional.

NANOG, a molecular glue, may instill and stabilize key chromatin interactions that are important for the pluripotent state, according to the researchers. Its role as a molecular hub protein as well as its interactions with many key chromatin regulators that are involved in opening chromatin and discovering and modifying specific chromatin regions

To alter the genomic landscape, we hope to seek out further knowledge about NANOG''s role in recruiting or cooperating with important transcription factors, coactivators, and epigenetic modulators.

Kyoung-Jae Choi, My Diem Quan, Chuangye Qi, Joo-Hyung Lee, Phoebe S. Tsoi, Mahla Zahabiyon, Aleksandar Bajic, Liya Hu, B. V. Venkataram Prasad, Shih-Chu Jeff Liao, and Wenbo Li.

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