Small-Molecule-Based Lineage Reprogramming Creates Functional Astrocytes

Citations Over TimeTop 10% of 2016 papers

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.

Related Papers

• → Purification of functional reprogramming factors in mammalian cell using FLAG -Tag(2017)7 cited
• → Generation of Induced Pluripotent Stem Cells(2014)16 cited
• → Application of Patient-Specific Induced Pluripotent Stem Cells Produced by Somatic Cells Reprogramming for Treatment of Neurodegenerative Diseases(2013)5 cited
• → Generation of Induced Pluripotent Stem Cells(2020)1 cited
• → Progress in the reprogramming of induced pluripotent stem cells with small molecules(2015)