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Nat Biomed Eng DOI:10.1038/s41551-018-0219-9

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

Publication TypeJournal Article
Year of Publication2018
AuthorsTekin, H, Simmons, S, Cummings, B, Gao, L, Adiconis, X, Hession, CC, Ghoshal, A, Dionne, D, Choudhury, SR, Yesilyurt, V, Sanjana, NE, Shi, X, Lu, C, Heidenreich, M, Pan, JQ, Levin, JZ, Zhang, F
JournalNat Biomed Eng
Date Published2018 Jul

Understanding neurological diseases requires tractable genetic systems. Engineered 3D neural tissues are an attractive choice, but 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 culturing conditions on the transcriptomic profiles of induced neuronal cells, as well as 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 they correlate with those of specific brain regions and developmental stages. Moreover, by using single-cell sequencing, we show that our engineered tissues recapitulate transcriptional patterns of cell types in the human brain. The analysis of culturing conditions will inform the development of 3D neural tissues for use as tractable models of brain diseases.


Alternate JournalNat Biomed Eng
PubMed ID30271673
PubMed Central IDPMC6157920
Grant ListR01 MH115045 / MH / NIMH NIH HHS / United States
R01 HG009761 / HG / NHGRI NIH HHS / United States
RM1 HG006193 / HG / NHGRI NIH HHS / United States
R01 MH110049 / MH / NIMH NIH HHS / United States
DP1 HL141201 / HL / NHLBI NIH HHS / United States