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Supplemental Table 1: SOX2 qPCR Array ID Gene Symbol Description Assay ID 1 CD44 CD44 antigen (homing function and Indian blood group system) Hs00174139_m1 2 AQP4 aquaporin 4 Hs00242341_m1 3 GFAP glial fibrillary acidic protein Hs00157674_m1 4 ELAVL4 HuD Hs00222634_m1 5 CD68 CD68 antigen Hs00154355_m1 6 ASCL1 MASH1 Hs00269932_m1 7 PROM1 CD133 Hs01009257_m1 8 CD24 CD24A Hs00273561_s1 9 HES1 hairy and enhancer of split 1 Hs00172878_m1 10 PAX6 paired box gene 6 Hs01088112_m1 11 MSI1 musashi homolog 1 Hs00159291_m1 12 NES Nestin Hs00707120_s1 13 SOX2 SRY (sex determining region Y)-box 2 Hs01053049_s1 14 OLIG2 oligodendrocyte lineage transcription factor 2 Hs00377820_m1 15 SOX10 DOM; WS4; MGC15649 Hs00366918_m1 16 PDGFRA platelet-derived growth factor receptor, alpha polypeptide Hs00998026_m1 17 CSPG4 NG2 Hs00426981_m1 18 ST8SIA1 A2B5, SIAT8A, G3 synthase Hs00268157_m1 19 SLC1A3 GLAST Hs00188193_m1 20 FABP7 brain fatty acid binding protein 7, BLBP (Brain lipid-binding protein) Hs00361426_m1 21 TERT hTERT, Telomerase reverse transcriptase Hs00162669_m1 22 P2RY5 purinergic receptor P2Y Hs00271758_s1 23 ADORA2B adenosine A2b receptor Hs00386497_m1 24 NOG Noggin Hs00271352_s1 25 BAMBI NMA Hs00180818_m1 26 TTYH1 tweety homolog 1 (Drosophila) Hs00221061_m1 27 CD99 CD99 molecule Hs00242853_m1 28 CD58 CD58 molecule Hs00156385_m1 29 CD109 CD109 molecule Hs00370347_m1 30 CD164 sialomucin Hs00985280_m1 31 Gli3 Zinc finger protein GLI3 Hs00609233_m1 32 CDH6 cadherin 6, type 2, K-cadherin (fetal kidney) Hs00191832_m1 33 VEGF vascular endothelial growth factor Hs00900055_m1 34 LIFR leukemia inhibitory factor receptor; CD118 Hs00158730_m1 35 IL6ST interleukin 6 signal transducer (gp130, oncostatin M receptor); CD130 Hs00174360_m1 36 CEBPB CCAAT/enhancer binding protein (C/EBP), beta, Nuclear factor NF-IL6 Hs00270923_s1 37 NMI N-myc (and STAT) interactor Hs00190768_m1 38 SPP1 osteopontin Hs00167093_m1 39 TNFSF10 tumor necrosis factor (ligand) superfamily, member 10 Hs00234356_m1 40 TNFSF13B tumor necrosis factor (ligand) superfamily, member 13b Hs00198106_m1 41 GDF15 growth differentiation factor 15 Hs00171132_m1 42 SHC1 SHC (Src homology 2 domain containing) transforming protein 1 Hs00427539_m1 43 EDG2 endothelial differentiation, lysophosphatidic acid G-protein-coupled receptor, 2 Hs00173500_m1 44 HES5 hairy and enhancer of split 5 (Drosophila) Hs01387463_g1 45 NOTCH2 Notch homolog 2 (Drosophila) Hs01050720_mH 46 JAG1 jagged1 Hs00164982_m1 47 NOTCH1 Notch homolog 1 Hs01062014_m1 48 NOTCH3 Notch homolog 3 (Drosophila) Hs01128541_m1 49 Hey1 HARP Hs00232618_m1 50 NEUROG1 neurogenin 1, NGN1 Hs01029249_s1 51 NEUROG2 neurogenin 2, NGN2 Hs00702774_s1 52 DLL1 delta-like 1 (Drosophila) Hs00194509_m1 53 NEUROD2 neurogenic differentiation 2 Hs00272055_s1 54 NEUROD1 neurogenic differentiation 1 Hs00159598_m1 