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Small-Molecule-Based Lineage Reprogramming Creates Functional Astrocytes

delete2016-07-01
delete46
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OA
AI
E
Erpo Tian
G
Guoqiang Sun
G
Guihua Sun
J
Jianfei Chao
Y
Ye Peng
C
Charles Warden
A
Arthur D. Riggs
Y
Yanhong Shi *
DOI:10.1016/j.celrep.2016.06.042delete
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摘要

摘要

En 中文
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.
Keyword:
FIBRILLARY ACIDIC PROTEIN
PLURIPOTENT STEM-CELLS
DIRECT CONVERSION
MOUSE FIBROBLASTS
ASTROGLIAL CELLS
NEURONAL CELLS
GENERATION
DISEASE
IDENTIFICATION
EXPRESSION
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期刊

Cell Reports 封面图
Cell Reports
IF:
6.9
论文数:
1.7W
被引数:
10.2W

机构

C
City of Hope
学者数:
9.2K
论文数: 6.5K
被引数: 8.8K
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