A Single-Cell Transcriptome Atlas of the Aging Drosophila Brain

Cell

Volumn 174, Issue 4, 2018, Pages 982-998.e20

  Davie, Kristofer ^a   Janssens, Jasper ^a   Koldere, Duygu ^a   De Waegeneer, Maxime ^a   Pech, Uli ^a   Kreft, Łukasz ^b   Aibar, Sara ^a   Makhzami, Samira ^a   Christiaens, Valerie ^a   Bravo González Blas, Carmen ^a   Poovathingal, Suresh ^a   Hulselmans, Gert ^a   Spanier, Katina I ^a   Moerman, Thomas ^a,c   Vanspauwen, Bram ^a   Geurs, Sarah ^a   Voet, Thierry ^a   Lammertyn, Jeroen ^a   Thienpont, Bernard ^a   Liu, Sha ^a   Konstantinides, Nikos ^d   Fiers, Mark ^a   Verstreken, Patrik ^a   Aerts, Stein ^a   more..

^a UNIVERSITY OF LEUVEN   (Belgium)

^b DEPARTMENT OF PLANT SYSTEMS BIOLOGY   (Belgium)

^c IMEC   (Belgium)

^d NEW YORK UNIVERSITY   (United States)

Author keywords

aging; brain; Drosophila; gene regulatory networks; mitochondria; neuronal subtypes; oxidative phosphorylation; single cell bioinformatics; single cell RNA seq

Indexed keywords

TRANSCRIPTOME; DROSOPHILA PROTEIN;

ADULT; AGING; ANIMAL CELL; ARTICLE; BRAIN MAPPING; CELL SELECTION; CONTROLLED STUDY; DROSOPHILA; ENERGY CONSUMPTION; GENE EXPRESSION; GENE REGULATORY NETWORK; GENETIC ANALYSIS; GENETIC VARIABILITY; GLIA CELL; LIFESPAN; MACHINE LEARNING; NERVE CELL; NONHUMAN; PREDICTION; PRIORITY JOURNAL; RNA ANALYSIS; SINGLE CELL ANALYSIS; VALIDATION PROCESS; ANIMAL; BRAIN; DROSOPHILA MELANOGASTER; FEMALE; GENE EXPRESSION PROFILING; GENETICS; MALE; METABOLISM; PHYSIOLOGY; PROCEDURES;

AGING; ANIMALS; BRAIN; DROSOPHILA MELANOGASTER; DROSOPHILA PROTEINS; FEMALE; GENE EXPRESSION PROFILING; GENE REGULATORY NETWORKS; MALE; SINGLE-CELL ANALYSIS; TRANSCRIPTOME;

EID: 85048501088     PISSN: 00928674     EISSN: 10974172     Source Type: Journal    
DOI: 10.1016/j.cell.2018.05.057     Document Type: Article

References (105)