55 NUMB numb homolog (Drosophila) Hs01105433_m1 56 HAP1 huntingtin-associated protein 1 (neuroan 1) Hs00171598_m1 57 SOX4 SRY (sex determining region Y)-box 4 Hs00268388_s1 58 ZIC1 Zic family member 1 (odd-paired homolog, Drosophila) Hs00602749_m1 59 WEE1 WEE1 homolog, WEE1A Hs00268721_m1 60 RREB1 ras responsive element binding protein 1 Hs00366111_m1 61 WWTR1 WW domain containing transcription regulator 1 (TAZ) Hs00210007_m1 62 DACH1 dachshund homolog 1 (Drosophila) Hs00189301_m1 63 YAP1 Yes-associated protein 1, 65kDa Hs00371735_m1 64 SALL1 sal-like 1 (Drosophila) Hs00231307_m1 65 ELAVL1 Hu antigen R Hs00171309_m1 66 BTG2 BTG family, member 2; NGF-inducible anti-proliferative protein PC3, Hs00198887_m1 67 LMCD1 LIM and cysteine-rich domains 1 Hs00205871_m1 68 FGF2 basic fibroblast growth factor Hs00266645_m1 69 EGF epidermal growth factor (beta-urogastrone) Hs00153181_m1 70 NPY2R neuropeptide Y receptor Y2 Hs00168567_m1 71 WNT5A wingless-type MMTV integration site family, member 5A Hs00998537_m1 72 DAAM2 dishevelled associated activator of morphogenesis 2 Hs00322497_m1 73 LY96 lymphocyte antigen 96 Hs00209771_m1 74 AGTR1 angiotensin II receptor, type 1 Hs00258937_m1 75 FAS Fas (TNF receptor superfamily, member 6); CD95 Hs00163653_m1 76 MET met proto-oncogene (hepatocyte growth factor receptor) Hs00179845_m1 77 IL13RA2 interleukin 13 receptor, alpha 2 Hs00152924_m1 78 ITGA2 integrin, alpha 2 (CD49B, alpha 2 subunit of VLA-2 receptor) Hs00158127_m1 79 TLR3 toll-like receptor 3; CD283 antigen Hs00152933_m1 80 TLR4 toll-like receptor 4; CD284 Hs00152939_m1 81 TNFRSF10D tumor necrosis factor receptor superfamily, member 10d;CD264, TRAILR4 Hs00388742_m1 82 TNFRSF10A tumor necrosis factor receptor superfamily, member 10a; CD261, TRAILR-1 Hs00269492_m1 83 TNFRSF19 tumor necrosis factor receptor superfamily, member 19; TRADE, TROY Hs00218634_m1 84 EPHA2 ephrin receptor EPH receptor A2 Hs00171656_m1 85 PTPRG protein tyrosine phosphatase, receptor type, G Hs00177193_m1 86 RGS16 regulator of G-protein signalling 16 Hs00892674_m1 87 NGFR nerve growth factor receptor; p75(NTR), CD271 Hs00609976_m1 88 NRP2 neuropilin 2; NPN2 Hs00187290_m1 89 PTPRZ1 RPTPzeta / phosphocan Hs00267839_m1 90 ENPP2 ectonucleotide pyrophosphatase/phosphodiesterase2 (autotaxin) Hs00905125_m1 91 FZD8 frizzled homolog 8 (Drosophila) Hs00259040_s1 92 FZD10 frizzled homolog 10 (Drosophila) Hs00273077_s1 93 FZD6 frizzled homolog 6 (Drosophila) Hs00171574_m1 94 DKK3 dickkopf homolog 3 (Xenopus laevis) Hs00247426_m1 95 DKK1 dickkopf 1 Hs00183740_m1 Type Symbol Description GeneID Ratio P‐value Ligand GPNMB glycoprotein (transmembrane) nmb 10457 24.01 4.40E‐03 S100A6 S100 calcium binding protein A6 6277 19.25 2.42E‐02 AGTR1 angiotensin II receptor, type 1 185 18.37 1.17E‐04 NOG Noggin 9241 16.59 3.75E‐03 ADM adrenomedullin 133 13.08 1.92E‐03 SPP1 osteopontin 6696 11.89 