Microglia: A Unique Versatile Cell in the Central Nervous System

ACS Chemical Neuroscience

Volumn 7, Issue 4, 2016, Pages 428-434

  Masuda, Takahiro ^a   Prinz, Marco ^a  

^a UNIVERSITY OF FREIBURG   (Germany)

Author keywords

brain; CNS; Microglia; multiple sclerosis; neuropathic pain; origin

Indexed keywords

CENTRAL NERVOUS SYSTEM; GLIA CELL; HUMAN; MICROGLIA; MULTIPLE SCLEROSIS; NERVE CELL; NEUROPATHIC PAIN; NONHUMAN; OBSESSIVE COMPULSIVE DISORDER; PRIORITY JOURNAL; REVIEW; VASCULARIZATION; ANIMAL; CYTOLOGY; PHYSIOLOGY;

ANIMALS; CENTRAL NERVOUS SYSTEM; HUMANS; MICROGLIA;

EID: 84966280571     PISSN: None     EISSN: 19487193     Source Type: Journal    
DOI: 10.1021/acschemneuro.5b00317     Document Type: Review

References (76)

1. Aguzzi, A., Barres, B. A., and Bennett, M. L. (2013) Microglia: scapegoat, saboteur, or something else? Science 339, 156-161 10.1126/science.1227901
2. Hoeffel, G., Chen, J., Lavin, Y., Low, D., Almeida, F. F., See, P., Beaudin, A. E., Lum, J., Low, I., Forsberg, E. C., Poidinger, M., Zolezzi, F., Larbi, A., Ng, L. G., Chan, J. K., Greter, M., Becher, B., Samokhvalov, I. M., Merad, M., and Ginhoux, F. (2015) C-Myb(+) erythro-myeloid progenitor-derived fetal monocytes give rise to adult tissue-resident macrophages Immunity 42, 665-678 10.1016/j.immuni.2015.03.011
3. Prinz, M. and Priller, J. (2014) Microglia and brain macrophages in the molecular age: from origin to neuropsychiatric disease Nat. Rev. Neurosci. 15, 300-312 10.1038/nrn3722
4. Ginhoux, F., Greter, M., Leboeuf, M., Nandi, S., See, P., Gokhan, S., Mehler, M. F., Conway, S. J., Ng, L. G., Stanley, E. R., Samokhvalov, I. M., and Merad, M. (2010) Fate mapping analysis reveals that adult microglia derive from primitive macrophages Science 330, 841-845 10.1126/science.1194637
5. Kierdorf, K., Erny, D., Goldmann, T., Sander, V., Schulz, C., Perdiguero, E. G., Wieghofer, P., Heinrich, A., Riemke, P., Holscher, C., Muller, D. N., Luckow, B., Brocker, T., Debowski, K., Fritz, G., Opdenakker, G., Diefenbach, A., Biber, K., Heikenwalder, M., Geissmann, F., Rosenbauer, F., and Prinz, M. (2013) Microglia emerge from erythromyeloid precursors via Pu.1- and Irf8-dependent pathways Nat. Neurosci. 16, 273-280 10.1038/nn.3318
6. Zusso, M., Methot, L., Lo, R., Greenhalgh, A. D., David, S., and Stifani, S. (2012) Regulation of postnatal forebrain amoeboid microglial cell proliferation and development by the transcription factor Runx1 J. Neurosci. 32, 11285-11298 10.1523/JNEUROSCI.6182-11.2012
7. Schulz, C., Gomez Perdiguero, E., Chorro, L., Szabo-Rogers, H., Cagnard, N., Kierdorf, K., Prinz, M., Wu, B., Jacobsen, S. E., Pollard, J. W., Frampton, J., Liu, K. J., and Geissmann, F. (2012) A lineage of myeloid cells independent of Myb and hematopoietic stem cells Science 336, 86-90 10.1126/science.1219179
8. Yona, S., Kim, K. W., Wolf, Y., Mildner, A., Varol, D., Breker, M., Strauss-Ayali, D., Viukov, S., Guilliams, M., Misharin, A., Hume, D. A., Perlman, H., Malissen, B., Zelzer, E., and Jung, S. (2013) Fate mapping reveals origins and dynamics of monocytes and tissue macrophages under homeostasis Immunity 38, 79-91 10.1016/j.immuni.2012.12.001
9. Hashimoto, D., Chow, A., Noizat, C., Teo, P., Beasley, M. B., Leboeuf, M., Becker, C. D., See, P., Price, J., Lucas, D., Greter, M., Mortha, A., Boyer, S. W., Forsberg, E. C., Tanaka, M., van Rooijen, N., Garcia-Sastre, A., Stanley, E. R., Ginhoux, F., Frenette, P. S., and Merad, M. (2013) Tissue-resident macrophages self-maintain locally throughout adult life with minimal contribution from circulating monocytes Immunity 38, 792-804 10.1016/j.immuni.2013.04.004