1. Abruzzi, K.C., Zadina, A., Luo, W., Wiyanto, E., Rahman, R., Guo, F., Shafer, O., Rosbash, M., RNA-seq analysis of Drosophila clock and non-clock neurons reveals neuron-specific cycling and novel candidate neuropeptides. PLoS Genet., 13, 2017, e1006613.
2. Aibar, S., González-Blas, C.B., Moerman, T., Huynh-Thu, V.A., Imrichova, H., Hulselmans, G., Rambow, F., Marine, J.-C., Geurts, P., Aerts, J., et al. SCENIC: single-cell regulatory network inference and clustering. Nat. Methods 14 (2017), 1083–1086.
3. Allada, R., Chung, B.Y., Circadian organization of behavior and physiology in Drosophila. Annu. Rev. Physiol. 72 (2010), 605–624.
4. Angerer, P., Haghverdi, L., Büttner, M., Theis, F.J., Marr, C., Buettner, F., destiny: diffusion maps for large-scale single-cell data in R. Bioinformatics 32 (2016), 1241–1243.
5. Aronesty, E., ea-utils: Command-line tools for processing biological sequencing data. 2011, Expression Analysis, Durham, NC.
6. Awasaki, T., Saito, M., Sone, M., Suzuki, E., Sakai, R., Ito, K., Hama, C., The Drosophila trio plays an essential role in patterning of axons by regulating their directional extension. Neuron 26 (2000), 119–131.
7. Bainton, R.J., Tsai, L.T.-Y., Schwabe, T., DeSalvo, M., Gaul, U., Heberlein, U., moody encodes two GPCRs that regulate cocaine behaviors and blood-brain barrier permeability in Drosophila. Cell 123 (2005), 145–156.
8. Bernardo-Garcia, F.J., Fritsch, C., Sprecher, S.G., The transcription factor Glass links eye field specification with photoreceptor differentiation in Drosophila. Development 143 (2016), 1413–1423.
9. Boll, W., Noll, M., The Drosophila Pox neuro gene: control of male courtship behavior and fertility as revealed by a complete dissection of all enhancers. Development 129 (2002), 5667–5681.
10. Bou Dib, P., Gnägi, B., Daly, F., Sabado, V., Tas, D., Glauser, D.A., Meister, P., Nagoshi, E., A conserved role for p48 homologs in protecting dopaminergic neurons from oxidative stress. PLoS Genet., 10, 2014, e1004718.
11. Brogiolo, W., Stocker, H., Ikeya, T., Rintelen, F., Fernandez, R., Hafen, E., An evolutionarily conserved function of the Drosophila insulin receptor and insulin-like peptides in growth control. Curr. Biol. 11 (2001), 213–221.
12. Carlsson, M.A., Diesner, M., Schachtner, J., Nässel, D.R., Multiple neuropeptides in the Drosophila antennal lobe suggest complex modulatory circuits. J. Comp. Neurol. 518 (2010), 3359–3380.
13. Chen, R., Wu, X., Jiang, L., Zhang, Y., Single-cell RNA-seq reveals hypothalamic cell diversity. Cell Rep. 18 (2017), 3227–3241.
14. Chen, Z., Del Valle Rodriguez, A., Li, X., Erclik, T., Fernandes, V.M., Desplan, C., A unique class of neural progenitors in the Drosophila optic lobe generates both migrating neurons and glia. Cell Rep. 15 (2016), 774–786.
15. Couch, J.A., Chen, J., Rieff, H.I., Uri, E.M., Condron, B.G., robo2 and robo3 interact with eagle to regulate serotonergic neuron differentiation. Development 131 (2004), 997–1006.
16. Crocker, A., Guan, X.-J., Murphy, C.T., Murthy, M., Cell-type-specific transcriptome analysis in the Drosophila mushroom body reveals memory-related changes in gene expression. Cell Rep. 15 (2016), 1580–1596.
17. Croset, V., Treiber, C.D., Waddell, S., Cellular diversity in the Drosophila midbrain revealed by single-cell transcriptomics. eLife, 7, 2018, e34550.
18. DeSalvo, M.K., Hindle, S.J., Rusan, Z.M., Orng, S., Eddison, M., Halliwill, K., Bainton, R.J., The Drosophila surface glia transcriptome: evolutionary conserved blood-brain barrier processes. Front. Neurosci., 8, 2014, 346.