9.21E‐04 TNFSF10 tumor necrosis factor (ligand) superfamily, 8743 11.73 7.93E‐05 member 10 ANXA1 annexin A1 301 11.68 9.37E‐04 EGF epidermal growth factor (beta‐urogastrone) 1950 9.89 1.43E‐04 DKK3 dickkopf 3 27122 9.00 1.34E‐05 TNFSF13B tumor necrosis factor (ligand) superfamily, 10673 8.80 1.96E‐02 member 13b GDF15 growth differentiation factor 15 9518 8.48 5.98E‐03 CLU clusterin 1191 8.26 4.14E‐04 IL33 interleukin 33 90865 8.07 8.17E‐05 LAMA5 laminin, alpha 5 3911 7.24 5.81E‐03 SHC1 SHC (Src homology 2 domain containing) 6464 6.86 8.44E‐04 transforming protein 1 CMTM3 CKLF‐like MARVEL transmembrane domain 123920 6.51 1.07E‐04 containing 3 CD276 CD276 molecule 80381 6.19 4.77E‐04 LRDD leucine‐rich repeats and death domain 55367 5.95 9.99E‐04 containing FST follistatin 10468 5.46 9.63E‐05 TNFSF4 tumor necrosis factor (ligand) superfamily, 7292 5.45 1.12E‐02 member 4 CRH corticotropin releasing hormone 1392 5.34 2.40E‐02 EPHB4 EPH receptor B4 2050 5.33 1.84E‐03 TGFB2 transforming growth factor, beta 2 7042 5.32 5.03E‐03 GRN granulin 2896 5.20 3.90E‐04 PHIP pleckstrin homology domain interacting 55023 5.14 7.34E‐03 protein ITGA5 integrin, alpha 5 (fibronectin receptor, alpha 3678 5.01 2.04E‐03 polypeptide) ANGPTL2 angiopoietin‐like 2 23452 4.74 3.13E‐03 ADAM9 ADAM metallopeptidase domain 9 (meltrin 8754 4.36 1.64E‐03 gamma) APOL2 apolipoprotein L, 2 23780 4.35 2.51E‐03 MSN moesin 4478 4.34 8.69E‐03 TNC tenascin C 3371 4.27 5.52E‐04 SQSTM1 sequestosome 1 8878 4.26 5.71E‐04 SERPINE1 serpin peptidase inhibitor, clade E (nexin, 5054 4.18 1.36E‐03 plasminogen activator inhibitor type 1), member 1 ANGPTL1 angiopoietin‐like 1 9068 4.15 5.62E‐03 Receptor ELTD1 EGF, latrophilin and seven transmembrane 64123 33.92 3.94E‐03 domain containing 1 FZD10 frizzled 10 11211 33.20 9.80E‐06 LY96 lymphocyte antigen 96 23643 24.07 2.17E‐02 CFI complement factor I 3426 20.74 1.54E‐02 F2RL2 coagulation factor II (thrombin) receptor‐like 2151 18.93 1.48E‐03 2 Type Symbol Description GeneID Ratio P‐value TRPM3 transient receptor potential cation channel, 80036 18.92 4.68E‐05 subfamily M, member 3 CD44 CD44 antigen (homing function and Indian 960 16.38 1.77E‐05 blood group system) EDNRB endothelin receptor type B 1910 14.01 1.60E‐06 IL13RA2 interleukin 13 receptor, alpha 2 3598 13.99 1.02E‐03 MET met proto‐oncogene (hepatocyte growth 4233 13.00 2.61E‐03 factor receptor) ITGA2 integrin, alpha 2 (CD49B, alpha 2 subunit of 3673 12.95 2.57E‐04 VLA‐2 receptor) NPY2R neuropeptide Y receptor Y2 4887 12.64 5.37E‐04 TNFRSF10D tumor necrosis factor receptor superfamily, 8793 12.07 1.62E‐03 member 10d, decoy with truncated death domain LRP10 low density lipoprotein receptor‐related 26020 11.92 4.98E‐03 protein 10 GEM GTP binding protein overexpressed in 2669 11.84 5.07E‐05 skeletal muscle FAS tumor necrosis factor receptor superfamily, 355 10.84 7.30E‐06 member 6 TLR4 