This study was jointly completed by the Harvard University FAC System Biology Research Center, the Stem Cell and Regenerative Biology Department, and the corresponding author is Sharad Ramanathan, a professor of molecular and cellular biology at Harvard University.
The fertilized egg is divided into many small cells through cleavage. These hollow spherical bodies composed of small cells are called blastocysts. Blastocyst cells migrate and transform to form gastrointestinal embryos, which are composed of three layers of cells: ectoderm, mesoderm, and endoderm. For the first time, the pluripotent state formed by cells in the primitive ectoderm cells of the blastocyst stage embryo will be lost in subsequent development. At present, scientists do not know the transcriptional regulation mechanism during the transition from pluripotency to differentiated cell state.
In this article, the researchers analyzed how mouse embryonic stem cell ESCs lose this pluripotency and how to choose between the various germ layers. They analyzed the dynamics of the transcription cycle that maintains pluripotency, and found that the two proteins, Oct4 and Sox2, can maintain the characteristics of ESCs and regulate the choice of germ layer.
Oct4 is an important stem cell regulatory protein. Previous studies have found that this protein can bind to transcription factors in genes to keep stem cells pluripotent. Oct4 can have different mechanisms of action. During the binding with transcription factors, The combination of some small molecules can cause chemical changes in the protein. Some researchers also suggested that Oct4 does not have the function of regulating adult stem cells. The SOX2 protein is also a transcription factor widely concerned in stem cell research and an important regulator of self-renewal of undifferentiated embryonic stem cells.
The researchers found that Oct4 can inhibit neuroectodermal differentiation and promote mesendodermal differentiation, while Sox2 can inhibit mesendodermal differentiation and promote neuroectodermal differentiation. The organism sends out different signals constantly, regulates the expression levels of Oct4 and Sox2 proteins, and changes the way they are combined in the genome to control the direction of differentiation.
These findings provide a new perspective for the regulation of embryonic stem cell differentiation and help scientists to better understand the network of transcription factors that regulate cell fate in progenitor cells.
The Ramanathan research team also achieved important results in the field of optogenetics. They used optical and genetic methods to track the effects of mutual excitation or inhibition between neurons, revealing the mechanism of neuron communication in living animals.
This new method provides a powerful tool for the analysis of small neural pathways and can directly measure the communication between neurons. The researchers hope that this technology will eventually be more widely used to detect the spread of activity in neural pathways.
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