19. Diesner, M., Predel, R., Neupert, S., Neuropeptide mapping of dimmed cells of adult Drosophila brain. J. Am. Soc. Mass Spectrom. 29 (2018), 890–902.
20. Doherty, J., Logan, M.A., Taşdemir, O.E., Freeman, M.R., Ensheathing glia function as phagocytes in the adult Drosophila brain. J. Neurosci. 29 (2009), 4768–4781.
21. Dobin, A., Davis, C.A., Schlesinger, F., Drenkow, J., Zaleski, C., Jha, S., Batut, P., Chaisson, M., Gingeras, T.R., STAR: ultrafast universal TNA-seq aligner. Bioinformatics 29 (2013), 15–21.
22. Eden, E., Navon, R., Steinfeld, I., Lipson, D., Yakhini, Z., GOrilla: a tool for discovery and visualization of enriched GO terms in ranked gene lists. BMC Bioinformatics, 10, 2009, 48.
23. Erclik, T., Li, X., Courgeon, M., Bertet, C., Chen, Z., Baumert, R., Ng, J., Koo, C., Arain, U., Behnia, R., et al. Integration of temporal and spatial patterning generates neural diversity. Nature 541 (2017), 365–370.
24. Feng, J., Liu, T., Zhang, Y., Using MACS to Identify Peaks from ChIP-Seq Data. Curr Protoc Bioinformatics, 2011, 10.1002/0471250953.bi0214s34.
25. Ferree, A.W., Trudeau, K., Zik, E., Benador, I.Y., Twig, G., Gottlieb, R.A., Shirihai, O.S., MitoTimer probe reveals the impact of autophagy, fusion, and motility on subcellular distribution of young and old mitochondrial protein and on relative mitochondrial protein age. Autophagy 9 (2013), 1887–1896.
26. Goto, A., Kadowaki, T., Kitagawa, Y., Drosophila hemolectin gene is expressed in embryonic and larval hemocytes and its knock down causes bleeding defects. Dev. Biol. 264 (2003), 582–591.
27. Goto, A., Kumagai, T., Kumagai, C., Hirose, J., Narita, H., Mori, H., Kadowaki, T., Beck, K., Kitagawa, Y., A Drosophila haemocyte-specific protein, hemolectin, similar to human von Willebrand factor. Biochem J 359 (2001), 99–108.
28. Gramates, L.S., Marygold, S.J., Santos, G.D., Urbano, J.-M., Antonazzo, G., Matthews, B.B., Rey, A.J., Tabone, C.J., Crosby, M.A., Emmert, D.B., et al., the FlyBase Consortium. FlyBase at 25: looking to the future. Nucleic Acids Res. 45:D1 (2017), D663–D671.
29. Hadžić T., Park, D., Abruzzi, K.C., Yang, L., Trigg, J.S., Rohs, R., Rosbash, M., Taghert, P.H., Genome-wide features of neuroendocrine regulation in Drosophila by the basic helix-loop-helix transcription factor DIMMED. Nucleic Acids Res. 43 (2015), 2199–2215.
30. Hamanaka, Y., Meinertzhagen, I.A., Immunocytochemical localization of synaptic proteins to photoreceptor synapses of Drosophila melanogaster. J. Comp. Neurol. 518 (2010), 1133–1155.
31. Han, X., Wang, R., Zhou, Y., Fei, L., Sun, H., Lai, S., Saadatpour, A., Zhou, Z., Chen, H., Ye, F., et al. Mapping the Mouse Cell Atlas by Microwell-Seq. Cell 172 (2018), 1091–1107.e17.
32. Hasegawa, E., Kitada, Y., Kaido, M., Takayama, R., Awasaki, T., Tabata, T., Sato, M., Concentric zones, cell migration and neuronal circuits in the Drosophila visual center. Development 138 (2011), 983–993.
33. Hasegawa, E., Kaido, M., Takayama, R., Sato, M., Brain-specific-homeobox is required for the specification of neuronal types in the Drosophila optic lobe. Dev. Biol. 377 (2013), 90–99.
34. Hassan, B.A., Bermingham, N.A., He, Y., Sun, Y., Jan, Y.N., Zoghbi, H.Y., Bellen, H.J., atonal regulates neurite arborization but does not act as a proneural gene in the Drosophila brain. Neuron 25 (2000), 549–561.
35. Huynh-Thu, V.A., Irrthum, A., Wehenkel, L., Geurts, P., Inferring regulatory networks from expression data using tree-based methods. PLoS ONE, 5, 2010, e12776.
