Unknown,Transcriptomics,Genomics,Proteomics

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Single cell transcriptomics analysis of induced pluripotent stem cell-derived cortical neurons reveals frequent dual layer identity

ABSTRACT: Induced pluripotent stem cell (iPSC)-derived cortical neurons present a powerful new model of neurological disease. Previous work has established that differentiation protocols produce cortical neurons but little has been done to characterise these at cellular resolution. In particular, it is unclear to what extent in vitro two-dimensional, relatively disordered culture conditions recapitulate the development of in vivo cortical layer identity. Single cell multiplex RT-qPCR was used to interrogate the expression of genes previously implicated in cortical layer or phenotypic identity in individual cells. Unexpectedly, 22.7% of neurons analysed frequently co-expressed canonical fetal deep and upper cortical layer markers, and this co-expression was also present at the level of translated protein. By comparing our results to available single cell RNA-seq data from human fetal and adult brain, we observed that this co-expression of layer markers was also seen in primary tissue. These results suggest that establishing neuronal layer identity in iPSC-derived or primary cortical neurons using canonical marker genes transcripts is unlikely to be informative. Single cell RNA-seq of 16 iPSC-derived cortical neurons. This dataset was used for normalization purposes for GSE67835.

ORGANISM(S): Homo sapiens

SUBMITTER: Adam Handel

PROVIDER: E-GEOD-69790 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Assessing similarity to primary tissue and cortical layer identity in induced pluripotent stem cell-derived cortical neurons through single-cell transcriptomics.

Handel Adam E AE Chintawar Satyan S Lalic Tatjana T Whiteley Emma E Vowles Jane J Giustacchini Alice A Argoud Karene K Sopp Paul P Nakanishi Mahito M Bowden Rory R Cowley Sally S Newey Sarah S Akerman Colin C Ponting Chris P CP Cader M Zameel MZ

Human molecular genetics 20160105 5

Induced pluripotent stem cell (iPSC)-derived cortical neurons potentially present a powerful new model to understand corticogenesis and neurological disease. Previous work has established that differentiation protocols can produce cortical neurons, but little has been done to characterize these at cellular resolution. In particular, it is unclear to what extent in vitro two-dimensional, relatively disordered culture conditions recapitulate the development of in vivo cortical layer identity. Sing ...[more]

PMID: 26740550

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