Fig. 2: MDNCs from controls (CTL) versus patients with schizophrenia (SCZ). | Molecular Psychiatry

Fig. 2: MDNCs from controls (CTL) versus patients with schizophrenia (SCZ).

From: Dopamine-induced pruning in monocyte-derived-neuronal-like cells (MDNCs) from patients with schizophrenia

Fig. 2: MDNCs from controls (CTL) versus patients with schizophrenia (SCZ).

A Representative light microscopy photographs of the four different morphologies characterized during transdifferentiation: rounded cells (RC), standard macrophages (SM), fibroblastic shape (FS) and uncharacterized (UC) (20x original magnification). Scale bar = 20 µm. B Bar graphs showing variations between controls and patients with schizophrenia in the percentage of each of the four cell morphologies on day 4, 7, 10 and 13 of transdifferentiation. Repeated ANOVAs based on the mixed model framework were performed to examine group differences for each day. Data are given as mean ± SEM. Cells from 12 CTL and 13 SCZ were characterized for day 4, 7 & 10 and 5 CTL and 11 SCZ for day 13. Cells characterized on day 4, CTL n = 8437, SCZ n = 8204; on day 7, CTL n = 7783, SCZ n = 7609; on day 10, CTL n = 7125, SCZ n = 6830; and on day 13, CTL n = 2475, SCZ n = 5342. *P = or < 0.05. C Bar graphs contrasting the percentage of differentiated cells between CTL, SCZ and only medicated patients (MED). CTL, 12.7 ± 1.3%; SCZ, 16.7 ± 1.3%; P = 0.04; MED, 17.4 ± 1.4%; P = 0.027. Differentiation was obtained via cell phenotype. To determine differences between groups, multilevel mixed models to account for correlations of repeated measures at subject level and sample level were used, followed by a two-sample t test. Data are given as mean ± SEM. Cells from 12 CTL and 13 SCZ (of which 11 are medicated “MED”) were included in the analysis. Characterized cells for CTL, n = 32791; SCZ n = 37281; and for MED n = 32986. *P = or < 0.05, **P < 0.03. D Dot plots contrasting relative fluorescence intensity (RFI) of CD14 in macrophages (MF) versus MDNCs from either CTL or SCZ. CD14 RFI was measured via flow cytometry. For CTL, MF, 140 ± 44; MDNCs, 49 ± 17; P = 0.03; for SCZ, MF, 154 ± 34.5; MDNCs, 110 ± 33.8; P = 0.25. Differences were assessed using the Mann–Whitney test. Data are given as mean ± SEM. Cells from 10 CTL and 11 SCZ were included in the analysis. *P = or < 0.05. E Dot plots contrasting the percentage of cells expressing high levels of nestin in MF versus MDNCs from either CTL or SCZ. Nestin expression was measured via flow cytometry. For CTL, MF, 5.6 ± 2%; MDNCs, 14.7 ± 5.3%; P = 0.4 and for SCZ, MF, 6.3 ± 2.6%; MDNCs, 19.2 ± 2.5%; P = 0.01. Differences were assessed using the Mann–Whitney test. Data are given as mean ± SEM. Cells from 2 CTL and 4 SCZ were included in the analysis. One CTL was tested twice by duplicate. *P = or < 0.05. F Bar graphs contrasting several structural parameters at baseline between CTL, SCZ and MED. Structural parameters include: Longest primary neurite (LPN) (CTL, 91 ± 2.6 µm; SCZ, 93.5 ± 2.4 µm; P = 0.49, MED, 94.5 ± 2.6 µm; P = 0.36); longest secondary neurite (LSN) (CTL, 15.8 ± 0.7 µm; SCZ, 18.4 ± 0.6 µm; P = 0.02, MED, 18.1 ± 0.7 µm; P = 0.04); number of primary neurites (CTL, 4.3 ± 0.09; SCZ, 4.6 ± 0.08; P = 0.04, MED, 4.6 ± 0.09; P = 0.01); number of secondary neurites (CTL, 5.1 ± 0.5; SCZ, 6.2 ± 0.4; P = 0.17, MED, 6.2 ± 0.5; P = 0.19) and total number of neurites (CTL, 8.8 ± 0.6; SCZ, 10.2 ± 0.6; P = 0.11, MED, 10.3 ± 0.6; P = 0.13). To determine differences between groups, multilevel mixed models to account for correlations of repeated measures at subject level and sample level were used, followed by a two-sample t test. Data are given as mean ± SEM. MDNCs from 12 CTL and 13 SCZ (of which 11 are medicated “MED”) were included in the analysis. MDNCs traced for CTL n = 3933; SCZ n = 6144; and MED n = 5601. *P = or < 0.05, **P < 0.03. G Bar graphs contrasting several structural parameters on day 20 versus day 21 from CTL, SCZ and MED. Structural parameters studied were; longest primary neurite (LPN), longest secondary neurite (LSN), number of primary neurites, number of secondary neurites and total number of neurites. Two-sample t-tests was used to determine differences between CTL vs. SCZ and CTL vs. MED after a mixed model analysis was performed to account for correlations of repeated measures within subjects. Data are given as mean ± SEM. MDNCs from 7 CTL and 11 SCZ (of which 10 are medicated “MED”) were included in the analysis. MDNCs traced for LSN for CTL, day 20 n = 1090 and day 21 n = 1091; for all other structural parameters; CTL, day 20 n = 1189 and day 21 n = 1213; for LSN for SCZ, day 20 n = 2062 and day 21 n = 2152; for all other structural parameters day 20 n = 2193 and day 21 n = 2254; for LSN for MED, day 20 n = 1985 and day 21 n = 2018; for all other structural parameters day 20 n = 2114 and day 21 n = 2118. *P = or < 0.05, **P < 0.03.

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