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. 2022 Jun 23;17(7):1650–1665. doi: 10.1016/j.stemcr.2022.05.019

Figure 2.

Figure 2

MiR-139-5p is downregulated in ALS MN

(A) Principal-component analysis (PCA) of 844 miRNAs in FUS H517Q/H517Q, FUS H517Q/+ and healthy MN harvested at day 30. N = 2 independent differentiations.

(B) Volcano plot of differentially expressed miRs in H517Q/H517Q versus healthy MNs (left panel) and H517Q/+ versus healthy MNs (right panel). MiR-139 is shown as a triangle (arrow).

(C) Heatmap of miRs identified as differentially expressed in at least 3 ALS datasets out of 6 analyzed. Red indicates upregulation, while blue indicates downregulation. Only miR-139 was commonly downregulated across all datasets (orange rectangle). sALS_spinalcord: postmortem cervical and thoracic spinal cord tissue from ALS patients versus healthy controls (Figueroa-Romero et al., 2016), sALS_LCM_MN: MNs enriched by laser capture microdissection of lumbar spinal cord tissue from ALS patients versus healthy controls (Emde et al., 2015). sALS_ventralhorn: lumbar ventral horn tissue of sporadic ALS versus non-degeneration controls (Reichenstein et al., 2019).

(D) Quantitative RT-PCR (qRT-PCR) confirmation of miR-139-5p downregulation in FUS H517Q MNs. N = 3–5 independent differentiations.

(E) Expression analysis of miR-139-5p over the time course of MN differentiation from healthy iPSCs (day 0). MiR-139-5p levels increase throughout MN differentiation and maturation. N = 3.

(F) MiR-139-5p expression assayed in spinal MN, V2a, and V3 interneurons. CPM indicates counts per million. RNA-seq data were obtained from Amin et al. (2015). Error bars indicate SEMs. ∗∗p <0.01 by Student’s t test.