In vivo reprogramming of astrocytes to neuroblasts in the adult brain.
Adult differentiated cells can be reprogrammed into pluripotent stem cells or lineage-restricted proliferating precursors in culture; however, this has not been demonstrated in vivo. Here, we show that the single transcription factor SOX2 is sufficient to reprogram resident astrocytes into proliferative neuroblasts in the adult mouse brain. These induced adult neuroblasts (iANBs) persist for months and can be generated even in aged brains. When supplied with BDNF and noggin or when the mice are treated with a histone deacetylase inhibitor, iANBs develop into electrophysiologically mature neurons, which functionally integrate into the local neural network. Our results demonstrate that adult astrocytes exhibit remarkable plasticity in vivo, a feature that might have important implications in regeneration of the central nervous system using endogenous patient-specific glial cells.
Department of Molecular Biology, University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, Texas 75390, USA.
Wenze
W
Niu
Tong
T
Zang
Yuhua
Y
Zou
Sanhua
S
Fang
Derek K
DK
Smith
Robert
R
Bachoo
Chun-Li
CL
Zhang
D000818:Animals; D001253:Astrocytes / Q000166:cytology*; D049109:Cell Proliferation; D065150:Cellular Reprogramming / Q000235:genetics*; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D058953:Neural Stem Cells / Q000166:cytology*; D009474:Neurons / Q000166:cytology; D011401:Promoter Regions, Genetic / Q000235:genetics; D055748:SOXB1 Transcription Factors / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
D005904:Glial Fibrillary Acidic Protein; D055748:SOXB1 Transcription Factors; C527783:Sox2 protein, mouse; D014157:Transcription Factors