Fig. 6: Single-cell analysis uncovers SCDi-mediated changes to the cellular landscape of microglia. | Nature Communications

Fig. 6: Single-cell analysis uncovers SCDi-mediated changes to the cellular landscape of microglia.

From: Stearoyl-CoA Desaturase inhibition reverses immune, synaptic and cognitive impairments in an Alzheimer’s disease mouse model

Fig. 6

a tSNE plot showing the microglia population can be subclustered into seven microglial subtypes/activation states (subclusters 1–7). b Violin plots of top 4 DEGs used to define the microglia cluster (P2ry12, Tmem119, Slc2a5, Fcris) followed by the top 4 subcluster-specific DEGs. Subclusters were annotated on the basis of prior single-cell RNA sequencing studies and additional strategies as described in the sections “Results” and “Methods”: Resting/Homeostatic (RH1, RH2, subclusters 1,2), Transitioning (T(AR/AIR), subcluster 3), Transitioning (T(ASR), subcluster 4), Active Response (AR, subcluster 5), Active Interferon Response (AIR, subcluster 6), Active Synapse-associated Response (ASR, subcluster 7). c PAGA-tree trajectory inference and pseudotime analysis of the microglia cluster, showing microglia subclusters annotated as “Active” (AR, AIR, ASR) have increased pseudotime transition. d Violin plot of nCounts across all microglia subclusters, showing the microglia subclusters annotated as “Active” (AR, AIR, ASR) have higher numbers of unique molecular identifiers (UMI) than “Resting” microglia (RH1, RH2). e Percentages of total microglia found in each subcluster in each experimental group. f Activation scores for the AR/AIR and ASR lineages for each experimental group. Activation scores were calculated as the lineage-positive cells (“Transitional” + ”Active”) expressed as percentage of the resting cells (RH1 + RH2). 100% indicates an equal proportion of lineage-positive to resting cells. g Violin plots of showing relative expression of the top 6 SCDi-regulated genes (between 3xTg-D and 3xTg-S) across microglial subclusters. h, i Violin plots of expression levels of H2-D1 in the AR/AIR lineage (h) and ASR lineage (i) in each experimental group. Blue lines identify the average expression level. Legend of experimental groups in (e) applies to panels e, f, h, i. See Supplemental Figs. 6–8 and Supplemental Data Files 2, 3.

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