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Chunk #4 — Concepts of cell subtypes and states

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Astrocyte Reactivity: Subtypes, States, and Functions in CNS Innate Immunity.
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Advances in RNA sequencing and proteomics are enabling detailed assessment of molecular expression differences among cells. Nevertheless, it should be emphasized that meaningful definitions of differences in reactive astrocyte subtypes or states cannot be based solely on differences in molecular expression, but should be based on composite pictures that also include information about cell morphology, proliferation, molecular expression, functions, and cellular interactions. From a technical perspective it is also noteworthy that astrocytes are exquisitely sensitive to being isolated and rapidly undergo molecular changes associated with reactivity. If not controlled for, technically-induced artifactual changes can markedly skew or confound interpretation of molecular expression data. Here, with these points in mind, we refer to different reactive astrocyte subtypes as cells with permanent fundamental differences in the aforementioned composite ‘pictures’. In contrast, we refer to differences in astrocyte reactivity states as temporary changes in molecular expression and function that do not alter basic cell features and can progressively change or be reversible over time. Comparable examples among neurons would be that of hippocampal pyramidal neurons and cerebellar Purkinje neurons, representing distinct neuronal subtypes,