ArticleHuman molecular genetics2016
Assessing similarity to primary tissue and cortical layer identity in induced pluripotent stem cell-derived cortical neurons through single-cell transcriptomics.
Article in Human molecular genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers, 1 of them a synthesis that pooled it.
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Who cites it
67 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Building on a Solid Foundation: Adding Relevance and Reproducibility to Neurological Modeling Using Human Pluripotent Stem Cells.Frontiers in cellular neuroscience · 2021Pooled it
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- Reprogramming of neuronal genome function and phenotype by astrocytes.bioRxiv : the preprint server for biology · 2026Article
- Frontotemporal dementia patient-derived iPSC neurons show cell pathological hallmarks and evidence for synaptic dysfunction and DNA damage.Molecular psychiatry · 2026Article
- Decoding exon inclusion in the human brain reveals more divergent splicing mechanisms in neurons than glia.Genome biology · 2026Article
- Joint profiling of cell morphology and gene expression during in vitro neurodevelopment.eLife · 2025Article
- Cerebellar organoids model cell type-specific FOXP2 expression during human cerebellar development.Disease models & mechanisms · 2025Article
- The Neurolipid Atlas: a lipidomics resource for neurodegenerative diseases.Nature metabolism · 2025Article
- Development of MAPT S305 mutation human iPSC lines exhibiting elevated 4R tau expression and functional alterations in neurons and astrocytes.Cell reports · 2024Article
- Consequences of trisomy 21 for brain development in Down syndrome.Nature reviews. Neuroscience · 2024Review
- The Neurolipid Atlas: a lipidomics resource for neurodegenerative diseases uncovers cholesterol as a regulator of astrocyte reactivity impaired by ApoE4.bioRxiv : the preprint server for biology · 2024Article
- Therapeutic validation of MMR-associated genetic modifiers in a human ex vivo model of Huntington disease.American journal of human genetics · 2024Article
- Pluripotent Stem Cells as a Preclinical Cellular Model for Studying Hereditary Spastic Paraplegias.International journal of molecular sciences · 2024Review
- PTCH1-mutant human cerebellar organoids exhibit altered neural development and recapitulate early medulloblastoma tumorigenesis.Disease models & mechanisms · 2024Article
- Tackling neurodegenerationFrontiers in molecular neuroscience · 2024Review
- Neuroimmune mechanisms in autism etiology - untangling a complex problem using human cellular models.Oxford open neuroscience · 2024Article
- Emerging Landscape of Preclinical Models for Studying COVID-19 Neurologic Diseases.ACS pharmacology & translational science · 2023Review
- Multi-omic profiling of the developing human cerebral cortex at the single-cell level.Science advances · 2023Article
- Pioneer factor ASCL1 cooperates with the mSWI/SNF complex at distal regulatory elements to regulate human neural differentiation.Genes & development · 2023Article
7 more citing papers are in PubMed but not listed here.
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15 authors.
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Abstract
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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