10. Erblich, B., Zhu, L., Etgen, A. M., Dobrenis, K., and Pollard, J. W. (2011) Absence of colony stimulation factor-1 receptor results in loss of microglia, disrupted brain development and olfactory deficits PLoS One 6, e26317 10.1371/journal.pone.0026317
11. Wang, Y., Szretter, K. J., Vermi, W., Gilfillan, S., Rossini, C., Cella, M., Barrow, A. D., Diamond, M. S., and Colonna, M. (2012) IL-34 is a tissue-restricted ligand of CSF1R required for the development of Langerhans cells and microglia Nat. Immunol. 13, 753-760 10.1038/ni.2360
12. Greter, M., Lelios, I., Pelczar, P., Hoeffel, G., Price, J., Leboeuf, M., Kundig, T. M., Frei, K., Ginhoux, F., Merad, M., and Becher, B. (2012) Stroma-derived interleukin-34 controls the development and maintenance of langerhans cells and the maintenance of microglia Immunity 37, 1050-1060 10.1016/j.immuni.2012.11.001
13. Butovsky, O., Jedrychowski, M. P., Moore, C. S., Cialic, R., Lanser, A. J., Gabriely, G., Koeglsperger, T., Dake, B., Wu, P. M., Doykan, C. E., Fanek, Z., Liu, L., Chen, Z., Rothstein, J. D., Ransohoff, R. M., Gygi, S. P., Antel, J. P., and Weiner, H. L. (2014) Identification of a unique TGF-beta-dependent molecular and functional signature in microglia Nat. Neurosci. 17, 131-143 10.1038/nn.3599
14. Gosselin, D., Link, V. M., Romanoski, C. E., Fonseca, G. J., Eichenfield, D. Z., Spann, N. J., Stender, J. D., Chun, H. B., Garner, H., Geissmann, F., and Glass, C. K. (2014) Environment drives selection and function of enhancers controlling tissue-specific macrophage identities Cell 159, 1327-1340 10.1016/j.cell.2014.11.023
15. Xu, J., Zhu, L., He, S., Wu, Y., Jin, W., Yu, T., Qu, J. Y., and Wen, Z. (2015) Temporal-Spatial Resolution Fate Mapping Reveals Distinct Origins for Embryonic and Adult Microglia in Zebrafish Dev. Cell 34, 632-641 10.1016/j.devcel.2015.08.018
16. Ajami, B., Bennett, J. L., Krieger, C., McNagny, K. M., and Rossi, F. M. (2011) Infiltrating monocytes trigger EAE progression, but do not contribute to the resident microglia pool Nat. Neurosci. 14, 1142-1149 10.1038/nn.2887
17. Mildner, A., Schmidt, H., Nitsche, M., Merkler, D., Hanisch, U. K., Mack, M., Heikenwalder, M., Bruck, W., Priller, J., and Prinz, M. (2007) Microglia in the adult brain arise from Ly-6ChiCCR2+ monocytes only under defined host conditions Nat. Neurosci. 10, 1544-1553 10.1038/nn2015
18. Gomez Perdiguero, E., Klapproth, K., Schulz, C., Busch, K., Azzoni, E., Crozet, L., Garner, H., Trouillet, C., de Bruijn, M. F., Geissmann, F., and Rodewald, H. R. (2015) Tissue-resident macrophages originate from yolk-sac-derived erythro-myeloid progenitors Nature 518, 547-551 10.1038/nature13989
19. Ajami, B., Bennett, J. L., Krieger, C., Tetzlaff, W., and Rossi, F. M. (2007) Local self-renewal can sustain CNS microglia maintenance and function throughout adult life Nat. Neurosci. 10, 1538-1543 10.1038/nn2014
20. Bruttger, J., Karram, K., Wortge, S., Regen, T., Marini, F., Hoppmann, N., Klein, M., Blank, T., Yona, S., Wolf, Y., Mack, M., Pinteaux, E., Muller, W., Zipp, F., Binder, H., Bopp, T., Prinz, M., Jung, S., and Waisman, A. (2015) Genetic Cell Ablation Reveals Clusters of Local Self-Renewing Microglia in the Mammalian Central Nervous System Immunity 43, 92-106 10.1016/j.immuni.2015.06.012
