Laser for differentiation of embryonic stem cells
The fate of stem cells learned to control with a laser
Their findings were published in the journal Cell Systems (Sokolik et al., Transcription Factor Competition Allows Embryonic Stem Cells to Distinguish Authentic Signals from Noise), and they are briefly described on the website of the University of California at San Francisco (UCSF Researchers Control Embryonic Stem Cells With Light).
In addition, Matthew Thompson (Matthew Tompson) from the University of California and his colleagues revealed another curious feature of the life and work of stem cells – it turned out that they are equipped with a kind of "timer" and a signal filtering system that protects them from arbitrary transformation into adult tissue blanks due to signaling molecules accidentally trapped in their surroundings.
This discovery simultaneously solves the mystery of why stem cells remain stable during embryo development, despite the "unauthorized" sporadic inclusion of growth genes, and may help scientists learn how to better manage the transformation of their cultures into organs and tissues.
Thompson's group discovered all this by experimenting with embryonic stem cells extracted from the embryos of mice whose genome was modified in such a way that one of the growth genes in them could be turned on using blue laser pulses. This gene, BRN2, contains genetic "instructions" that include a program for converting stem cells into neurons and nerve tissue.
Stem cells irradiated with blue light. Image: Elizabeth MooneyExperimenting with cultures of these cells, scientists noticed something extremely unusual.
To their surprise, the cells reacted to the light pulses not immediately, but after a while. The length of this delay depended on the strength and duration of irradiation – if the cells were "illuminated" not long enough or strongly, then they did not respond at all to the commands of scientists.
Thompson and his team uncovered the work of this cellular "stopwatch" using the increasingly popular genome editing system – CRISPR/Cas9. With its help, the researchers marked the NANOG gene, the main "brake" for the transformation of stem cells into other tissues. A section of DNA encoding a fluorescent protein label was attached to the NANOG sequence. This allowed scientists to use a microscope to monitor how a stem cell makes a decision – to turn or not to turn into a mature cell, and where the "stopwatch" is located at this moment.
As it turned out, nanog really works as a "timer" – when a cell is irradiated with light, its concentration begins to fall until it reaches a critical point, when differentiation mechanisms are triggered and the stem cell begins its transformation into a given mature cell type. If the irradiation stops, then the number of protein molecules quickly grows to the previous levels, and the program of transformation into neurons does not start.
Thompson hopes that the discovery of this system and the "connection" of the optical signaling system to stem cells will help realize his dream – growing three-dimensional organs from the "soup" of stem cells. To do this, you will need to teach stem cells to recognize light rays of different colors, each of which will correspond to a program for turning into a separate type of tissue.
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26.08.2015