36. Imrichová H., Hulselmans, G., Atak, Z.K., Potier, D., Aerts, S., i-cisTarget 2015 update: generalized cis-regulatory enrichment analysis in human, mouse and fly. Nucleic Acids Res. 43 (2015), W57–W64.
37. Ito, M., Masuda, N., Shinomiya, K., Endo, K., Ito, K., Systematic analysis of neural projections reveals clonal composition of the Drosophila brain. Curr. Biol. 23 (2013), 644–655.
38. Jang, S., Nelson, J.C., Bend, E.G., Rodríguez-Laureano, L., Tueros, F.G., Cartagenova, L., Underwood, K., Jorgensen, E.M., Colón-Ramos, D.A., Glycolytic enzymes localize to synapses under energy stress to support synaptic function. Neuron 90 (2016), 278–291.
39. Janky, R., Verfaillie, A., Imrichová H., Van de Sande, B., Standaert, L., Christiaens, V., Hulselmans, G., Herten, K., Naval Sanchez, M., Potier, D., et al. iRegulon: from a gene list to a gene regulatory network using large motif and track collections. PLoS Comput. Biol., 10, 2014, e1003731.
40. Johard, H.A.D., Enell, L.E., Gustafsson, E., Trifilieff, P., Veenstra, J.A., Nässel, D.R., Intrinsic neurons of Drosophila mushroom bodies express short neuropeptide F: relations to extrinsic neurons expressing different neurotransmitters. J. Comp. Neurol. 507 (2008), 1479–1496.
41. Jones, E., Oliphant, T., and Peterson, P. (2001). SciPy: Open source scientific tools for Python. http://www.scipy.org/.
42. Kanehisa, M., Goto, S., KEGG: kyoto encyclopedia of genes and genomes. Nucleic Acids Res. 28 (2000), 27–30.
43. Karaiskos, N., Wahle, P., Alles, J., Boltengagen, A., Ayoub, S., Kipar, C., Kocks, C., Rajewsky, N., Zinzen, R.P., The Drosophila embryo at single-cell transcriptome resolution. Science 358 (2017), 194–199.
44. Karuppudurai, T., Lin, T.-Y., Ting, C.-Y., Pursley, R., Melnattur, K.V., Diao, F., White, B.H., Macpherson, L.J., Gallio, M., Pohida, T., Lee, C.H., A hard-wired glutamatergic circuit pools and relays UV signals to mediate spectral preference in Drosophila. Neuron 81 (2014), 603–615.
45. Klaes, A., Menne, T., Stollewerk, A., Scholz, H., Klämbt, C., The Ets transcription factors encoded by the Drosophila gene pointed direct glial cell differentiation in the embryonic CNS. Cell 78 (1994), 149–160.
46. Klarsfeld, A., Malpel, S., Michard-Vanhée, C., Picot, M., Chélot, E., Rouyer, F., Novel features of cryptochrome-mediated photoreception in the brain circadian clock of Drosophila. J. Neurosci. 24 (2004), 1468–1477.
47. Kolodziejczyk, A., Sun, X., Meinertzhagen, I.A., Nässel, D.R., Glutamate, GABA and acetylcholine signaling components in the lamina of the Drosophila visual system. PLoS ONE, 3, 2008, e2110.
48. Komiyama, T., Luo, L., Intrinsic control of precise dendritic targeting by an ensemble of transcription factors. Curr. Biol. 17 (2007), 278–285.
49. Komiyama, T., Johnson, W.A., Luo, L., Jefferis, G.S.X.E., From lineage to wiring specificity. POU domain transcription factors control precise connections of Drosophila olfactory projection neurons. Cell 112 (2003), 157–167.
50. Konstantinides, N., Kapuralin, K., Fadil, C., Barboza, L., Satija, R., Desplan, C., Phenotypic convergence: distinct transcription factors regulate common terminal features. Cell, 173, 2018, 10.1016/j.cell.2018.05.021.
51. Kremer, M.C., Jung, C., Batelli, S., Rubin, G.M., Gaul, U., The glia of the adult Drosophila nervous system. Glia 65 (2017), 606–638.
52. Kunst, M., Hughes, M.E., Raccuglia, D., Felix, M., Li, M., Barnett, G., Duah, J., Nitabach, M.N., Calcitonin gene-related peptide neurons mediate sleep-specific circadian output in Drosophila. Curr. Biol. 24 (2014), 2652–2664.
