publication . Article . Preprint . Other literature type . 2018

Loss of Trem2 in microglia leads to widespread disruption of cell co-expression networks in mouse brain

Carbajosa, Guillermo; Malki, Karim; Lawless, Nathan; Wang, Hong; Ryder, John W.; Wozniak, Eva; Wood, Kristie; Mein, Charles A.; Dobson, Richard J.B.; Collier, David A.; ...
  • Published: 01 Sep 2018
  • Country: United Kingdom
Abstract
<jats:title>Abstract</jats:title><jats:p>Rare heterozygous coding variants in the Triggering Receptor Expressed in Myeloid cells 2 (TREM2) gene, conferring increased risk of developing late-onset Alzheimer's disease, have been identified. We examined the transcriptional consequences of the loss of Trem2 in mouse brain to better understand its role in disease using differential expression and coexpression network analysis of Trem2 knockout and wild-type mice. We generated RNA-Seq data from cortex and hippocampus sampled at 4 and 8 months. Using brain cell type markers and ontology enrichment, we found subnetworks with cell type and/or functional identity. We prim...
Subjects
free text keywords: Alzheimer's disease, Endothelial cells, Knockout mouse model, RNA-Seq, Weighted gene coexpression network analysis, /dk/atira/pure/subjectarea/asjc/2800, Neuroscience(all), /dk/atira/pure/subjectarea/asjc/1300/1302, /dk/atira/pure/subjectarea/asjc/2700/2728, /dk/atira/pure/subjectarea/asjc/1300/1309, /dk/atira/pure/subjectarea/asjc/2700/2717, Developmental Biology, Ageing, General Neuroscience, Geriatrics and Gerontology, Clinical Neurology, Microglia, medicine.anatomical_structure, medicine, Psychology, Cell type, Receptor, Cell biology, Cell, TREM2, Gene, Endocrinology, medicine.medical_specialty, Amyloid precursor protein, biology.protein, biology, Internal medicine, Hippocampus, Genetics, Article, Science & Technology, Life Sciences & Biomedicine, Geriatrics & Gerontology, Neurosciences, Neurosciences & Neurology, TREM2, Alzheimer's disease, Weighted gene coexpression network analysis, RNA-Seq, Knockout mouse model, Endothelial cells, AMYOTROPHIC-LATERAL-SCLEROSIS, ONSET ALZHEIMERS-DISEASE, NASU-HAKOLA-DISEASE, MYELOID CELLS, GENE-EXPRESSION, FRONTOTEMPORAL DEMENTIA, PRESENILE-DEMENTIA, SQSTM1 MUTATIONS, COMMON VARIANTS, CANCER INVASION
Funded by
EC| PHAGO
Project
PHAGO
Inflammation and AD: modulating microglia function focussing on TREM2 and CD33 - Sofia ref.: 115976
  • Funder: European Commission (EC)
  • Project Code: 115976
  • Funding stream: H2020 | IMI2-RIA
106 references, page 1 of 8

Atagi, Y., Liu, C.C., Painter, M.M., Chen, X.-F., Verbeeck, C., Zheng, H., Li, X., Rademakers, R., Kang, S.S., Xu, H., Younkin, S., Das, P., Fryer, J.D., Bu, G.. Apolipoprotein E is a ligand for triggering receptor expressed on myeloid cells 2 (TREM2). J. Biol. Chem.. 2015; 290: 26043-26050 [OpenAIRE] [PubMed]

Benitez, B.A., Jin, S.C., Guerreiro, R., Graham, R., Lord, J., Harold, D., Sims, R., Lambert, J.C., Gibbs, J.R., Bras, J., Sassi, C., Harari, O., Bertelsen, S., Lupton, M.K., Powell, J., Bellenguez, C., Brown, K., Medway, C., Haddick, P.C.G., Van der Brug, M.P., Bhangale, T., Ortmann, W., Behrens, T., Mayeux, R., Pericak-Vance, M.A., Farrer, L.A., Schellenberg, G.D., Haines, J.L., Turton, J., Braae, A., Barber, I., Fagan, A.M., Holtzman, D.M., Morris, J.C., Williams, J., Kauwe, J.S.K., Amouyel, P., Morgan, K., Singleton, A., Hardy, J., Goate, A.M., Cruchaga, C.. Missense variant in TREML2 protects against Alzheimer’s disease. Neurobiol. Aging. 2014; 35: 1510.e19-1510.e26

