The potential changes in molecular expression that can be undergone by reactive astrocytes is now being revealed as remarkably broad and heterogeneous across disorders and tissue regions, and fluid over time during disorders [23, 34, 50, 55–61]. For example, reactive astrocytes associated with stroke [50], LPS injection [50], traumatic brain injury [57], autoimmune disease (e.g. the experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis (MS)/MS) [17, 61], or different neurodegenerative disease models from mice and/or humans [58, 60, 62, 63], all exhibit transcriptome changes that vary substantially both in the number and types of genes whose expression change. Significant differences in transcriptome changes can also be observed (i) at different stages during the same disorder, for example at different times after stroke [50] or autoimmune attack (EAE) [61], and (ii) among different cohorts of locally intermingled reactive astrocytes in the same tissue samples evaluated by single cell or single nuclei RNA profiling [61, 63]. Notably, in many of the above cases, transcriptome differences appear to occur among reactive astrocytes that do not exhibit obvious differences in other features such as
