Effects of 3D culturing conditions on the transcriptomic profile of stem-cell-derived neurons

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 transcri...

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Main Authors: Tekin, Halil, Simmons, Sean, Cummings, Beryl, Gao, Linyi, Adiconis, Xian, Hession, Cynthia C., Ghoshal, Ayan, Dionne, Danielle, Choudhury, Sourav, Yesilyurt, Volkan, Sanjana, Neville E, Shi, Xi, Lu, Congyi, Heidenreich, Matthias, Pan, Jen Q., Levin, Joshua Z., Zhang, Feng
Other Authors: McGovern Institute for Brain Research at MIT
Format: Article
Language:English
Published: Springer Science and Business Media LLC 2020
Online Access:https://hdl.handle.net/1721.1/126476
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author Tekin, Halil
Simmons, Sean
Cummings, Beryl
Gao, Linyi
Adiconis, Xian
Hession, Cynthia C.
Ghoshal, Ayan
Dionne, Danielle
Choudhury, Sourav
Yesilyurt, Volkan
Sanjana, Neville E
Shi, Xi
Lu, Congyi
Heidenreich, Matthias
Pan, Jen Q.
Levin, Joshua Z.
Zhang, Feng
author2 McGovern Institute for Brain Research at MIT
author_facet McGovern Institute for Brain Research at MIT
Tekin, Halil
Simmons, Sean
Cummings, Beryl
Gao, Linyi
Adiconis, Xian
Hession, Cynthia C.
Ghoshal, Ayan
Dionne, Danielle
Choudhury, Sourav
Yesilyurt, Volkan
Sanjana, Neville E
Shi, Xi
Lu, Congyi
Heidenreich, Matthias
Pan, Jen Q.
Levin, Joshua Z.
Zhang, Feng
author_sort Tekin, Halil
collection MIT
description 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.
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spelling mit-1721.1/1264762022-10-03T09:02:37Z Effects of 3D culturing conditions on the transcriptomic profile of stem-cell-derived neurons Tekin, Halil Simmons, Sean Cummings, Beryl Gao, Linyi Adiconis, Xian Hession, Cynthia C. Ghoshal, Ayan Dionne, Danielle Choudhury, Sourav Yesilyurt, Volkan Sanjana, Neville E Shi, Xi Lu, Congyi Heidenreich, Matthias Pan, Jen Q. Levin, Joshua Z. Zhang, Feng 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 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. NIH (Grants 1R01-HG009761, 1R01-MH110049 and 1DP1-HL141201) 2020-08-05T18:19:23Z 2020-08-05T18:19:23Z 2018-04 2017-05 2019-10-08T12:31:13Z Article http://purl.org/eprint/type/JournalArticle 2157-846X https://hdl.handle.net/1721.1/126476 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) en http://dx.doi.org/10.1038/s41551-018-0219-9 Nature Biomedical Engineering 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. application/pdf Springer Science and Business Media LLC PMC
spellingShingle Tekin, Halil
Simmons, Sean
Cummings, Beryl
Gao, Linyi
Adiconis, Xian
Hession, Cynthia C.
Ghoshal, Ayan
Dionne, Danielle
Choudhury, Sourav
Yesilyurt, Volkan
Sanjana, Neville E
Shi, Xi
Lu, Congyi
Heidenreich, Matthias
Pan, Jen Q.
Levin, Joshua Z.
Zhang, Feng
Effects of 3D culturing conditions on the transcriptomic profile of stem-cell-derived neurons
title Effects of 3D culturing conditions on the transcriptomic profile of stem-cell-derived neurons
title_full Effects of 3D culturing conditions on the transcriptomic profile of stem-cell-derived neurons
title_fullStr Effects of 3D culturing conditions on the transcriptomic profile of stem-cell-derived neurons
title_full_unstemmed Effects of 3D culturing conditions on the transcriptomic profile of stem-cell-derived neurons
title_short Effects of 3D culturing conditions on the transcriptomic profile of stem-cell-derived neurons
title_sort effects of 3d culturing conditions on the transcriptomic profile of stem cell derived neurons
url https://hdl.handle.net/1721.1/126476
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