Journal
HUMAN MOLECULAR GENETICS
Volume 25, Issue 5, Pages 989-1000Publisher
OXFORD UNIV PRESS
DOI: 10.1093/hmg/ddv637
Keywords
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Funding
- StemBANCC from Innovative Medicines Initiative [115439]
- European Union
- Wellcome Trust [100643/Z/12/Z, WTISSF121302, 090532/Z/09/Z]
- Oxford Martin School [LC0910-004]
- Monument Trust Discovery Award from Parkinson's UK [2581970, SC037554]
- National Institute for Health Research (NIHR) Oxford Biomedical Research Centre based at Oxford University Hospitals NHS Trust
- University of Oxford
- NIHR Comprehensive Local Research Network
- University of Oxford Wellcome Trust
- Wellcome Trust [100643/Z/12/Z] Funding Source: Wellcome Trust
- MRC [MC_PC_14131, MR/M024962/1, MC_UU_12021/1, MR/M00919X/1, MC_U137761446] Funding Source: UKRI
- Alzheimers Research UK [ARUK-PhD2014-25] Funding Source: researchfish
- Medical Research Council [MR/M00919X/1, MC_U137761446, MC_PC_14131, MR/M024962/1, MC_UU_12021/1] Funding Source: researchfish
- National Institute for Health Research [ACF-2011-18-008] Funding Source: researchfish
- Parkinson's UK [J-1403, J-0901] Funding Source: researchfish
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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. Single-cell multiplex reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) was used to interrogate the expression of genes previously implicated in cortical layer or phenotypic identity in individual cells. Totally, 93.6% of single cells derived from iPSCs expressed genes indicative of neuronal identity. High proportions of single neurons derived from iPSCs expressed glutamatergic receptors and synaptic genes. And, 68.4% of iPSC-derived neurons expressing at least one layer marker could be assigned to a laminar identity using canonical cortical layer marker genes. We compared single-cell RNA-seq of our iPSC-derived neurons to available single-cell RNA-seq data from human fetal and adult brain and found that iPSC-derived cortical neurons closely resembled primary fetal brain cells. Unexpectedly, a subpopulation of iPSC-derived neurons co-expressed canonical fetal deep and upper cortical layer markers. However, this appeared to be concordant with data from primary cells. Our results therefore provide reassurance that iPSC-derived cortical neurons are highly similar to primary cortical neurons at the level of single cells but suggest that current layer markers, although effective, may not be able to disambiguate cortical layer identity in all cells.
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