Neuron published a paper: "Starburst Amacrine Cells" Control Cell Fate

The fireworks were in full bloom, illuminating the night and the eyes of the audience To be able to appreciate the hundreds of changes of light in the blink of an eye, thanks to our retina There are nearly a hundred different types of nerve cells on the retina, which are connected into a complex neural network to transmit and integrate signals at full speed, so that the brain can sense the scene seen by the eyes in real time In these retinal cells, there are some pairs of neurons, one of which responds when the light increases and the other responds when the light decreases Such a setting is very important for us to perceive the light and dark changes A pair of cells that look the same as a mirror but have the opposite function is an interesting and difficult puzzle for developmental biologists Just like some people encounter a "noble" when they grow up and change their life path, what genes will be the key to determine the fate of cells on the road of cell development? In a recent paper published by neuron, a leading academic journal, scientists from Harvard University and Johns Hopkins University worked together to find a switch to control the fate of cells in a pair of retinal nerve cells by adopting new technology strategies In this study, Dr Peng Yirong, the first author, and his colleagues focused on nerve cells, which also looked like fireworks, named "starburst amacrine cells" (SAC) by neuroscientists The same type of fireworks may bloom at different heights after liftoff, and this sac cell will also migrate to different locations of the cell layer from the birthplace with the development of the retina However, the arrangement of life should be more orderly, and the location, structure and function of cells are closely linked A pair of sac cells migrated to the adjacent cell layer and added neural network to respond to the enhanced light (on type) and the decreased light (off type), respectively However, except for the differences of relative positions, the past methods can hardly distinguish them Since sac was discovered in 1970s, they have been regarded as a pair of cells of the same type One of the main leaders of the research team is Professor Joshua R SANEs, a well-known neuroscientist who has made a lot of breakthroughs in the research of retinal cells Earlier this year, using a technique called high-throughput single cell RNA sequencing, the team first created a pattern classification map of primate retinal cells The academic Jingwei team also introduced this work to readers before So can the new technology provide more clues to the differences between pairs of cells? This study gives a beautiful answer In order to find out the molecular differences between ON-type sac and off-type sac, Dr Peng Yirong and his colleagues analyzed more than 2000 sac cells in different development stages by means of scrna SEQ, and divided them into two groups according to the differences of gene expression, and determined that the two types with different gene expression profiles are the corresponding on / off types How to find out the key genes of different destiny from these differentially expressed genes? The researchers concluded that transcription factors regulate the expression of other genes, which can control the development process of cells If a transcription factor only exists in one group of cells in the early stage of development, it is likely to be the key to guide the cells to the final fate Therefore, researchers focus on finding transcription factors that meet this condition They found their first target: fezf1 In the early sac cells after mitosis of sac precursor cells, half of them expressed this transcription factor At the later stage of development, the half of fezf1 expression migrated to the position close to the inner edge and became the on type; on the contrary, the half of fezf1 expression lacking cells remained in the position relative to the outer edge and became the off type Then a group of experiments confirmed that fezf1 is the fate switch that controls sac to be on or off! When the researchers removed it from the on cells, the cells became off; when they put it into the off cells, the cells became on "This transformation is not only the change of on / off position, but also the complete reversal of on / off gene expression profile." Dr Peng said So, among the various genes regulated by transcription factor fezf1, is there a downstream gene specifically responsible for the migration of on and off type cells to different locations? The team returned to the data of scrna SEQ and found another gene, Rnd3 As a part of fezf1 controlling the downstream program, it controls the migration of different sac Based on these results, the author takes sac of retina as an example, combing out a set of gene programs in a haystack, revealing how a pair of similar cells go to different fate In our body, there are many other types of neurons The researchers hope that this method can also effectively find out the key "switches" that determine the structure and function of other neurons, providing insights for understanding the wonder of life