Stem Cell Reports
Volume 10, Issue 3, 13 March 2018, Pages 1016-1029
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Article
Neurons Generated by Mouse ESCs with Hippocampal or Cortical Identity Display Distinct Projection Patterns When Co-transplanted in the Adult Brain

https://doi.org/10.1016/j.stemcr.2018.01.010Get rights and content
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Highlights

  • Wnt signaling induces hippocampal fate in neuralized mouse ESCs

  • Transplanted cortical and hippocampal neurons target distinct regions in adult brain

  • Photothrombotic lesion favors neurite elongation of cortical transplanted cells

  • Cortical cell transplantation improves the motor performance after ischemic damage

Summary

The capability of generating neural precursor cells with distinct types of regional identity in vitro has recently opened new opportunities for cell replacement in animal models of neurodegenerative diseases. By manipulating Wnt and BMP signaling, we steered the differentiation of mouse embryonic stem cells (ESCs) toward isocortical or hippocampal molecular identity. These two types of cells showed different degrees of axonal outgrowth and targeted different regions when co-transplanted in healthy or lesioned isocortex or in hippocampus. In hippocampus, only precursor cells with hippocampal molecular identity were able to extend projections, contacting CA3. Conversely, isocortical-like cells were capable of extending long-range axonal projections only when transplanted in motor cortex, sending fibers toward both intra- and extra-cortical targets. Ischemic damage induced by photothrombosis greatly enhanced the capability of isocortical-like cells to extend far-reaching projections. Our results indicate that neural precursors generated by ESCs carry intrinsic signals specifying axonal extension in different environments.

Keywords

mouse embryonic stem cells
WNT signaling
neuronal identity
transplantation
stroke
cell replacement
isocortex
hippocampus
axonal extension
axonal projection

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Co-senior author