toll‐like receptor 4 7099 10.40 3.84E‐05 TLR3 toll‐like receptor 3 7098 10.30 1.22E‐04 FBN1 fibrillin 1 2200 9.64 9.73E‐05 WEE1 WEE1 homolog (S. pombe) 7465 9.38 3.63E‐04 DAAM2 dishevelled associated activator of 23500 8.83 2.92E‐04 morphogenesis 2 NOTCH2 Notch homolog 2 (Drosophila) 4853 8.53 4.67E‐03 GNG12 guanine nucleotide binding protein (G 55970 8.13 1.62E‐03 protein), gamma 12 BAMBI NMA 25805 8.06 2.44E‐03 HRH1 histamine receptor H1 3269 8.02 9.92E‐04 LGALS3BP lectin, galactoside‐binding, soluble, 3 binding 3959 7.85 7.49E‐05 protein LTBP1 latent transforming growth factor beta 4052 7.69 1.19E‐03 binding protein 1 HLA‐E major histocompatibility complex, class I, E 3133 7.24 2.86E‐04 TNFRSF19 tumor necrosis factor receptor superfamily, 55504 7.20 3.36E‐06 member 19 EPHA2 ephrin receptor EphA2 1969 7.17 6.05E‐05 CLIC1 chloride intracellular channel 1 1192 7.01 9.97E‐04 LIFR leukemia inhibitory factor receptor 3977 6.74 2.89E‐04 NGFR p75(NTR) 4804 6.42 2.17E‐03 IL6ST interleukin 6 signal transducer
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    + CD29 identifies IFN-γ–producing human CD8 T cells with an increased cytotoxic potential Benoît P. Nicoleta,b, Aurélie Guislaina,b, Floris P. J. van Alphenc, Raquel Gomez-Eerlandd, Ton N. M. Schumacherd, Maartje van den Biggelaarc,e, and Monika C. Wolkersa,b,1 aDepartment of Hematopoiesis, Sanquin Research, 1066 CX Amsterdam, The Netherlands; bLandsteiner Laboratory, Oncode Institute, Amsterdam University Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands; cDepartment of Research Facilities, Sanquin Research, 1066 CX Amsterdam, The Netherlands; dDivision of Molecular Oncology and Immunology, Oncode Institute, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands; and eDepartment of Molecular and Cellular Haemostasis, Sanquin Research, 1066 CX Amsterdam, The Netherlands Edited by Anjana Rao, La Jolla Institute for Allergy and Immunology, La Jolla, CA, and approved February 12, 2020 (received for review August 12, 2019) Cytotoxic CD8+ T cells can effectively kill target cells by producing therefore developed a protocol that allowed for efficient iso- cytokines, chemokines, and granzymes. Expression of these effector lation of RNA and protein from fluorescence-activated cell molecules is however highly divergent, and tools that identify and sorting (FACS)-sorted fixed T cells after intracellular cytokine + preselect CD8 T cells with a cytotoxic expression profile are lacking. staining. With this top-down approach, we performed an un- + Human CD8 T cells can be divided into IFN-γ– and IL-2–producing biased RNA-sequencing (RNA-seq) and mass spectrometry cells. Unbiased transcriptomics and proteomics analysis on cytokine- γ– – + + (MS) analyses on IFN- and IL-2 producing primary human producing fixed CD8 T cells revealed that IL-2 cells produce helper + + + CD8 Tcells.