Borroni, B., Ferrari, F., Galimberti, D., Nacmias, B., Barone, C., Bagnoli, S., Fenoglio, C., Piaceri, I., Archetti, S., Bonvicini, C., Gennarelli, M., Turla, M., Scarpini, E., Sorbi, S., Padovani, A.. Heterozygous TREM2 mutations in frontotemporal dementia. Neurobiol. Aging. 2014; 35

Braak, H., Braak, E.. Frequency of stages of Alzheimer-related lesions in different age categories. Neurobiol. Aging. 1997; 18: 351-357 [PubMed]

Bray, N.L., Pimentel, H., Melsted, P., Pachter, L.. Near-optimal probabilistic RNA-seq quantification. Nat. Biotechnol.. 2016; 34: 525-527 [OpenAIRE] [PubMed]

Brendel, M., Kleinberger, G., Probst, F., Jaworska, A., Overhoff, F., Blume, T., Albert, N.L., Carlsen, J., Lindner, S., Gildehaus, F.J., Ozmen, L., Suárez-Calvet, M., Bartenstein, P., Baumann, K., Ewers, M., Herms, J., Haass, C., Rominger, A.. Increase of TREM2 during aging of an Alzheimer’s disease mouse model is paralleled by microglial activation and amyloidosis. Front. Aging Neurosci.. 2017; 9: 8 [OpenAIRE] [PubMed]

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., Weiner, H.L.. Identification of a unique TGF-β-dependent molecular and functional signature in microglia. Nat. Neurosci.. 2014; 17: 131-143 [OpenAIRE] [PubMed]

Cannon, J.P., O’Driscoll, M., Litman, G.W.. Specific lipid recognition is a general feature of CD300 and TREM molecules. Immunogenetics. 2012; 64: 39-47 [PubMed]

Cantoni, C., Bollman, B., Licastro, D., Xie, M., Mikesell, R., Schmidt, R., Yuede, C.M., Galimberti, D., Olivecrona, G., Klein, R.S., Cross, A.H., Otero, K., Piccio, L.. TREM2 regulates microglial cell activation in response to demyelination in vivo. Acta Neuropathol.. 2015; 129: 429-447 [OpenAIRE] [PubMed]

Carrasquillo, M.M., Allen, M., Burgess, J.D., Wang, X., Strickland, S.L., Aryal, S., Siuda, J., Kachadoorian, M.L., Medway, C., Younkin, C.S., Nair, A., Wang, C., Chanana, P., Serie, D., Nguyen, T., Lincoln, S., Malphrus, K.G., Morgan, K., Golde, T.E., Price, N.D., White, C.C., De Jager, P.L., Bennett, D.A., Asmann, Y.W., Crook, J.E., Petersen, R.C., Graff-Radford, N.R., Dickson, D.W., Younkin, S.G., Ertekin-Taner, N.. A candidate regulatory variant at the TREM gene cluster associates with decreased Alzheimer’s disease risk and increased TREML1 and TREM2 brain gene expression. Alzheimers Dement. 2016; 13: 663-673 [OpenAIRE] [PubMed]

Castranio, E.L., Mounier, A., Wolfe, C.M., Nam, K.N., Fitz, N.F., Letronne, F., Schug, J., Koldamova, R., Lefterov, I.. Gene co-expression networks identify Trem2 and Tyrobp as major hubs in human APOE expressing mice following traumatic brain injury. Neurobiol. Dis.. 2017; 105: 1-14 [OpenAIRE] [PubMed]

Chen, E.Y., Tan, C.M., Kou, Y., Duan, Q., Wang, Z., Meirelles, G.V., Clark, N.R., Ma’ayan, A.. Enrichr: interactive and collaborative HTML5 gene list enrichment analysis tool. BMC Bioinformatics. 2013; 14: 128 [OpenAIRE] [PubMed]

Chertoff, M., Shrivastava, K., Gonzalez, B., Acarin, L., Giménez-Llort, L.. Differential modulation of TREM2 protein during postnatal brain development in mice. PLoS One. 2013; 8: e72083 [OpenAIRE] [PubMed]

Conde, J.R., Streit, W.J.. Microglia in the aging brain. J. Neuropathol. Exp. Neurol.. 2006; 65: 199-203 [PubMed]

Daws, M.R., Sullam, P.M., Niemi, E.C., Chen, T.T., Tchao, N.K., Seaman, W.E.. Pattern recognition by TREM-2: binding of anionic ligands. J. Immunol.. 2003; 171: 594-599 [OpenAIRE] [PubMed]