53. Kurtzer, G.M., Sochat, V., Bauer, M.W., Singularity: Scientific containers for mobility of compute. PLoS ONE, 12, 2017, e0177459.
54. Lake, B.B., Chen, S., Sos, B.C., Fan, J., Kaeser, G.E., Yung, Y.C., Duong, T.E., Gao, D., Chun, J., Kharchenko, P.V., Zhang, K., Integrative single-cell analysis of transcriptional and epigenetic states in the human adult brain. Nat. Biotechnol. 36 (2018), 70–80.
55. Laker, R.C., Xu, P., Ryall, K.A., Sujkowski, A., Kenwood, B.M., Chain, K.H., Zhang, M., Royal, M.A., Hoehn, K.L., Driscoll, M., et al. A novel MitoTimer reporter gene for mitochondrial content, structure, stress, and damage in vivo. J. Biol. Chem. 289 (2014), 12005–12015.
56. Li, H., Handsaker, B., Wysoker, A., Fennell, T., Ruan, J., Homer, N., Marth, G., Abecasis, G., Durbin, R., 1000 Genome Project Data Processing Subgroup. The sequence alignment/map format and SAMtools. Bioinformatics 25 (2009), 2078–2079.
57. Li, H., Horns, F., Wu, B., Xie, Q., Li, J., Li, T., Luginbuhl, D.J., Quake, S.R., Luo, L., Classifying Drosophila olfactory projection neuron subtypes by single-cell RNA sequencing. Cell 171 (2017), 1206–1220.e22.
58. Li, X., Erclik, T., Bertet, C., Chen, Z., Voutev, R., Venkatesh, S., Morante, J., Celik, A., Desplan, C., Temporal patterning of Drosophila medulla neuroblasts controls neural fates. Nature 498 (2013), 456–462.
59. Liao, Y., Smyth, G.K., Shi, W., featureCounts: an efficient general purpose program for assigning sequence reads to genomic features. Bioinformatics 30 (2014), 923–930.
60. Liu, Z., Yang, C.-P., Sugino, K., Fu, C.-C., Liu, L.-Y., Yao, X., Lee, L.P., Lee, T., Opposing intrinsic temporal gradients guide neural stem cell production of varied neuronal fates. Science 350 (2015), 317–320.
61. Love, M.I., Huber, W., Anders, S., Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol., 15, 2014, 550.
62. Luan, H., Lemon, W.C., Peabody, N.C., Pohl, J.B., Zelensky, P.K., Wang, D., Nitabach, M.N., Holmes, T.C., White, B.H., Functional dissection of a neuronal network required for cuticle tanning and wing expansion in Drosophila. J. Neurosci. 26 (2006), 573–584.
63. van der Maaten, L., Hinton, G., Visualizing data using t-SNE. J. Mach. Learn. Res. 9 (2008), 2579–2605.
64. Martinez-Jimenez, C.P., Eling, N., Chen, H.-C., Vallejos, C.A., Kolodziejczyk, A.A., Connor, F., Stojic, L., Rayner, T.F., Stubbington, M.J.T., Teichmann, S.A., et al. Aging increases cell-to-cell transcriptional variability upon immune stimulation. Science 355 (2017), 1433–1436.
65. Maurange, C., Cheng, L., Gould, A.P., Temporal transcription factors and their targets schedule the end of neural proliferation in Drosophila. Cell 133 (2008), 891–902.
66. McCarthy, D.J., Campbell, K.R., Lun, A.T.L., Wills, Q.F., Scater: pre-processing, quality control, normalization and visualization of single-cell RNA-seq data in R. Bioinformatics 33 (2017), 1179–1186.
67. McDavid, A., Finak, G., Chattopadyay, P.K., Dominguez, M., Lamoreaux, L., Ma, S.S., Roederer, M., Gottardo, R., Data exploration, quality control and testing in single-cell qPCR-based gene expression experiments. Bioinformatics 29 (2013), 461–467.
68. Medioni, C., Ramialison, M., Ephrussi, A., Besse, F., Imp promotes axonal remodeling by regulating profilin mRNA during brain development. Curr. Biol. 24 (2014), 793–800.
69. Melcher, C., Pankratz, M.J., Candidate gustatory interneurons modulating feeding behavior in the Drosophila brain. PLoS Biol., 3, 2005, e305.
