Astrocytes widely present in the central nervous system (CNS), they intimately contacts with synapses, blood vessels and other glial cells in normal brains [1]. Indeed, astrocytes play an important role in abnormal events in the CNS, including neurodegenerative and demyelinating diseases, epilepsy, trauma, ischemia, infection, and cancer [2]. In Alzheimer’s Disease (AD) and aging, disease-associated astrocytes (DAAs) were observed, which were termed as inflammation/A1 astrocyte signatures [3]. In glioblastoma, tumor-associated reactive astrocytes were found, which were termed as anti-inflammation/A2 astrocyte signatures [4]. In an early transcriptome study [5] and its follow-up [6–9] : for pan-reactive astrocytes, Lcn2, Steap4, S1pr3, Timp1, Hspb1, Cxcl10, Cd44, Osmr, Cp, Serpina3n, Aspg, Vim and Gfap are suitable as marker genes. For A1-reactive astrocytes, H2-T23, Serping1, H2-D1, Ggta1, Iigp1, Gbp2, Fbln5, Ugt1a1, Fkbp5, Psmb8, Srgn, Amigo2 and C3 are suitable as marker genes. For A2-reactive astrocytes, Clcf1, Tgm1, Ptx3, S100a10, Sphk1, Cd109, Ptgs2, Emp1, Slc10a6, Tm4sf1, B3gnt5 and Cd14 are suitable as marker genes. However, ScRNAseq and single-nucleus RNAseq (snRNAseq) studies of astrocytes in Huntington’s disease (HD) [10], AD [3, 11] and multiple sclerosis [12] mouse models and human brains do not clearly comply with A1–A2 profiles.
In this paper, by comparing FACS-bulk RNAseq and ScRNAseq data, based on the difference to determine that most of marker genes of A1 and A2 reactive astrocytes expressed in endothelial cells.