title: Small-Molecule-Based Lineage Reprogramming Creates Functional Astrocytes.
abstract: Growing evidence indicates important roles for astrocytes in neurodevelopment and diseases. However, astrocytes and their roles in these processes remain poorly understood. Despite recent progress in reprogramming somatic cells into different types of neural cells, reprogramming to astrocytes has lagged. Here, we show that functional astrocytes can be generated from mammalian fibroblasts using only small molecules. Induced mouse astrocytes resemble primary astrocytes in astrocytic gene expression and epigenomic status and exhibit functional properties in promoting neuronal maturation, glutamate uptake, and calcium signaling. Moreover, these cells can recapitulate the Alexander disease phenotype of protein aggregation when expressing Gfap with a disease-causing mutation. The same compounds can also reprogram human fibroblasts into astroglial progenitor cells that can further mature into functional astrocytes. These chemically induced astrocytes may provide cellular models to uncover roles of astrocytes in normal neurodevelopment and pathogenesis of neurological diseases.
authors.affiliation: Division of Stem Cell Biology Research, Department of Developmental and Stem Cell Biology, Beckman Research Institute of City of Hope, 1500 E. Duarte Road, Duarte, CA 91010, USA.
authors.forename: E
authors.initials: E
authors.lastname: Tian
authors.affiliation: Division of Stem Cell Biology Research, Department of Developmental and Stem Cell Biology, Beckman Research Institute of City of Hope, 1500 E. Duarte Road, Duarte, CA 91010, USA.
authors.forename: Guoqiang
authors.initials: G
authors.lastname: Sun
authors.affiliation: Diabetes and Metabolism Research Institute, City of Hope, 1500 E. Duarte Road, Duarte, CA 91010, USA.
authors.forename: Guihua
authors.initials: G
authors.lastname: Sun
authors.affiliation: Division of Stem Cell Biology Research, Department of Developmental and Stem Cell Biology, Beckman Research Institute of City of Hope, 1500 E. Duarte Road, Duarte, CA 91010, USA.
authors.forename: Jianfei
authors.initials: J
authors.lastname: Chao
authors.affiliation: Division of Stem Cell Biology Research, Department of Developmental and Stem Cell Biology, Beckman Research Institute of City of Hope, 1500 E. Duarte Road, Duarte, CA 91010, USA.
authors.forename: Peng
authors.initials: P
authors.lastname: Ye
authors.affiliation: Integrative Genomics Core, Beckman Research Institute of City of Hope, 1500 E. Duarte Road, Duarte, CA 91010, USA.
authors.forename: Charles
authors.initials: C
authors.lastname: Warden
authors.affiliation: Diabetes and Metabolism Research Institute, City of Hope, 1500 E. Duarte Road, Duarte, CA 91010, USA.
authors.forename: Arthur D
authors.initials: AD
authors.lastname: Riggs
authors.affiliation: Division of Stem Cell Biology Research, Department of Developmental and Stem Cell Biology, Beckman Research Institute of City of Hope, 1500 E. Duarte Road, Duarte, CA 91010, USA. Electronic address: yshi@coh.org.
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Shi
mesh_terms: D038261:Alexander Disease / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001253:Astrocytes / Q000378:metabolism / Q000502:physiology*; D020013:Calcium Signaling / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D065150:Cellular Reprogramming / Q000502:physiology*; D018920:Coculture Techniques; D057890:Epigenomics / Q000379:methods; D005347:Fibroblasts / Q000378:metabolism / Q000502:physiology; D015870:Gene Expression / Q000502:physiology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation / Q000502:physiology; D055495:Neurogenesis / Q000502:physiology; D009474:Neurons / Q000378:metabolism / Q000502:physiology; D066263:Protein Aggregation, Pathological / Q000473:pathology; D013234:Stem Cells / Q000378:metabolism / Q000502:physiology
chemical_list: D005904:Glial Fibrillary Acidic Protein; D018698:Glutamic Acid
keywords: Alexander disease; chemical reprogramming; direct conversion; induced astrocytes; small molecules