When it comes to brain function, neurons get a lot of the glory. But healthy brains depend on the cooperation of many kinds of cells. The most abundant of the brain\u2019s non-neuronal cells are astrocytes, star-shaped cells with a lot of responsibilities. Astrocytes help shape neural circuits, participate in information processing, and provide nutrient and metabolic support to neurons. Individual cells can take on new roles throughout their lifetimes, and at any given time, the astrocytes in one part of the brain will look and behave differently than the astrocytes somewhere else.<\/p>\n
After an extensive analysis by researchers at MIT, neuroscientists now have an atlas detailing astrocytes\u2019 dynamic diversity. Its maps depict the regional specialization of astrocytes across the brains of both mice and marmosets \u2014 two powerful models for neuroscience research \u2014 and show how their populations shift as brains develop, mature, and age.\u00a0<\/p>\n
The open-access study, reported in the Nov. 20 issue of the journal Neuron<\/a>, was led by Guoping Feng<\/a>, the James W. (1963) and Patricia T. Poitras Professor of Brain and Cognitive Sciences at MIT. This work was supported by the Hock E. Tan and K. Lisa Yang Center for Autism Research<\/a>, part of the Yang Tan Collective<\/a> at MIT, and the National Institutes of Health\u2019s BRAIN Initiative.<\/p>\n \u201cIt\u2019s really important for us to pay attention to non-neuronal cells\u2019 role in health and disease,\u201d says Feng, who is also the associate director of the McGovern Institute for Brain Research and the director of the Hock E. Tan and K. Lisa Yang Center for Autism Research at MIT. And indeed, these cells \u2014 once seen as mere supporting players \u2014 have gained more of the spotlight in recent years. Astrocytes are known to play vital roles in the brain\u2019s development and function, and their dysfunction seems to contribute to many psychiatric disorders and neurodegenerative diseases. \u201cBut compared to neurons, we know a lot less \u2014 especially during development,\u201d Feng adds.<\/p>\n Probing the unknown<\/p>\n Feng and Margaret Schroeder, a former graduate student in his lab, thought it was important to understand astrocyte diversity across three axes: space, time, and species. They knew from earlier work in the lab, done in collaboration with Steve McCarroll\u2019s lab at Harvard University and led by Fenna Krienen in his group, that in adult animals, different parts of the brain have distinctive sets of astrocytes.<\/p>\n \u201cThe natural question was, how early in development do we think this regional patterning of astrocytes starts?\u201d Schroeder says.<\/p>\n To find out, she and her colleagues collected brain cells from mice and marmosets at six stages of life, spanning embryonic development to old age. For each animal, they sampled cells from four different brain regions: the prefrontal cortex, the motor cortex, the striatum, and the thalamus.<\/p>\n Then, working with Krienen, who is now an assistant professor at Princeton University, they analyzed the molecular contents of those cells, creating a profile of genetic activity for each one. That profile was based on the mRNA copies of genes found inside the cell, which are known collectively as the cell\u2019s transcriptome. Determining which genes a cell is using, and how active those genes are, gives researchers insight into a cell\u2019s function and is one way of defining its identity.<\/p>\n Dynamic diversity<\/p>\n After assessing the transcriptomes of about 1.4 million brain cells, the group focused in on the astrocytes, analyzing and comparing their patterns of gene expression. At every life stage, from before birth to old age, the team found regional specialization: astrocytes from different brain regions had similar patterns of gene\u00a0expression, which\u00a0were distinct from those of astrocytes in other brain regions.<\/p>\n