Sporadic ALS Astrocytes Induce Neuronal Degeneration In Vivo

Kun Qian, Hailong Huang, Andrew Peterson, Baoyang Hu, Nicholas J. Maragakis, Guo li Ming, Hong Chen, Su Chun Zhang

Research output: Contribution to journalArticlepeer-review

Abstract

Astrocytes from familial amyotrophic lateral sclerosis (ALS) patients or transgenic mice are toxic specifically to motor neurons (MNs). It is not known if astrocytes from sporadic ALS (sALS) patients cause MN degeneration in vivo and whether the effect is specific to MNs. By transplanting spinal neural progenitors, derived from sALS and healthy induced pluripotent stem cells (iPSCs), into the cervical spinal cord of adult SCID mice for 9 months, we found that differentiated human astrocytes were present in large areas of the spinal cord, replaced endogenous astrocytes, and contacted neurons to a similar extent. Mice with sALS but not non-ALS cells showed reduced non-MNs numbers followed by MNs in the host spinal cord. The surviving MNs showed reduced inputs from inhibitory neurons and exhibited disorganized neurofilaments and aggregated ubiquitin. Correspondingly, mice with sALS but not non-ALS cells showed declined movement deficits. Thus, sALS iPSC-derived astrocytes cause ALS-like degeneration in both MNs and non-MNs.

Original languageEnglish (US)
Pages (from-to)843-855
Number of pages13
JournalStem Cell Reports
Volume8
Issue number4
DOIs
StatePublished - Apr 11 2017

Keywords

  • amyotrophic lateral sclerosis
  • astrocytes
  • cell transplantation
  • chimera
  • induced pluripotent stem cells
  • interneurons
  • motor neurons
  • neuron-glial interaction

ASJC Scopus subject areas

  • Biochemistry
  • Genetics
  • Developmental Biology
  • Cell Biology

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