  • Ck1δ Over-Expressing Mice Display ADHD-Like Behaviors, Frontostriatal Neuronal Abnormalities and Altered Expressions of ADHD-Candidate Genes

    Ck1δ Over-Expressing Mice Display ADHD-Like Behaviors, Frontostriatal Neuronal Abnormalities and Altered Expressions of ADHD-Candidate Genes

    Molecular Psychiatry (2020) 25:3322–3336 https://doi.org/10.1038/s41380-018-0233-z ARTICLE CK1δ over-expressing mice display ADHD-like behaviors, frontostriatal neuronal abnormalities and altered expressions of ADHD-candidate genes 1 1 1 2 1 1 1 Mingming Zhou ● Jodi Gresack ● Jia Cheng ● Kunihiro Uryu ● Lars Brichta ● Paul Greengard ● Marc Flajolet Received: 8 November 2017 / Revised: 4 July 2018 / Accepted: 18 July 2018 / Published online: 19 October 2018 © Springer Nature Limited 2018 Abstract The cognitive mechanisms underlying attention-deficit hyperactivity disorder (ADHD), a highly heritable disorder with an array of candidate genes and unclear genetic architecture, remain poorly understood. We previously demonstrated that mice overexpressing CK1δ (CK1δ OE) in the forebrain show hyperactivity and ADHD-like pharmacological responses to D- amphetamine. Here, we demonstrate that CK1δ OE mice exhibit impaired visual attention and a lack of D-amphetamine- induced place preference, indicating a disruption of the dopamine-dependent reward pathway. We also demonstrate the presence of abnormalities in the frontostriatal circuitry, differences in synaptic ultra-structures by electron microscopy, as 1234567890();,: 1234567890();,: well as electrophysiological perturbations of both glutamatergic and GABAergic transmission, as observed by altered frequency and amplitude of mEPSCs and mIPSCs. Furthermore, gene expression profiling by next-generation sequencing alone, or in combination with bacTRAP technology to study specifically Drd1a versus Drd2 medium spiny neurons, revealed that developmental CK1δ OE alters transcriptional homeostasis in the striatum, including specific alterations in Drd1a versus Drd2 neurons. These results led us to perform a fine molecular characterization of targeted gene networks and pathway analysis. Importantly, a large fraction of 92 genes identified by GWAS studies as associated with ADHD in humans are significantly altered in our mouse model.
  • The Caenorhabditis Elegans Excretory System: a Model for Tubulogenesis, Cell Fate Specification, and Plasticity

    The Caenorhabditis Elegans Excretory System: a Model for Tubulogenesis, Cell Fate Specification, and Plasticity

    | WORMBOOK CELL AND ORGANELLE BIOLOGY The Caenorhabditis elegans Excretory System: A Model for Tubulogenesis, Cell Fate Specification, and Plasticity Meera V. Sundaram*,1 and Matthew Buechner† *Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104 and †Department of Molecular Biosciences, University of Kansas, Lawrence, Kansas 66045 ABSTRACT The excretory system of the nematode Caenorhabditis elegans is a superb model of tubular organogenesis involving a minimum of cells. The system consists of just three unicellular tubes (canal, duct, and pore), a secretory gland, and two associated neurons. Just as in more complex organs, cells of the excretory system must first adopt specific identities and then coordinate diverse processes to form tubes of appropriate topology, shape, connectivity, and physiological function. The unicellular topology of excretory tubes, their varied and sometimes complex shapes, and the dynamic reprogramming of cell identity and remodeling of tube connec- tivity that occur during larval development are particularly fascinating features of this organ. The physiological roles of the excretory system in osmoregulation and other aspects of the animal’s life cycle are only beginning to be explored. The cellular mechanisms and molecular pathways used to build and shape excretory tubes appear similar to those used in both unicellular and multicellular tubes in more complex organs, such as the vertebrate vascular system and kidney, making this simple organ system a