| Autor: |
Krawczyk, Mitchell C., Haney, Jillian R., Pan, Lin, Caneda, Christine, Khankan, Rana R., Reyes, Samuel D., Chang, Julia W., Morselli, Marco, Vinters, Harry V., Wang, Anthony C., Cobos, Inma, Gandal, Michael J., Bergsneider, Marvin, Kim, Won, Liau, Linda M., Yong, William, Jalali, Ali, Deneen, Benjamin, Grant, Gerald A., Mathern, Gary W. |
| Předmět: |
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| Zdroj: |
Journal of Neuroscience; 2/23/2022, Vol. 42 Issue 8, p1587-1603, 17p |
| Abstrakt: |
Astrocytes are critical for the development and function of synapses. There are notable species differences between human astrocytes and commonly used animal models. Yet, it is unclear whether astrocytic genes involved in synaptic function are stable or exhibit dynamic changes associated with disease states and age in humans, which is a barrier in understanding human astrocyte biology and its potential involvement in neurologic diseases. To better understand the properties of human astrocytes, we acutely purified astro- cytes from the cerebral cortices of over 40 humans across various ages, sexes, and disease states. We performed RNA sequencing to generate transcriptomic profiles of these astrocytes and identified genes associated with these biological variables. We found that human astrocytes in tumor-surrounding regions downregulate genes involved in synaptic function and sensing of signals in the micro- environment, suggesting involvement of peritumor astrocytes in tumor-associated neural circuit dysfunction. In aging, we also found downregulation of synaptic regulators and upregulation of markers of cytokine signaling, while in maturation we identified changes in ionic transport with implications for calcium signaling. In addition, we identified subtle sexual dimorphism in human cortical astrocytes, which has implications for observed sex differences across many neurologic disorders. Overall, genes involved in synaptic function exhibit dynamic changes in the peritumor microenvironment and aging. These data provide powerful new insights into human astrocyte biology in several biologically relevant states that will aid in generating novel testable hypotheses about homeostatic and reactive astrocytes in humans. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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