Dissecting transcriptomic signatures of neuronal differentiation and maturation using iPSCs

Nat Commun. 2020 Jan 23;11(1):462. doi: 10.1038/s41467-019-14266-z.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Animals
  • Astrocytes / cytology
  • Cell Differentiation / genetics*
  • Cells, Cultured
  • Cerebral Cortex / cytology
  • Coculture Techniques
  • Databases, Genetic
  • Gene Expression Regulation
  • Humans
  • Induced Pluripotent Stem Cells / cytology*
  • Induced Pluripotent Stem Cells / physiology*
  • Models, Neurological
  • Neural Stem Cells / cytology
  • Neural Stem Cells / physiology*
  • Neurons / cytology
  • Neurons / physiology
  • Rats
  • Transcriptome*