106 references, page 1 of 8
Abstract
<jats:title>Abstract</jats:title><jats:p>Rare heterozygous coding variants in the Triggering Receptor Expressed in Myeloid cells 2 (TREM2) gene, conferring increased risk of developing late-onset Alzheimer's disease, have been identified. We examined the transcriptional consequences of the loss of Trem2 in mouse brain to better understand its role in disease using differential expression and coexpression network analysis of Trem2 knockout and wild-type mice. We generated RNA-Seq data from cortex and hippocampus sampled at 4 and 8 months. Using brain cell type markers and ontology enrichment, we found subnetworks with cell type and/or functional identity. We prim...
Subjects
free text keywords: Alzheimer's disease, Endothelial cells, Knockout mouse model, RNA-Seq, Weighted gene coexpression network analysis, /dk/atira/pure/subjectarea/asjc/2800, Neuroscience(all), /dk/atira/pure/subjectarea/asjc/1300/1302, /dk/atira/pure/subjectarea/asjc/2700/2728, /dk/atira/pure/subjectarea/asjc/1300/1309, /dk/atira/pure/subjectarea/asjc/2700/2717, Developmental Biology, Ageing, General Neuroscience, Geriatrics and Gerontology, Clinical Neurology, Microglia, medicine.anatomical_structure, medicine, Psychology, Cell type, Receptor, Cell biology, Cell, TREM2, Gene, Endocrinology, medicine.medical_specialty, Amyloid precursor protein, biology.protein, biology, Internal medicine, Hippocampus, Genetics, Article, Science & Technology, Life Sciences & Biomedicine, Geriatrics & Gerontology, Neurosciences, Neurosciences & Neurology, TREM2, Alzheimer's disease, Weighted gene coexpression network analysis, RNA-Seq, Knockout mouse model, Endothelial cells, AMYOTROPHIC-LATERAL-SCLEROSIS, ONSET ALZHEIMERS-DISEASE, NASU-HAKOLA-DISEASE, MYELOID CELLS, GENE-EXPRESSION, FRONTOTEMPORAL DEMENTIA, PRESENILE-DEMENTIA, SQSTM1 MUTATIONS, COMMON VARIANTS, CANCER INVASION
Funded by
EC| PHAGO
Project
PHAGO
Inflammation and AD: modulating microglia function focussing on TREM2 and CD33 - Sofia ref.: 115976
  • Funder: European Commission (EC)
  • Project Code: 115976
  • Funding stream: H2020 | IMI2-RIA
106 references, page 1 of 8

Atagi, Y., Liu, C.C., Painter, M.M., Chen, X.-F., Verbeeck, C., Zheng, H., Li, X., Rademakers, R., Kang, S.S., Xu, H., Younkin, S., Das, P., Fryer, J.D., Bu, G.. Apolipoprotein E is a ligand for triggering receptor expressed on myeloid cells 2 (TREM2). J. Biol. Chem.. 2015; 290: 26043-26050 [OpenAIRE] [PubMed]

Benitez, B.A., Jin, S.C., Guerreiro, R., Graham, R., Lord, J., Harold, D., Sims, R., Lambert, J.C., Gibbs, J.R., Bras, J., Sassi, C., Harari, O., Bertelsen, S., Lupton, M.K., Powell, J., Bellenguez, C., Brown, K., Medway, C., Haddick, P.C.G., Van der Brug, M.P., Bhangale, T., Ortmann, W., Behrens, T., Mayeux, R., Pericak-Vance, M.A., Farrer, L.A., Schellenberg, G.D., Haines, J.L., Turton, J., Braae, A., Barber, I., Fagan, A.M., Holtzman, D.M., Morris, J.C., Williams, J., Kauwe, J.S.K., Amouyel, P., Morgan, K., Singleton, A., Hardy, J., Goate, A.M., Cruchaga, C.. Missense variant in TREML2 protects against Alzheimer’s disease. Neurobiol. Aging. 2014; 35: 1510.e19-1510.e26

Borroni, B., Ferrari, F., Galimberti, D., Nacmias, B., Barone, C., Bagnoli, S., Fenoglio, C., Piaceri, I., Archetti, S., Bonvicini, C., Gennarelli, M., Turla, M., Scarpini, E., Sorbi, S., Padovani, A.. Heterozygous TREM2 mutations in frontotemporal dementia. Neurobiol. Aging. 2014; 35

Braak, H., Braak, E.. Frequency of stages of Alzheimer-related lesions in different age categories. Neurobiol. Aging. 1997; 18: 351-357 [PubMed]

