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Neurogenin-2 Reprograms Human Microglial Lineage Cells into Neurons In Vitro and in Chimeric Brains.

Mengmeng Jin1, Ziyuan Ma1, Rui Dang1

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This summary is machine-generated.

Human microglial cells can be reprogrammed into functional neurons. This discovery offers a new pathway for generating neurons to repair neurological damage and treat brain disorders.

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Area of Science:

  • Neuroscience
  • Stem Cell Biology
  • Regenerative Medicine

Background:

  • Neurological disorders involve progressive neuronal loss, but the adult brain has limited neuron regeneration.
  • Direct neuronal reprogramming is a promising strategy for generating new neurons.
  • Microglia, abundant resident immune cells, possess traits suitable for cellular reprogramming.

Purpose of the Study:

  • To investigate the potential of human microglial lineage cells for neuronal reprogramming.
  • To determine if microglia can be converted into functional neurons.
  • To explore microglia-based strategies for neuronal replacement in neurological disorders.

Main Methods:

  • Utilized live-cell imaging and electrophysiological recordings.
  • Employed inducible NEUROG2 expression in human pluripotent stem cell (hPSC)-derived primitive macrophage progenitors (PMPs) and microglial derivatives.
  • Performed single-nucleus RNA sequencing and xenotransplantation in a human microglia chimeric brain model.

Main Results:

  • hPSC-derived PMPs and microglia successfully acquired neuronal morphology, markers, and synaptic organization.
  • Reprogrammed cells exhibited functional excitability, including action potential firing.
  • Single-nucleus RNA sequencing confirmed a directed lineage conversion from myeloid to neuronal transcriptional programs.
  • In vivo reprogramming of human microglia toward a neuronal identity was demonstrated in a chimeric brain model.

Conclusions:

  • Human microglial lineage cells are a viable substrate for neuronal reprogramming.
  • Inducible NEUROG2 expression effectively drives the conversion of microglia to neurons.
  • This research opens new avenues for microglia-based therapeutic strategies for neuronal replacement and neural repair.