Effects of 3D culturing conditions on the transcriptomic profile of stem-cell-derived neurons
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Description
Accepted version
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991.93 KB
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Author(s)
Tekin, Halil
Simmons, Sean
Cummings, Beryl
Gao, Linyi
Adiconis, Xian
Hession, Cynthia C.
Ghoshal, Ayan
Dionne, Danielle
Choudhury, Sourav
Yesilyurt, Volkan
Date Issued
April 2018
Journal
Nature Biomedical Engineering
Publisher
Springer Science and Business Media LLC
Citation
Tekin, Halil et al. "Effects of 3D culturing conditions on the transcriptomic profile of stem-cell-derived neurons." Nature Biomedical Engineering 2, 7 (April 2018): 540–554 © 2018 The Author(s)
Version
Author's final manuscript
Abstract
Understanding neurological diseases requires tractable genetic systems, and engineered three-dimensional (3D) neural tissues are an attractive choice. Yet how the cellular transcriptomic profiles in these tissues are affected by the encapsulating materials and are related to the human brain transcriptome is not well understood. Here, we report the characterization of the effects of different culturing conditions on the transcriptomic profiles of induced neuronal cells and developed a method for the rapid generation of 3D co-cultures of neuronal and astrocytic cells from the same pool of human embryonic stem cells. By comparing the gene-expression profiles of neuronal cells in culture conditions relevant to the developing human brain, we found that modifying the degree of crosslinking of composite hydrogels can tune expression patterns so that they correlate with those of specific brain regions and developmental stages. Moreover, single-cell-sequencing results showed that our engineered tissues recapitulate transcriptional patterns of cell types in the human brain. Analyses of culturing conditions will inform the development of 3D neural tissues for use as tractable models of brain diseases.
MIT Department
McGovern Institute for Brain Research at MIT
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences
Koch Institute for Integrative Cancer Research at MIT
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Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1038/s41551-018-0219-9