21. Elmore, M. R., Najafi, A. R., Koike, M. A., Dagher, N. N., Spangenberg, E. E., Rice, R. A., Kitazawa, M., Matusow, B., Nguyen, H., West, B. L., and Green, K. N. (2014) Colony-stimulating factor 1 receptor signaling is necessary for microglia viability, unmasking a microglia progenitor cell in the adult brain Neuron 82, 380-397 10.1016/j.neuron.2014.02.040
22. Erny, D., Hrabe de Angelis, A. L., Jaitin, D., Wieghofer, P., Staszewski, O., David, E., Keren-Shaul, H., Mahlakoiv, T., Jakobshagen, K., Buch, T., Schwierzeck, V., Utermohlen, O., Chun, E., Garrett, W. S., McCoy, K. D., Diefenbach, A., Staeheli, P., Stecher, B., Amit, I., and Prinz, M. (2015) Host microbiota constantly control maturation and function of microglia in the CNS Nat. Neurosci. 18, 965-977 10.1038/nn.4030
23. Borre, Y. E., Moloney, R. D., Clarke, G., Dinan, T. G., and Cryan, J. F. (2014) The impact of microbiota on brain and behavior: mechanisms & therapeutic potential Adv. Exp. Med. Biol. 817, 373-403 10.1007/978-1-4939-0897-4-17
24. Sudo, N., Chida, Y., Aiba, Y., Sonoda, J., Oyama, N., Yu, X. N., Kubo, C., and Koga, Y. (2004) Postnatal microbial colonization programs the hypothalamic-pituitary-adrenal system for stress response in mice J. Physiol. 558, 263-275 10.1113/jphysiol.2004.063388
25. Schmidt, C. (2015) Mental health: thinking from the gut Nature 518, S12-15 10.1038/518S13a
26. Kettenmann, H., Kirchhoff, F., and Verkhratsky, A. (2013) Microglia: new roles for the synaptic stripper Neuron 77, 10-18 10.1016/j.neuron.2012.12.023
27. Salter, M. W. and Beggs, S. (2014) Sublime microglia: expanding roles for the guardians of the CNS Cell 158, 15-24 10.1016/j.cell.2014.06.008
28. Nimmerjahn, A., Kirchhoff, F., and Helmchen, F. (2005) Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo Science 308, 1314-1318 10.1126/science.1110647
29. Haynes, S. E., Hollopeter, G., Yang, G., Kurpius, D., Dailey, M. E., Gan, W. B., and Julius, D. (2006) The P2Y12 receptor regulates microglial activation by extracellular nucleotides Nat. Neurosci. 9, 1512-1519 10.1038/nn1805
30. Wu, L. J., Vadakkan, K. I., and Zhuo, M. (2007) ATP-induced chemotaxis of microglial processes requires P2Y receptor-activated initiation of outward potassium currents Glia 55, 810-821 10.1002/glia.20500
31. Koizumi, S., Shigemoto-Mogami, Y., Nasu-Tada, K., Shinozaki, Y., Ohsawa, K., Tsuda, M., Joshi, B. V., Jacobson, K. A., Kohsaka, S., and Inoue, K. (2007) UDP acting at P2Y6 receptors is a mediator of microglial phagocytosis Nature 446, 1091-1095 10.1038/nature05704
32. Sierra, A., Abiega, O., Shahraz, A., and Neumann, H. (2013) Janus-faced microglia: beneficial and detrimental consequences of microglial phagocytosis Front. Cell. Neurosci. 7, 6 10.3389/fncel.2013.00006
33. Wake, H., Moorhouse, A. J., Jinno, S., Kohsaka, S., and Nabekura, J. (2009) Resting microglia directly monitor the functional state of synapses in vivo and determine the fate of ischemic terminals J. Neurosci. 29, 3974-3980 10.1523/JNEUROSCI.4363-08.2009
34. Tremblay, M. E., Lowery, R. L., and Majewska, A. K. (2010) Microglial interactions with synapses are modulated by visual experience PLoS Biol. 8, e1000527 10.1371/journal.pbio.1000527
35. Paolicelli, R. C., Bolasco, G., Pagani, F., Maggi, L., Scianni, M., Panzanelli, P., Giustetto, M., Ferreira, T. A., Guiducci, E., Dumas, L., Ragozzino, D., and Gross, C. T. (2011) Synaptic pruning by microglia is necessary for normal brain development Science 333, 1456-1458 10.1126/science.1202529
