title: hESC-derived Olig2+ progenitors generate a subtype of astroglia with protective effects against ischaemic brain injury.
abstract: Human pluripotent stem cells (hPSCs) have been differentiated to astroglia, but the utilization of hPSC-derived astroglia as cell therapy for neurological diseases has not been well studied. Astroglia are heterogeneous, and not all astroglia are equivalent in promoting neural repair. A prerequisite for cell therapy is to derive defined cell populations with superior therapeutic effects. Here we use an Olig2-GFP human embryonic stem cell (hESC) reporter to demonstrate that hESC-derived Olig2(+) progenitors generate a subtype of previously uncharacterized astroglia (Olig2PC-Astros). These Olig2PC-Astros differ substantially from astroglia differentiated from Olig2-negative hESC-derived neural progenitor cells (NPC-Astros), particularly in their neuroprotective properties. When grafted into brains subjected to global ischaemia, Olig2PC-Astros exhibit superior neuroprotective effects and improved behavioural outcome compared to NPC-Astros. Thus, this new paradigm of human astroglial differentiation is useful for studying the heterogeneity of human astroglia, and the unique Olig2PC-Astros may constitute a new cell therapy for treating cerebral ischaemia and other neurological diseases.
authors.affiliation: Department of Biochemistry and Molecular Medicine, School of Medicine, University of California, Davis, California 95817, USA.
authors.forename: Peng
authors.initials: P
authors.lastname: Jiang
authors.forename: Chen
authors.initials: C
authors.lastname: Chen
authors.forename: Ruimin
authors.initials: R
authors.lastname: Wang
authors.forename: Olga V
authors.initials: OV
authors.lastname: Chechneva
authors.forename: Seung-Hyuk
authors.initials: SH
authors.lastname: Chung
authors.forename: Mahendra S
authors.initials: MS
authors.lastname: Rao
authors.forename: David E
authors.initials: DE
authors.lastname: Pleasure
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.forename: Quanguang
authors.initials: Q
authors.lastname: Zhang
authors.forename: Wenbin
authors.initials: W
authors.lastname: Deng
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology* / Q000378:metabolism / Q000637:transplantation*; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D002545:Brain Ischemia / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D002454:Cell Differentiation; D019070:Cell Lineage; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism; D015870:Gene Expression; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007276:Injections, Intraventricular; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D000076104:Oligodendrocyte Transcription Factor 2; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D013238:Stereotaxic Techniques; D014183:Transplantation, Heterologous
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D015415:Biomarkers; D049452:Green Fluorescent Proteins; D009419:Nerve Tissue Proteins; D000076104:Oligodendrocyte Transcription Factor 2; C405708:OLIG2 protein, human