Backbone of Success

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More than two decades ago, Olivier Pourquié, biologist, found a cellular clock in chicken embryos where each “tick” triggers a forming of the somite that ends up becoming a vertebra.

In future years, Pourquié and other researchers examined closely the workings of this “so-called segmentation clock” in many organisms, including making first models resembling a clock inside “a lab dish using mouse cells.” The research has shown better understanding of “normal and abnormal spine development”, nobody has been able to verify if this type of clock is found in people until recently.

Pourquié ran two teams that made “the first lab-dish models of the segmentation clock”, using adult stem cells. 

This breakthrough not only gives primary raw information that segmentation clock ticks exist in people, but also inform the scientific community “the first in-vitro system”, allowing research on embryonic spine development in people.

We don’t know anything regarding lifespan development of somites, which emerge at around the third and fourth week post fertilization, way before most people become aware that they are pregnant, according to the biologist, and also a genetics professor at Blavatnik Institute at Harvard Medical School, who is also a main faculty member at Harvard Stem Cell Institute. He states that their system for approaching this research should be a revolutionary one to examine the “underlying regulation of the segmentation clock.”

Margarete Diaz-Cuadros, graduate student under Pourquié’s lab training, and co-author of “HMS-led paper, published January 8, in “Nature” journal,  states that innovative experimental system lets researchers “to compare mouse and human development” simultaneously. She also said that she is looking forward to demystify “what makes human development unique.”

In human induced pluripotent stem cells (iPS), the cell signaling molecules show up in green, appear every time “the segmentation clock ticks”.  

These biological models help us to understand developmental conditions occurring in the spine, such as congenital scoliosis, and diseases where tissues are involved that come from the same region of the embryo, aka paraxial mesoderm. and blood vessel lining located in the trunk and back.

Pourquié’s goal is that researchers can use “new stem cell models” to develop “differentiated tissue for research and clinical” use, in the examples of skeletal muscle cells to examine muscular dystrophy and brown fat cells to examine type 2 diabetes. This kind of work would give a starting point on coming up with new treatments and therapies. 

Pourquié states that if you want to develop and devise systems that are relevant for clinical use, you have to understand the biology first, who is also professor of pathology at Harvard Medical School. He continued by saying that muscle tissue can be made and can work.

Even though researchers have extracted many types of tissues by “retraining adult cells into pluripotent stem cells”, followed by coaxing these adult cells going with specified “developmental paths”, musculoskeletal tissues demonstrates stubborn behavior. At the end of the day, Pourquié and his team found that they can manage the change, by putting only two chemical compounds “to the stem cells”, when they are placed in a bath in an environment of standard growth culture medium.

Pourquié states that they can develop paraxial mesoderm with around 90% efficiency, and it is a very good start. His team made a similar biological model extracted from “embryonic mouse cells”. HMS researchers were shocked to discover “that the segmentation clock” started ticking “BOTH in mouse and human” petri dishes, and cells are not required to be lined up in a 3D scaffold in closer look, to look like the body.

Pourquié states, “it’s pretty spectacular that it [works] in 2D model”, and that “it’s a dream system.” His research team discovered “that the segmentation clock ticks every five hours in human cells, and every 2.5 hours in mouse cells.” Based on the authors, this difference shows gestation time between mice and humans.

Next biological research projects for Pourquié’s team, are to examine “what controls the clock’s variable speed,” and on an EVEN more ambitious move, “what” controls “the length of embryonic development in different species.” Pourquié states that there are lots of SUPER interesting problems to chase after.

Another research group published in the January 8 journal issue of “Nature”, discovered new information on how cells work in synchrony on the segmentation clock through “mouse embryos” programmed to “incorporate fluorescent proteins.”

Pourquié is the main writer for “the HMS-led paper”. Other researchers include the following: Daniel Wagner, postdoctoral researcher of HMS (co-first writer), among other writers “affiliated with Kyoto University, RIKEN Center for Brain Science, and Brandeis University”. Pourquié also has a company called “Anagenesis Biotechnologies”. They follow protocols used to create this clinical trial. They used “high through- put screening to look for cell therapies in musculoskeletal diseases and injuries.