36. Schafer, D. P., Lehrman, E. K., Kautzman, A. G., Koyama, R., Mardinly, A. R., Yamasaki, R., Ransohoff, R. M., Greenberg, M. E., Barres, B. A., and Stevens, B. (2012) Microglia sculpt postnatal neural circuits in an activity and complement-dependent manner Neuron 74, 691-705 10.1016/j.neuron.2012.03.026
37. Gemma, C. and Bachstetter, A. D. (2013) The role of microglia in adult hippocampal neurogenesis Front. Cell. Neurosci. 7, 229 10.3389/fncel.2013.00229
38. Sierra, A., Encinas, J. M., Deudero, J. J., Chancey, J. H., Enikolopov, G., Overstreet-Wadiche, L. S., Tsirka, S. E., and Maletic-Savatic, M. (2010) Microglia shape adult hippocampal neurogenesis through apoptosis-coupled phagocytosis Cell Stem Cell 7, 483-495 10.1016/j.stem.2010.08.014
39. Brown, G. C. and Neher, J. J. (2014) Microglial phagocytosis of live neurons Nat. Rev. Neurosci. 15, 209-216 10.1038/nrn3710
40. Duffield, J. S., Forbes, S. J., Constandinou, C. M., Clay, S., Partolina, M., Vuthoori, S., Wu, S., Lang, R., and Iredale, J. P. (2005) Selective depletion of macrophages reveals distinct, opposing roles during liver injury and repair J. Clin. Invest. 115, 56-65 10.1172/JCI200522675
41. Parkhurst, C. N., Yang, G., Ninan, I., Savas, J. N., Yates, J. R., 3rd, Lafaille, J. J., Hempstead, B. L., Littman, D. R., and Gan, W. B. (2013) Microglia promote learning-dependent synapse formation through brain-derived neurotrophic factor Cell 155, 1596-1609 10.1016/j.cell.2013.11.030
42. Chao, M. V. (2003) Neurotrophins and their receptors: a convergence point for many signalling pathways Nat. Rev. Neurosci. 4, 299-309 10.1038/nrn1078
43. Ueno, M., Fujita, Y., Tanaka, T., Nakamura, Y., Kikuta, J., Ishii, M., and Yamashita, T. (2013) Layer V cortical neurons require microglial support for survival during postnatal development Nat. Neurosci. 16, 543-551 10.1038/nn.3358
44. Goldmann, T. and Prinz, M. (2013) Role of microglia in CNS autoimmunity Clin. Dev. Immunol. 2013, 208093 10.1155/2013/208093
45. Batoulis, H., Recks, M. S., Addicks, K., and Kuerten, S. (2011) Experimental autoimmune encephalomyelitis - achievements and prospective advances Apmis 119, 819-830 10.1111/j.1600-0463.2011.02794.x
46. Croxford, A. L., Kurschus, F. C., and Waisman, A. (2011) Mouse models for multiple sclerosis: historical facts and future implications Biochim. Biophys. Acta, Mol. Basis Dis. 1812, 177-183 10.1016/j.bbadis.2010.06.010
47. Xiao, Y., Jin, J., Chang, M., Chang, J. H., Hu, H., Zhou, X., Brittain, G. C., Stansberg, C., Torkildsen, O., Wang, X., Brink, R., Cheng, X., and Sun, S. C. (2013) Peli1 promotes microglia-mediated CNS inflammation by regulating Traf3 degradation Nat. Med. 19, 595-602 10.1038/nm.3111
48. Yamasaki, R., Lu, H., Butovsky, O., Ohno, N., Rietsch, A. M., Cialic, R., Wu, P. M., Doykan, C. E., Lin, J., Cotleur, A. C., Kidd, G., Zorlu, M. M., Sun, N., Hu, W., Liu, L., Lee, J. C., Taylor, S. E., Uehlein, L., Dixon, D., Gu, J., Floruta, C. M., Zhu, M., Charo, I. F., Weiner, H. L., and Ransohoff, R. M. (2014) Differential roles of microglia and monocytes in the inflamed central nervous system J. Exp. Med. 211, 1533-1549 10.1084/jem.20132477
49. Wieghofer, P. and Prinz, M. (2015) Genetic manipulation of microglia during brain development and disease Biochim. Biophys. Acta, Mol. Basis Dis. 10.1016/j.bbadis.2015.09.019
