The field of embryonic stem cell research remains synonymous with both controversy and great promise. Researchers at the University of California San Francisco (UCSF) have recently made a groundbreaking contribution to the field by harnessing the power of light to control embryonic stem cell differentiation.
This is the first time such a method has been developed in the field. Specifically, very precise external cues facilitated by light beams lead to cell differentiation, thus transforming stem cells into neurons.
Throughout the process of embryonic development, timing is everything when it comes to determining the fate of the initially undifferentiated cells. Cells can be influenced by and/or exposed to multiple cues and signals which has posed a particular challenge for researchers who are aiming for specific cell outcomes. This dynamic is referred to as “noise” and the researchers at UCSF have also shed light on the existence of an internal timer that stem cells possess which functions as a dial to fine tune the noise in response to a consistent and appropriate molecular signal. This ultimately results in the construction of all the major organs systems within the body.
Matthew Thomson, PhD, is a senior researcher on the project in the department of Cellular and Molecular Pharmacology and the Center for Systems and Synthetic Biology. Thomson and colleagues conducted their research using engineered cultured mouse embryonic stem cells. Pulses of blue light were used to turn on a specific gene called Brn2 which is a powerful differentiation cue for neural development. Researchers adjusted the strength and duration of the Brn2 gene’s exposure to the light pulses and monitored the cells reaction to the different dosages.
In addition, the research team was able to observe that the transcription factor Nanog plays a key role in the cells’ internal timing function through the process of differentiation. By working in a molecular feedback loop, when Brn2 turns on, it destabilizes cell stability and allows for differentiation. As a result, Nanog protein levels decrease. It normally takes a period of about four hours, for the Nanog protein to completely dissipate, and this dynamic serves as an efficient cue for signaling the end of cell differentiation. For example, if the Brn2 signal is not strong enough, the cell experiences a sharp increase in Nanog protein levels and the cell does not proceed forward.
In contrast, if Nanog levels completely dissipate while the cell continues to receive the Brn2 signal, the cell proceeds forward into rapid differentiation into neurons. These discoveries have raised hope for the future of stem cell research, and has great potential for leading scientists closer to repairing damaged tissues, and finding effective treatments for neurodegenerative diseases.
Watch the embryonic stem cell differentiation in action:
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