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Related Concept Videos

Introduction to Developmental Psychology01:27

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Developmental psychology explores the changes and continuities in human abilities throughout life, encompassing physical, cognitive, linguistic, and social dimensions. Human development is not restricted to growth, but includes aspects of decline, particularly in physical abilities as individuals age. Developmental psychologists seek to understand how people change as they age and how their mental and social skills evolve.Developmental MilestonesA key concept in developmental psychology is...
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Related Experiment Video

Updated: Feb 9, 2026

Generation of Human Neurons and Oligodendrocytes from Pluripotent Stem Cells for Modeling Neuron-Oligodendrocyte Interactions
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Combining NGN2 Programming with Developmental Patterning Generates Human Excitatory Neurons with NMDAR-Mediated

Ralda Nehme1, Emanuela Zuccaro1, Sulagna Dia Ghosh1

  • 1Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.

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|May 24, 2018
PubMed
Summary

Generating human patterned induced neurons (hpiNs) via NGN2 programming with SMAD and WNT inhibition improves neuronal differentiation. This method yields functional glutamatergic neurons essential for modeling neurological disorders.

Keywords:
AMPARCAMK2ANGN2NMDARWnt inhibitiondual SMAD inhibitionexcitatory neuronshuman stem cellneuronal differentiationsingle cell profiling

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Area of Science:

  • Neuroscience
  • Stem Cell Biology
  • Genetics

Background:

  • Transcription factor programming of pluripotent stem cells (PSCs) is used to generate human neurons for disease modeling.
  • Current methods often yield immature neurons, limiting their use in studying synaptic transmission and neuronal processes.

Purpose of the Study:

  • To develop a method for generating more mature and functional human neurons from PSCs.
  • To improve the utility of induced neurons for modeling nervous system disorders.

Main Methods:

  • Utilized NGN2 programming combined with SMAD and WNT inhibition to generate human patterned induced neurons (hpiNs).
  • Employed single-cell analyses to characterize the differentiation status of hpiN cultures.
  • Used a CAMK2A::GFP reporter gene to identify and select highly differentiated neurons.

Main Results:

  • hpiN cultures displayed a developmental continuum, from progenitors to well-differentiated excitatory glutamatergic neurons.
  • Neurons identified by the CAMK2A::GFP reporter showed enhanced functionality, including NMDAR-mediated synaptic transmission.
  • Single-cell and reporter gene approaches effectively selected for more mature, functional neurons.

Conclusions:

  • Combining NGN2 programming with specific inhibitory factors generates a more developmentally complete population of induced neurons.
  • Reporter gene strategies are crucial for isolating and studying the most functional neurons for disease modeling.
  • These optimized induced neurons significantly enhance the potential for modeling complex nervous system disorders.