50. Goldmann, T., Wieghofer, P., Muller, P. F., Wolf, Y., Varol, D., Yona, S., Brendecke, S. M., Kierdorf, K., Staszewski, O., Datta, M., Luedde, T., Heikenwalder, M., Jung, S., and Prinz, M. (2013) A new type of microglia gene targeting shows TAK1 to be pivotal in CNS autoimmune inflammation Nat. Neurosci. 16, 1618-1626 10.1038/nn.3531
51. Hiremath, M. M., Saito, Y., Knapp, G. W., Ting, J. P., Suzuki, K., and Matsushima, G. K. (1998) Microglial/macrophage accumulation during cuprizone-induced demyelination in C57BL/6 mice J. Neuroimmunol. 92, 38-49 10.1016/S0165-5728(98)00168-4
52. Arnett, H. A., Mason, J., Marino, M., Suzuki, K., Matsushima, G. K., and Ting, J. P. (2001) TNF alpha promotes proliferation of oligodendrocyte progenitors and remyelination Nat. Neurosci. 4, 1116-1122 10.1038/nn738
53. Wu, L. J., Wu, G., Akhavan Sharif, M. R., Baker, A., Jia, Y., Fahey, F. H., Luo, H. R., Feener, E. P., and Clapham, D. E. (2012) The voltage-gated proton channel Hv1 enhances brain damage from ischemic stroke Nat. Neurosci. 15, 565-573 10.1038/nn.3059
54. Liu, J., Tian, D., Murugan, M., Eyo, U. B., Dreyfus, C. F., Wang, W., and Wu, L. J. (2015) Microglial Hv1 proton channel promotes cuprizone-induced demyelination through oxidative damage J. Neurochem. 135, 347-356 10.1111/jnc.13242
55. Tsuda, M., Masuda, T., Tozaki-Saitoh, H., and Inoue, K. (2013) Microglial regulation of neuropathic pain J. Pharmacol. Sci. 121, 89-94 10.1254/jphs.12R14CP
56. Calvo, M. and Bennett, D. L. (2012) The mechanisms of microgliosis and pain following peripheral nerve injury Exp. Neurol. 234, 271-282 10.1016/j.expneurol.2011.08.018
57. Echeverry, S., Shi, X. Q., and Zhang, J. (2008) Characterization of cell proliferation in rat spinal cord following peripheral nerve injury and the relationship with neuropathic pain Pain 135, 37-47 10.1016/j.pain.2007.05.002
58. Tsuda, M., Shigemoto-Mogami, Y., Koizumi, S., Mizokoshi, A., Kohsaka, S., Salter, M. W., and Inoue, K. (2003) P2×4 receptors induced in spinal microglia gate tactile allodynia after nerve injury Nature 424, 778-783 10.1038/nature01786
59. Tsuda, M., Masuda, T., Kitano, J., Shimoyama, H., Tozaki-Saitoh, H., and Inoue, K. (2009) IFN-gamma receptor signaling mediates spinal microglia activation driving neuropathic pain Proc. Natl. Acad. Sci. U. S. A. 106, 8032-8037 10.1073/pnas.0810420106
60. Zhang, J., Shi, X. Q., Echeverry, S., Mogil, J. S., De Koninck, Y., and Rivest, S. (2007) Expression of CCR2 in both resident and bone marrow-derived microglia plays a critical role in neuropathic pain J. Neurosci. 27, 12396-12406 10.1523/JNEUROSCI.3016-07.2007
61. Beggs, S., Trang, T., and Salter, M. W. (2012) P2×4R+ microglia drive neuropathic pain Nat. Neurosci. 15, 1068-1073 10.1038/nn.3155
62. Ulmann, L., Hatcher, J. P., Hughes, J. P., Chaumont, S., Green, P. J., Conquet, F., Buell, G. N., Reeve, A. J., Chessell, I. P., and Rassendren, F. (2008) Up-regulation of P2×4 receptors in spinal microglia after peripheral nerve injury mediates BDNF release and neuropathic pain J. Neurosci. 28, 11263-11268 10.1523/JNEUROSCI.2308-08.2008
63. Tsuda, M., Kuboyama, K., Inoue, T., Nagata, K., Tozaki-Saitoh, H., and Inoue, K. (2009) Behavioral phenotypes of mice lacking purinergic P2×4 receptors in acute and chronic pain assays Mol. Pain 5, 28 10.1186/1744-8069-5-28
