Dataset Information

Dissecting transcriptomic signatures of neuronal differentiation and maturation using iPSCs.

ABSTRACT: Human induced pluripotent stem cells (hiPSCs) are a powerful model of neural differentiation and maturation. We present a hiPSC transcriptomics resource on corticogenesis from 5 iPSC donor and 13 subclonal lines across 9 time points over 5 broad conditions: self-renewal, early neuronal differentiation, neural precursor cells (NPCs), assembled rosettes, and differentiated neuronal cells. We identify widespread changes in the expression of both individual features and global patterns of transcription. We next demonstrate that co-culturing human NPCs with rodent astrocytes results in mutually synergistic maturation, and that cell type-specific expression data can be extracted using only sequencing read alignments without cell sorting. We lastly adapt a previously generated RNA deconvolution approach to single-cell expression data to estimate the relative neuronal maturity of iPSC-derived neuronal cultures and human brain tissue. Using many public datasets, we demonstrate neuronal cultures are maturationally heterogeneous but contain subsets of neurons more mature than previously observed.

SUBMITTER: Burke EE

PROVIDER: S-EPMC6978526 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Dissecting transcriptomic signatures of neuronal differentiation and maturation using iPSCs.

Burke Emily E EE Chenoweth Joshua G JG Shin Joo Heon JH Collado-Torres Leonardo L Kim Suel-Kee SK Micali Nicola N Wang Yanhong Y Colantuoni Carlo C Straub Richard E RE Hoeppner Daniel J DJ Chen Huei-Ying HY Sellers Alana A Shibbani Kamel K Hamersky Gregory R GR Diaz Bustamante Marcelo M Phan BaDoi N BN Ulrich William S WS Valencia Cristian C Jaishankar Amritha A Price Amanda J AJ Rajpurohit Anandita A Semick Stephen A SA Bürli Roland W RW Barrow James C JC Hiler Daniel J DJ Page Stephanie C SC Martinowich Keri K Hyde Thomas M TM Kleinman Joel E JE Berman Karen F KF Apud Jose A JA Cross Alan J AJ Brandon Nicholas J NJ Weinberger Daniel R DR Maher Brady J BJ McKay Ronald D G RDG Jaffe Andrew E AE

Nature communications 20200123 1

Human induced pluripotent stem cells (hiPSCs) are a powerful model of neural differentiation and maturation. We present a hiPSC transcriptomics resource on corticogenesis from 5 iPSC donor and 13 subclonal lines across 9 time points over 5 broad conditions: self-renewal, early neuronal differentiation, neural precursor cells (NPCs), assembled rosettes, and differentiated neuronal cells. We identify widespread changes in the expression of both individual features and global patterns of transcript ...[more]

PMID: 31974374

Similar Datasets

Project description:Genes for autism spectrum disorders (ASDs) are also implicated in fragile X syndrome (FXS), intellectual disabilities (ID) or schizophrenia (SCZ), and converge on neuronal function and differentiation. The SH-SY5Y neuroblastoma cell line, the most widely used system to study neurodevelopment, is currently discussed for its applicability to model cortical development. We implemented an optimal neuronal differentiation protocol of this system and evaluated neurodevelopment at the transcriptomic level using the CoNTeXT framework, a machine-learning algorithm based on human post-mortem brain data estimating developmental stage and regional identity of transcriptomic signatures. Our improved model in contrast to currently used SH-SY5Y models does capture early neurodevelopmental processes with high fidelity. We applied regression modelling, dynamic time warping analysis, parallel independent component analysis and weighted gene co-expression network analysis to identify activated gene sets and networks. Finally, we tested and compared these sets for enrichment of risk genes for neuropsychiatric disorders. We confirm a significant overlap of genes implicated in ASD with FXS, ID and SCZ. However, counterintuitive to this observation, we report that risk genes affect pathways specific for each disorder during early neurodevelopment. Genes implicated in ASD, ID, FXS and SCZ were enriched among the positive regulators, but only ID-implicated genes were also negative regulators of neuronal differentiation. ASD and ID genes were involved in dendritic branching modules, but only ASD risk genes were implicated in histone modification or axonal guidance. Only ID genes were over-represented among cell cycle modules. We conclude that the underlying signatures are disorder-specific and that the shared genetic architecture results in overlaps across disorders such as ID in ASD. Thus, adding developmental network context to genetic analyses will aid differentiating the pathophysiology of neuropsychiatric disorders.

Dataset Information

Dissecting transcriptomic signatures of neuronal differentiation and maturation using iPSCs.

Publications

Dissecting transcriptomic signatures of neuronal differentiation and maturation using iPSCs.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets