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| Status |
Public on Sep 08, 2015 |
| Title |
Human pluripotent stem cell-derived neural constructs for predictive neurotoxicity screening |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Human pluripotent stem cell-based in vitro models that reflect human physiology have the potential to reduce the number of drug failures in clinical trials, and offer a cost effective approach for assessing chemical safety. Here, human embryonic stem (ES) cell-derived neural progenitor cells, endothelial cells, mesenchymal stem cells, and microglia/macrophage precursors were combined on chemically-defined poly(ethylene glycol) (PEG) hydrogels and cultured in serum-free media to model cellular interactions of the developing brain. The precursors self-assembled into 3-dimensional (3D) neural constructs with cortically organized neuronal and glial cells, interconnected vascular networks, and ramified microglia. Replicate constructs were highly reproducible by RNA sequencing (Spearman’s correlation coefficients, ρ ≥ 0.97) and robustly expressed neurogenesis, vasculature development, and microglia genes. Finally, linear support vector machines were used to construct a predictive model from RNA sequencing data for 240 neural constructs treated with 60 toxic and non-toxic chemicals, which then correctly classified 9/10 blinded compounds.
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| Overall design |
Note that all cell types were derived from the H1 human embryonic stem cell line. 11 samples for initial quality control (triplicate day 13 neural progenitor cells; quadruplicate day 21 neural progenitor cells cocultured with mesenchymal stem cells and endothelial cells; quadruplicate day 21 neural progenitor cells cocultured with mesenchymal stem cells and endothelial cells and migroglia/macrophage precursor cells), quadruplicate samples of H1 ES cells as a control for comparing to untreated toxicity study samples, and 288 samples associated with toxicity screening (all samples formed using neural progenitor cells, endothelial cells, mesenchymal stem cells, and microglia/macrophage precursors).
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| Contributor(s) |
Schwartz MP, Hou Z, Propson NE, Zhang J, Costa VS, Jiang P, Nguyen BK, Bolin JM, Engstrom C, Daly W, Wang Y, Stewart R, Page CD, Murphy WL, Thomson JA |
| Citation(s) |
26392547, 28599598 |
| Submission date |
Dec 06, 2014 |
| Last update date |
Jun 11, 2019 |
| Contact name |
Peng Jiang |
| E-mail(s) |
p.jiang@csuohio.edu
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| Organization name |
Cleveland State University
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| Street address |
2121 Euclid Ave
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| City |
Cleveland |
| State/province |
OH |
| ZIP/Postal code |
44115 |
| Country |
USA |
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| Platforms (1) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
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| Samples (303)
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| Relations |
| BioProject |
PRJNA269573 |
| SRA |
SRP050892 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE63935_Schwartz_PNAS_PUBLISHED_Datasets_S01_08_GEO.xlsx |
41.6 Mb |
(ftp)(http) |
XLSX |
SRA Run Selector |
| Processed data are available on Series record |
| Raw data are available in SRA |
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