64. Beggs, S. and Salter, M. W. (2013) The known knowns of microglia-neuronal signalling in neuropathic pain Neurosci. Lett. 557, 37-42 10.1016/j.neulet.2013.08.037
65. Masuda, T., Tsuda, M., Yoshinaga, R., Tozaki-Saitoh, H., Ozato, K., Tamura, T., and Inoue, K. (2012) IRF8 is a critical transcription factor for transforming microglia into a reactive phenotype Cell Rep. 1, 334-340 10.1016/j.celrep.2012.02.014
66. Nasu-Tada, K., Koizumi, S., Tsuda, M., Kunifusa, E., and Inoue, K. (2006) Possible involvement of increase in spinal fibronectin following peripheral nerve injury in upregulation of microglial P2×4, a key molecule for mechanical allodynia Glia 53, 769-775 10.1002/glia.20339
67. Masuda, T., Iwamoto, S., Yoshinaga, R., Tozaki-Saitoh, H., Nishiyama, A., Mak, T. W., Tamura, T., Tsuda, M., and Inoue, K. (2014) Transcription factor IRF5 drives P2×4R+-reactive microglia gating neuropathic pain Nat. Commun. 5, 3771 10.1038/ncomms4771
68. Coull, J. A., Beggs, S., Boudreau, D., Boivin, D., Tsuda, M., Inoue, K., Gravel, C., Salter, M. W., and De Koninck, Y. (2005) BDNF from microglia causes the shift in neuronal anion gradient underlying neuropathic pain Nature 438, 1017-1021 10.1038/nature04223
69. Sorge, R. E., Mapplebeck, J. C., Rosen, S., Beggs, S., Taves, S., Alexander, J. K., Martin, L. J., Austin, J. S., Sotocinal, S. G., Chen, D., Yang, M., Shi, X. Q., Huang, H., Pillon, N. J., Bilan, P. J., Tu, Y., Klip, A., Ji, R. R., Zhang, J., Salter, M. W., and Mogil, J. S. (2015) Different immune cells mediate mechanical pain hypersensitivity in male and female mice Nat. Neurosci. 18, 1081-1083 10.1038/nn.4053
70. Guo, L. H. and Schluesener, H. J. (2005) Lesional accumulation of P2X(4) receptor(+) macrophages in rat CNS during experimental autoimmune encephalomyelitis Neuroscience 134, 199-205 10.1016/j.neuroscience.2005.04.026
71. Vazquez-Villoldo, N., Domercq, M., Martin, A., Llop, J., Gomez-Vallejo, V., and Matute, C. (2014) P2×4 receptors control the fate and survival of activated microglia Glia 62, 171-184 10.1002/glia.22596
72. Zeisel, A., Munoz-Manchado, A. B., Codeluppi, S., Lonnerberg, P., La Manno, G., Jureus, A., Marques, S., Munguba, H., He, L., Betsholtz, C., Rolny, C., Castelo-Branco, G., Hjerling-Leffler, J., and Linnarsson, S. (2015) Brain structure. Cell types in the mouse cortex and hippocampus revealed by single-cell RNA-seq Science 347, 1138-1142 10.1126/science.aaa1934
73. Hickman, S. E., Kingery, N. D., Ohsumi, T. K., Borowsky, M. L., Wang, L. C., Means, T. K., and El Khoury, J. (2013) The microglial sensome revealed by direct RNA sequencing Nat. Neurosci. 16, 1896-1905 10.1038/nn.3554
74. Gautier, E. L., Shay, T., Miller, J., Greter, M., Jakubzick, C., Ivanov, S., Helft, J., Chow, A., Elpek, K. G., Gordonov, S., Mazloom, A. R., Ma'ayan, A., Chua, W. J., Hansen, T. H., Turley, S. J., Merad, M., Randolph, G. J., and the Immunological Genome Consortium (2012) Gene-expression profiles and transcriptional regulatory pathways that underlie the identity and diversity of mouse tissue macrophages Nat. Immunol. 13, 1118-1128 10.1038/ni.2419
75. Chen, S. K., Tvrdik, P., Peden, E., Cho, S., Wu, S., Spangrude, G., and Capecchi, M. R. (2010) Hematopoietic origin of pathological grooming in Hoxb8 mutant mice Cell 141, 775-785 10.1016/j.cell.2010.03.055
76. Horwath, E. and Weissman, M. M. (2000) The epidemiology and cross-national presentation of obsessive-compulsive disorder Psychiatr Clin North Am. 23, 493-507 10.1016/S0193-953X(05)70176-3