70. Melnattur, K.V., Pursley, R., Lin, T.-Y., Ting, C.-Y., Smith, P.D., Pohida, T., Lee, C.-H., Multiple redundant medulla projection neurons mediate color vision in Drosophila. J. Neurogenet. 28 (2014), 374–388.
71. Min, S., Chae, H.-S., Jang, Y.-H., Choi, S., Lee, S., Jeong, Y.T., Jones, W.D., Moon, S.J., Kim, Y.-J., Chung, J., Identification of a peptidergic pathway critical to satiety responses in Drosophila. Curr. Biol. 26 (2016), 814–820.
72. Minocha, S., Boll, W., Noll, M., Crucial roles of Pox neuro in the developing ellipsoid body and antennal lobes of the Drosophila brain. PLoS ONE, 12, 2017, e0176002.
73. Miyamoto, T., Amrein, H., Diverse roles for the Drosophila fructose sensor Gr43a. Fly (Austin) 8 (2014), 19–25.
74. Montell, C., Rubin, G.M., The Drosophila ninaC locus encodes two photoreceptor cell specific proteins with domains homologous to protein kinases and the myosin heavy chain head. Cell 52 (1988), 757–772.
75. O'Sullivan, R.J., Karlseder, J., The great unravelling: chromatin as a modulator of the aging process. Trends Biochem. Sci. 37 (2012), 466–476.
76. Owald, D., Lin, S., Waddell, S., Light, heat, action: neural control of fruit fly behaviour. Philos. Trans. R. Soc. Lond. B Biol. Sci., 370, 2015, 20140211.
77. Pankova, K., Borst, A., RNA-seq transcriptome analysis of direction-selective T4/T5 neurons in Drosophila. PLoS ONE, 11, 2016, e0163986.
78. Park, D., Veenstra, J.A., Park, J.H., Taghert, P.H., Mapping peptidergic cells in Drosophila: where DIMM fits in. PLoS ONE, 3, 2008, e1896.
79. Park, J.H., Helfrich-Förster, C., Lee, G., Liu, L., Rosbash, M., Hall, J.C., Differential regulation of circadian pacemaker output by separate clock genes in Drosophila. Proc. Natl. Acad. Sci. USA 97 (2000), 3608–3613.
80. Parry, T.J., Theisen, J.W.M., Hsu, J.-Y., Wang, Y.-L., Corcoran, D.L., Eustice, M., Ohler, U., Kadonaga, J.T., The TCT motif, a key component of an RNA polymerase II transcription system for the translational machinery. Genes Dev. 24 (2010), 2013–2018.
81. Pedregosa, F., Varoquaux, G., Gramfort, A., Michel, V., Thirion, B., Grisel, O., Blondel, M., Prettenhofer, P., Weiss, R., Dubourg, V., et al. Scikit-learn: machine learning in Python. J. Mach. Learn. Res. 12 (2011), 2825–2830.
82. Porcelli, D., Barsanti, P., Pesole, G., Caggese, C., The nuclear OXPHOS genes in insecta: a common evolutionary origin, a common cis-regulatory motif, a common destiny for gene duplicates. BMC Evol. Biol., 7, 2007, 215.
83. Raj, B., Wagner, D.E., McKenna, A., Pandey, S., Klein, A.M., Shendure, J., Gagnon, J.A., Schier, A.F., Simultaneous single-cell profiling of lineages and cell types in the vertebrate brain. Nat. Biotechnol. 36 (2018), 442–450.
84. Regev, A., Teichmann, S.A., Lander, E.S., Amit, I., Benoist, C., Birney, E., Bodenmiller, B., Campbell, P., Carninci, P., Clatworthy, M., et al., Human Cell Atlas Meeting Participants. The human cell atlas. eLife, 6, 2017, e27041.
85. Robie, A.A., Hirokawa, J., Edwards, A.W., Umayam, L.A., Lee, A., Phillips, M.L., Card, G.M., Korff, W., Rubin, G.M., Simpson, J.H., et al. Mapping the neural substrates of behavior. Cell 170 (2017), 393–406.e28.
86. Robinson, M.D., McCarthy, D.J., Smyth, G.K., edgeR: a Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics 26 (2010), 139–140.
87. Rulifson, E.J., Kim, S.K., Nusse, R., Ablation of insulin-producing neurons in flies: growth and diabetic phenotypes. Science 296 (2002), 1118–1120.
