Barbar L, Jain T, Zimmer M, Kruglikov I, Sadick JS, Wang M, Kalpana K, Rose IV, Burstein SR, Rusielewicz T, Nijsure M, Guttenplan KA, di Domenico A, Croft G, Zhang B, Nobuta H, Hébert JM, Liddelow SA, Fossati V. CD49f Is a Novel Marker of Functional and Reactive Human iPSC-Derived Astrocytes. Neuron. 2020 Aug 5;107(3):436-453.e12. Epub 2020 Jun 1 PubMed.
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University of Rochester School of Medicine and Dentistry
The Neuron paper has done a nice job of characterizing CD49f as a marker of human astrocytes and shown evidence that it can be used to isolate astrocytes from hIPSC cultures that mimic many classic features of astrocytes, including support of neurons, glutamate clearance, and responsiveness to inflammatory stimuli. They go on to show in vitro that these cells take on A1-like characteristics after inflammatory stimuli and become neurotoxic. A strength of the work was reproducibility of observed phenotypes across multiple hIPSC cultures. Overall, this approach provides an additional and potentially quite useful tool for investigating the roles of human astrocytes in cell model systems and neurologic disease. I find very little to criticize in their approach, or thoroughness of study, though an evaluation of developmental CD49f expression would have been a nice touch.
View all comments by M. Kerry O'BanionUCL Institute of Neurology and The Francis Crick Institute
Astrocytes have increasingly recognized pathogenic roles in a range of neurodegenerative diseases. The ability to study enriched populations of human astrocytes is an important addition to our existing experimental repertoire. This study identifies a new marker to purify human induced pluripotent stem cell (hiPSC)-derived astrocytes and further demonstrates that these undergo deleterious reactive transformation in response to an established program of extrinsic pro-inflammatory cues.
Importantly, the induction of this deleterious reactive state led to the disruption of key astrocyte homeostatic functions (that would otherwise support juxtaposed neurons in vivo). Further studies might build upon this important work by addressing whether such astrocyte reactive changes are largely uniform or if they exhibit spatiotemporal heterogeneity within the nervous system and across different disease states. Such information may help us to understand the scope of therapeutically targeting astrocytes in a range of neurodegenerative diseases.
View all comments by Rickie PataniMake a Comment
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