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               ·492 ·                            南 京    医 科 大 学 学         报                        2025年4月


              A


                        Tissue   Magnetic
                      dissociation  beads           Cell sorting     Elution                          1     10
                                                                                                       Nucleotide
                                   co⁃
                                 incubation
                                                                                              RNA sequencing


              B                                   C
                        Group                                          Metalion binding
                         3M⁃HD                                           DNA binding
                 (×10 )  3M⁃WT
                     4
                                                                     Extracellular region
                     8                                                                                Count
                                                   Regulation of transcription by RNA polymerasell      10
                                                           Multicellular organism development           20
                                                                           Proteolysis                  30
                                                                Protein⁃containing complex            -lg(P value)
                   (8.9%)  4                            Monoalomicion transmembrane transport           3.0
                                                            Protein heterodimerization activity
                                                                                                        2.5
                                                                    Neuron differentiation
                                                                                                        2.0
                   Dim2                                         Protein homooligomerization             1.5
                                                           Establishment of localization in cell
                                                                       Heparin binding
                    -4
                                                             High⁃density lipoprotein partide
                                                                          Stereocllium
                                                                                       10    20    30
                                                     5
                        -2    -1    0     1     2(×10 )                                   Count
                                Dim1(81.9%)
              D                                             E
                                              Group                  Extracellular region
                                               Down(122)             Extracellular space
                 4
                                               Non(17 595)        Monoatomicion transport
                                               Up(197)               Calciumion binding               Count
                value)  3                                     Basolateral plasma membrane               5 10
                                                                   Inflammatory response
                                                                                                        15
                (P  2                                        Response to lipopclysaccharide           -lg(P value)
                                                                  Postsynaptic membrane
                -lg                                               Epidermis development
                 1                                                       Synaptic cleft                 5
                                                                                                        4
                                                                  Receptor ligand activity
                                                                                                        3
                                                                    Spermidine transport
                 0                                                                                      2
                                                            Maintenance of synapse structure
                  -10    -5     0     5     10                  Atriated muscle contraction
                          log2 (Fold change)        Spermidine transmembrane transporter activity
                                                                                      5    10    15
                                                                                          Count
                    F
                                                                                                  Group
                                                                                                   HD
                                                                                                   WT
                                                                                                  Expression
                                                                                                   2
                                                                                                   1
                                                                                                   0
                                                                                                   -1
                                                                                                   -2
                                                                       C2
                               Adam18  Ascl2  Trim71  Six4  Tdrd9  Tdrd1  Tssk4  Satb2  Dppa5a  Fezf1  Lmx1a  Tll1  Ntf5  Htr3a  Artn  Cbln1  Cbln3  Reg3b  Ctsw  Drd2  Cxcl13  Fst  S100a14  Kcnj4  Napsa  Sfrp2  Cga  Tac1  Msr1

                 A:Schematic diagram of astrocyte isolation from mice brain. B:PCA analysis of 3⁃month⁃old mice in the HD group and WT group. C:The volcano
              map represent the differential gene expressions. D:GO functional enrichment analysis of up⁃regulated DEGs. E:GO functional enrichment analysis of
              down⁃regulated DEGs. F:The heatmap of synapse⁃related DEGs.
                                          图2  3月龄HD小鼠星形胶质细胞转录组学差异分析
                               Figure 2  Differential transcriptome analysis of astrocytes in 3⁃month⁃old HD mice
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