88. Satija, R., Farrell, J.A., Gennert, D., Schier, A.F., Regev, A., Spatial reconstruction of single-cell gene expression data. Nat. Biotechnol. 33 (2015), 495–502.
89. Schinaman, J.M., Giesey, R.L., Mizutani, C.M., Lukacsovich, T., Sousa-Neves, R., The KRÜPPEL-like transcription factor DATILÓGRAFO is required in specific cholinergic neurons for sexual receptivity in Drosophila females. PLoS Biol., 12, 2014, e1001964.
90. Schindelin, J., Arganda-Carreras, I., Frise, E., Kaynig, V., Longair, M., Pietzsch, T., Preibisch, S., Rueden, C., Saalfeld, S., Schmid, B., et al. Fiji: an open-source platform for biological-image analysis. Nat. Methods 9 (2012), 676–682.
91. Soreq, L., Rose, J., Soreq, E., Hardy, J., Trabzuni, D., Cookson, M.R., Smith, C., Ryten, M., Patani, R., Ule, J. UK Brain Expression Consortium, North American Brain Expression Consortium. Major shifts in glial regional identity are a transcriptional hallmark of human brain aging. Cell Rep. 18 (2017), 557–570.
92. Spindler, S.R., Ortiz, I., Fung, S., Takashima, S., Hartenstein, V., Drosophila cortex and neuropile glia influence secondary axon tract growth, pathfinding, and fasciculation in the developing larval brain. Dev Biol 334 (2009), 355–368.
93. Srahna, M., Leyssen, M., Choi, C.M., Fradkin, L.G., Noordermeer, J.N., Hassan, B.A., A signaling network for patterning of neuronal connectivity in the Drosophila brain. PLoS Biol., 4, 2006, e348.
94. Stanescu, D.E., Yu, R., Won, K.-J., Stoffers, D.A., Single cell transcriptomic profiling of mouse pancreatic progenitors. Physiol. Genomics 49 (2017), 105–114.
95. Stork, T., Bernardos, R., Freeman, M.R., Analysis of glial cell development and function in Drosophila. Cold Spring Harb. Protoc. 2012 (2012), 1–17.
96. Syed, M.H., Mark, B., Doe, C.Q., Steroid hormone induction of temporal gene expression in Drosophila brain neuroblasts generates neuronal and glial diversity. eLife, 6, 2017, e26287.
97. Tahoe, N.M., Mokhtarzadeh, A., Curtsinger, J.W., Age-related RNA decline in adult Drosophila melanogaster. J Gerontol A Biol Sci Med Sci. 59 (2004), B896–B901.
98. Tan, L., Zhang, K.X., Pecot, M.Y., Nagarkar-Jaiswal, S., Lee, P.-T., Takemura, S.-Y., McEwen, J.M., Nern, A., Xu, S., Tadros, W., et al. Ig superfamily ligand and receptor pairs expressed in synaptic partners in Drosophila. Cell 163 (2015), 1756–1769.
99. Tulving, E., Craik, F.I.M., The Oxford Handbook of Memory. 2005, Oxford University Press, Oxford, New York.
100. Walter, W., Sánchez-Cabo, F., Ricote, M., GOplot: an R package for visually combining expression data with functional analysis. Bioinformatics 31 (2015), 2912–2914.
101. Wyss-Coray, T., Ageing, neurodegeneration and brain rejuvenation. Nature 539 (2016), 180–186.
102. Xiong, W.C., Okano, H., Patel, N.H., Blendy, J.A., Montell, C., repo encodes a glial-specific homeo domain protein required in the Drosophila nervous system. Genes Dev. 8 (1994), 981–994.
103. Yu, G., Wang, L.-G., Han, Y., He, Q.-Y., clusterProfiler: an R package for comparing biological themes among gene clusters. OMICS 16 (2012), 284–287.
104. Zeisel, A., Muñoz-Manchado, A.B., Codeluppi, S., Lönnerberg, P., La Manno, G., Juréus, A., Marques, S., Munguba, H., He, L., Betsholtz, C., et al. Brain structure. Cell types in the mouse cortex and hippocampus revealed by single-cell RNA-seq. Science 347 (2015), 1138–1142.
105. Zhu, S., Lin, S., Kao, C.-F., Awasaki, T., Chiang, A.-S., Lee, T., Gradients of the Drosophila Chinmo BTB-zinc finger protein govern neuronal temporal identity. Cell 127 (2006), 409–422.