MOESM1 of LIN28B is highly expressed in atypical teratoid/rhabdoid tumor (AT/RT) and suppressed through the restoration of SMARCB1

Additional file 1: Table S1. mRNA/miRNA expression after LIN28 knockdown

Additional file 2: of M1 macrophage recruitment correlates with worse outcome in SHH Medulloblastomas

Table S1. List of antibodies used for immunohistochemistry and immunofluorescence assay Table S2. Correlation between TAM and other prognostic factors estimated with a logistic regression in SHH MB. (DOCX 17 kb

Additional file 1: of M1 macrophage recruitment correlates with worse outcome in SHH Medulloblastomas

Figure S1. Macrophage recruitment in human tonsil FFPE tissue. Figure S2. Expression heatmap of 22 subgroup-specific signature genes in 48 study patients by the nanoString nCounter System. Figure S3. TAM recruitment and prognostic outcomes in the whole patient cohort. Figure S4. TAM recruitment and prognostic outcomes in SHH MB from Yonsei University. (PPTX 3883 kb

Correction: Human Adipose Tissue-Derived Mesenchymal Stem Cells Target Brain Tumor-Initiating Cells

<p>Correction: Human Adipose Tissue-Derived Mesenchymal Stem Cells Target Brain Tumor-Initiating Cells</p

Chemokine Ligand 5 (CCL5) Derived from Endothelial Colony-Forming Cells (ECFCs) Mediates Recruitment of Smooth Muscle Progenitor Cells (SPCs) toward Critical Vascular Locations in Moyamoya Disease

<div><p>The etiology and pathogenesis of moyamoya disease (MMD) are still obscure. Previous studies indicated that angiogenic chemokines may play an important role in the pathogenesis of the disease. Recently, it was discovered that peripheral blood-derived endothelial colony-forming cells (ECFCs) and smooth muscle progenitor cells (SPCs) have defective functions in MMD patients. Therefore, the interaction of ECFCs and SPCs, the precursors of two crucial cellular components of vascular walls, with some paracrine molecules is an intriguing subject. In this study, co-culture of ECFCs and SPCs from MMD patients and healthy normal subjects revealed that MMD ECFCs, not SPCs, are responsible for the defective functions of both ECFCs and SPCs. Enhanced migration of SPCs toward MMD ECFCs supported the role for some chemokines secreted by MMD ECFCs. Expression arrays of MMD and normal ECFCs suggested that several candidate cytokines differentially produced by MMD ECFCs. We selected chemokine (C-X-C motif) ligand 6 (CXCR6), interleukin-8 (IL8), chemokine (C-C motif) ligand 2 (CCL2), and CCL5 for study, based on the relatively higher expression of these ligands in MMD ECFCs and their cognate receptors in MMD SPCs. Migration assays showed that only CCL5 significantly augmented the migration activities of SPCs toward ECFCs. Treatment with siRNA for the CCL5 receptor (CCR5) abrogated the effect, confirming that CCL5 is responsible for the interaction of MMD ECFCs and SPCs. These data indicate that ECFCs, not SPCs, are the major players in MMD pathogenesis and that the chemokine CCL5 mediates the interactions. It can be hypothesized that in MMD patients, defective ECFCs direct aberrant SPC recruitment to critical vascular locations through the action of CCL5.</p></div

Trans-well migration assays (original magnification ×200).

<p>Migration of SPCs is enhanced when MMD ECFCs are placed in the bottom well (n = 4 for each group). The cell intensity value for combination of normal SPCs and MMD ECFCs is 166 ± 58.9% of control (combination of normal SPCs and normal ECFCs) (p = 0.029). The cell intensity for combination of MMD SPCs and MMD ECFCs are 539 ± 161.8% of control (p<0.001).</p

Induced cytokine levels in the BTICs after co-cultured with HFF1 or hAT-MSCs (pg/ml)^*.

<p>BTICs: brain tumor initiating cells, HFF1: human foreskin fibroblast, hAT-MSCs: human adipose-derived mesenchymal stem cells, AT/RT: atypical teratoid rhabdoid tumor, MCP-1: monocyte chemoattractant protein 1, SDF-1: stromal cell-derived factor 1, RANTES: regulated on activation, normal T cell expressed and secreted, IL-6: interleukin-6 ligand, IL-8: interleukin-8, IGF-1: insulin-like growth factor 1ligand, PDGF-bb: platelet-derived growth factor, VEGF: vascular endothelial growth factor, Ang-1: angiopoietin1</p><p>*[induced cytokine level in the BTICs with HFF1] = [total cytokine level in the BTICs with HFF1]-[cytokine level in the HFF1 only]</p><p>[induced cytokine level in the BTICs with hAT-MSCs] = [total cytokine level in the BTICs with hAT-MSCs]-[cytokine level in the hAT-MSCs only]</p><p>Induced cytokine levels in the BTICs after co-cultured with HFF1 or hAT-MSCs (pg/ml)^{<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0129292#t001fn002" target="_blank">*</a>}.</p

In vitro tube formation assays (original magnification ×100).

<p>(A and B) MMD ECFCs (green colored) make fewer tubes per unit area than normal ECFCs (n = 6, 11.9 ± 4.0% of control; p<0.001). MMD SPCs (red colored) also make less number of tubes (n = 6, 51.8 ± 21.5% of control; p<0.001). (C) The tube walls made by MMD ECFCs are thinner (n = 5, 14.4% of control; p< 0.001), but the tube walls composed of MMD SPCs are thicker than those of controls (n = 5, 763.4% of control; p<0.001) (*p<0.05, **p<0.01, ***p<0.001).</p

mRNA expression of cyto-chemokine receptors in human adipose tissue-derived mesenchymal stem cells (hAT-MSCs) after co-culture with brain tumor-initiating cells (BTICs).

<p>Real-time Quantitative Polymerase Chain Reaction (RT-qPCR) analysis of cyto-chemokine receptors after co-culture of (A) medulloblastoma-BTICs, (B) atypical teratoid/rhabdoid tumors (AT/RT)-BTICs and (C) glioblastoma-BTICs. The mRNA level of each cytokine receptor was normalized to the level of GAPDH. All data are representative of three independent experiments, and each value represents the mean ± SD. *Significant difference from control (P < 0.05).</p

Differentially expressed chemokines in MMD ECFCs.

<p>(A) Expression of various chemokines are compared between normal ECFCs (n = 4) and MMD ECFCs (n = 7). (B) KEGG pathway enrichment analysis; upregulated genes are involved in chemokine signaling pathway. (C) Four most-up-regulated chemokines in MMD ECFCs are selected for further analysis. (D) Confirmation of mRNA expression of select gene in ECFCs by RTq-PCR (n = 4 for each group). Significantly higher levels of CLCL6, IL8, and CCL5 mRNA are expressed in MMD-ECFCs (CXCL6, p = 0.038; IL8, p = 0.021; CCL2 p = 0.239; CCL5, p = 0.008).</p