Multi-Parametric Profiling Network Based on Gene Expression and Phenotype Data: A Novel Approach to Developmental Neurotoxicity Testing
Abstract
:1. Introduction
2. Results and Discussion
2.1. Phenotype Profiling Based on the Morphology of Differentiated Neuronal Cells by High-Content Image Analysis and Generation of Phenotypic Networks
2.2. Generation of a Comprehensive Network Based on Gene Expression and Phenotype Profiling by a Bayesian Network Model
2.3. Classification of Chemicals Based on the Values of the Parameters of the Comprehensive Networks
2.4. Discussion for Future Work
3. Experimental Section
3.1. Selection of Test Chemicals
3.2. Design of Multi-Parametric Profiling Networks Analysis for Detecting Developmental Neuronal Toxicity of Chemicals That Effects Fetal Programming
3.3. mESC Culture and Maintenance
3.4. EB Formation from mESC and Chemical Treatment
3.5. Immunofluorescence
3.6. Morphological Analysis of mESC, EB and Neuronal Cell Lineages
3.7. Gene Expression Analysis and Creation of Candidate Gene Sets
3.8. Gene and Morphology Interaction Network Analysis
3.9. Statistical Analysis
4. Conclusions
Acknowledgments
References
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Chemical Name | Ellipsis | Intended Use | Physiological Effect and Toxicity | Mode of Action | Target Protein |
---|---|---|---|---|---|
Triiodotyronine | T3 | Endogenenous hormne | Pseudo thyroid hormone | transcriptional regulation | Thyroid hormone receptor (TR)α, TRβ |
Dexamethazone | DEX | Medicinal drug | Pseudo corticosteroid hormone | transcriptional regulation | Glucocorticoid receptor (GR) |
17b-Estradiol | E2 | Endogenenous hormne | transcriptional regulation | Estrogen receptor (ER)α, ERβ | |
5a-Dihydrotestosterone | DHT | Endogenenous hormne | transcriptional regulation | Androgen receptor (AR) | |
2,3,7,8-tetrachlorodibenzo-p-dioxin | TCDD | Unintentional chemical | Multi-toxicity | transcriptional regulation | Aryl hydrocarbon receptor (AhR) |
Methoprene acid | MPA | Pesticides | Teretogenecity | transcriptional regulation | Retinoid X receptor (RXR)α, RXRβ, RXRγ |
Cyclopamine | CPM | Medicinal drug | Teretogenecity | Signal inhibition | Hadgehog signaling pathway |
Thalidmide | TMD | Medicinal drug | Teretogenecity and Autism | Unknown | Oxidative stress |
4(OH)-2′,3,3′,4′,5′-pentachlorobephenyl 107 | PCB | Metabolite of PBC | Multi-toxicity | Unknown | Unknown (ERα, oxidativestress) |
Permethrin | PMT | Pesticides | Neuro-toxicity | Unknown | Oxidative stress |
Bisphenol A | BPA | Plastic materials | Reproductive and Neuro-toxicity? | Unknown | Unknown (ERα, ERRγ) |
Bis(2-ethylhexyl) phthalate | DEHP | Plastic materials | Reproductive and Neuro-toxicity? | Unknown | Unknown [Peroxisome proliferator-activated receptor (PPAR)α, antiTR] |
Alzheimer | Autism | Parkinson | Axon Guidance | Pluripotent | Neural Development | Oxidative-Stress |
---|---|---|---|---|---|---|
AR | AR | AR | 1500003O03Rik | Arid3b | Atbf1 | Aass |
ApoE | Cntnap2 | Casp3 | Abl1 | Esrrb | Cdyl | Als2 |
App | En2 | Casp7 | Ablim1 | Fkbp3 | Fos | Apoe |
Bace | Esr1 | Casp9 | Cfl1 | Hdac2 | Gbx2 | Ctsb |
Casp3 | Esr2 | Esr1 | Cxcl12 | Klf4 | Gfap | Dnm2 |
Casp7 | Fmr1 | Esr2 | Efna4 | Mybbp1a | Hras1 | Fancc |
Esr1 | Foxp2 | Park2 | Epha2 | Nacc1 | Map2 | Gpx7 |
Esr2 | Gabrb3 | Park7 | Ephb1 | Nanog | Mapk1 | Gpx8 |
Ide | Mecp2 | RARa | Nfatc2 | Nfkbib | Mapk3 | Gusb |
Il1r1 | Nlgn3 | RARb | Nfatc3 | Nr0b1 | Nestin | Hprt1 |
Mme | RARa | RARg | Ntng1 | Nr5a2 | Pla2g6 | Kif9 |
Psen | RARb | Slc6a3 | Sema3a | Pou5f1 | Raf1 | Noxo1 |
RARa | RARg | Snca | Sema3b | Rex1 | Rhog | Nxn |
RARb | Reln | Th | Sema3d | Sall4 | Rif1 | Park7 |
RARg | Slc6a4 | Uchl1 | Sema3f | Smarcad1 | Rps6ka1 | Ppp1r15b |
Tnfrsf1a | Tsc1 | Sema3g | Smarcc1 | Sall1 | Prdx2 | |
Tsc2 | Sema6a | Sox2 | Shc1 | Prdx6-rs1 | ||
Ube3a | Sema6b | Sp1 | Smarcad1 | Psmb5 | ||
Sema6d | Spag1 | Sox2 | Recql4 | |||
Srgap3 | Trim28 | Tuj1 | Scd1 | |||
Unc5d | Zfp281 | Map2k1 | Slc41a3 | |||
c-Myc | Sod1 | |||||
Sod3 | ||||||
Txnip | ||||||
Txnrd1 | ||||||
Xpa |
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Nagano, R.; Akanuma, H.; Qin, X.-Y.; Imanishi, S.; Toyoshiba, H.; Yoshinaga, J.; Ohsako, S.; Sone, H. Multi-Parametric Profiling Network Based on Gene Expression and Phenotype Data: A Novel Approach to Developmental Neurotoxicity Testing. Int. J. Mol. Sci. 2012, 13, 187-207. https://doi.org/10.3390/ijms13010187
Nagano R, Akanuma H, Qin X-Y, Imanishi S, Toyoshiba H, Yoshinaga J, Ohsako S, Sone H. Multi-Parametric Profiling Network Based on Gene Expression and Phenotype Data: A Novel Approach to Developmental Neurotoxicity Testing. International Journal of Molecular Sciences. 2012; 13(1):187-207. https://doi.org/10.3390/ijms13010187
Chicago/Turabian StyleNagano, Reiko, Hiromi Akanuma, Xian-Yang Qin, Satoshi Imanishi, Hiroyoshi Toyoshiba, Jun Yoshinaga, Seiichiroh Ohsako, and Hideko Sone. 2012. "Multi-Parametric Profiling Network Based on Gene Expression and Phenotype Data: A Novel Approach to Developmental Neurotoxicity Testing" International Journal of Molecular Sciences 13, no. 1: 187-207. https://doi.org/10.3390/ijms13010187