Bray, N.L., Pimentel, H., Melsted, P., Pachter, L.. Near-optimal probabilistic RNA-seq quantification. Nat. Biotechnol.. 2016; 34: 525-527 [OpenAIRE] [PubMed]

Brendel, M., Kleinberger, G., Probst, F., Jaworska, A., Overhoff, F., Blume, T., Albert, N.L., Carlsen, J., Lindner, S., Gildehaus, F.J., Ozmen, L., Suárez-Calvet, M., Bartenstein, P., Baumann, K., Ewers, M., Herms, J., Haass, C., Rominger, A.. Increase of TREM2 during aging of an Alzheimer’s disease mouse model is paralleled by microglial activation and amyloidosis. Front. Aging Neurosci.. 2017; 9: 8 [OpenAIRE] [PubMed]

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., Weiner, H.L.. Identification of a unique TGF-β-dependent molecular and functional signature in microglia. Nat. Neurosci.. 2014; 17: 131-143 [OpenAIRE] [PubMed]

Cannon, J.P., O’Driscoll, M., Litman, G.W.. Specific lipid recognition is a general feature of CD300 and TREM molecules. Immunogenetics. 2012; 64: 39-47 [PubMed]

Cantoni, C., Bollman, B., Licastro, D., Xie, M., Mikesell, R., Schmidt, R., Yuede, C.M., Galimberti, D., Olivecrona, G., Klein, R.S., Cross, A.H., Otero, K., Piccio, L.. TREM2 regulates microglial cell activation in response to demyelination in vivo. Acta Neuropathol.. 2015; 129: 429-447 [OpenAIRE] [PubMed]

Carrasquillo, M.M., Allen, M., Burgess, J.D., Wang, X., Strickland, S.L., Aryal, S., Siuda, J., Kachadoorian, M.L., Medway, C., Younkin, C.S., Nair, A., Wang, C., Chanana, P., Serie, D., Nguyen, T., Lincoln, S., Malphrus, K.G., Morgan, K., Golde, T.E., Price, N.D., White, C.C., De Jager, P.L., Bennett, D.A., Asmann, Y.W., Crook, J.E., Petersen, R.C., Graff-Radford, N.R., Dickson, D.W., Younkin, S.G., Ertekin-Taner, N.. A candidate regulatory variant at the TREM gene cluster associates with decreased Alzheimer’s disease risk and increased TREML1 and TREM2 brain gene expression. Alzheimers Dement. 2016; 13: 663-673 [OpenAIRE] [PubMed]

Castranio, E.L., Mounier, A., Wolfe, C.M., Nam, K.N., Fitz, N.F., Letronne, F., Schug, J., Koldamova, R., Lefterov, I.. Gene co-expression networks identify Trem2 and Tyrobp as major hubs in human APOE expressing mice following traumatic brain injury. Neurobiol. Dis.. 2017; 105: 1-14 [OpenAIRE] [PubMed]

Chen, E.Y., Tan, C.M., Kou, Y., Duan, Q., Wang, Z., Meirelles, G.V., Clark, N.R., Ma’ayan, A.. Enrichr: interactive and collaborative HTML5 gene list enrichment analysis tool. BMC Bioinformatics. 2013; 14: 128 [OpenAIRE] [PubMed]

Chertoff, M., Shrivastava, K., Gonzalez, B., Acarin, L., Giménez-Llort, L.. Differential modulation of TREM2 protein during postnatal brain development in mice. PLoS One. 2013; 8: e72083 [OpenAIRE] [PubMed]

Conde, J.R., Streit, W.J.. Microglia in the aging brain. J. Neuropathol. Exp. Neurol.. 2006; 65: 199-203 [PubMed]

Daws, M.R., Sullam, P.M., Niemi, E.C., Chen, T.T., Tchao, N.K., Seaman, W.E.. Pattern recognition by TREM-2: binding of anionic ligands. J. Immunol.. 2003; 171: 594-599 [OpenAIRE] [PubMed]

106 references, page 1 of 8
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publication . Article . Preprint . Other literature type . 2018

Loss of Trem2 in microglia leads to widespread disruption of cell co-expression networks in mouse brain

Carbajosa, Guillermo; Malki, Karim; Lawless, Nathan; Wang, Hong; Ryder, John W.; Wozniak, Eva; Wood, Kristie; Mein, Charles A.; Dobson, Richard J.B.; Collier, David A.; ...