title: Sporadic ALS Astrocytes Induce Neuronal Degeneration In Vivo.
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.
authors.affiliation: Department of Reproductive Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Qian
authors.affiliation: Department of Rehabilitation Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Hailong
authors.initials: H
authors.lastname: Huang
authors.affiliation: Waisman Center, University of Wisconsin, 1500 Highland Avenue, Madison, WI 53705, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Peterson
authors.affiliation: Waisman Center, University of Wisconsin, 1500 Highland Avenue, Madison, WI 53705, USA.
authors.forename: Baoyang
authors.initials: B
authors.lastname: Hu
authors.affiliation: Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 20036, USA.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Maragakis
authors.affiliation: Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 20036, USA; Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 20036, USA.
authors.forename: Guo-Li
authors.initials: GL
authors.lastname: Ming
authors.affiliation: Department of Rehabilitation Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. Electronic address: chenhong1129@hotmail.com.
authors.forename: Hong
authors.initials: H
authors.lastname: Chen
authors.affiliation: Waisman Center, University of Wisconsin, 1500 Highland Avenue, Madison, WI 53705, USA; Departments of Neuroscience and Neurology, University of Wisconsin, Madison, WI 53705, USA. Electronic address: suchun.zhang@wisc.edu.
authors.forename: Su-Chun
authors.initials: SC
authors.lastname: Zhang
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000473:pathology*; D000818:Animals; D001253:Astrocytes / Q000473:pathology*; D002460:Cell Line; D004195:Disease Models, Animal; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000637:transplantation; D008297:Male; D051379:Mice; D016513:Mice, SCID; D009046:Motor Neurons / Q000473:pathology*; D058953:Neural Stem Cells / Q000473:pathology / Q000637:transplantation; D013116:Spinal Cord / Q000473:pathology*; D013569:Synapses / Q000473:pathology
keywords: amyotrophic lateral sclerosis; astrocytes; cell transplantation; chimera; induced pluripotent stem cells; interneurons; motor neurons; neuron-glial interaction