Expression and function of orphan nuclear receptor TLX in adult neural stem cells

Yanhong Shi, D. Chichung Lie, Philippe Taupin, Kinichi Nakashima, Jasodhara Ray, Ruth T. Yu, Fred H. Gage, Ronald M. Evans

Research output: Contribution to journalArticle

295 Citations (Scopus)

Abstract

The finding of neurogenesis in the adult brain led to the discovery of adult neural stem cells. TLX was initially identified as an orphan nuclear receptor expressed in vertebrate forebrains and is highly expressed in the adult brain. The brains of TLX-null mice have been reported to have no obvious defects during embryogenesis; however, mature mice suffer from retinopathies, severe limbic defects, aggressiveness, reduced copulation and progressively violent behaviour. Here we show that TLX maintains adult neural stem cells in an undifferentiated, proliferative state. We show that TLX-expressing cells isolated by fluorescence-activated cell sorting (FACS) from adult brains can proliferate, self-renew and differentiate into all neural cell types in vitro. By contrast, TLX-null cells isolated from adult mutant brains fail to proliferate. Reintroducing TLX into FACS-sorted TLX-null cells rescues their ability to proliferate and to self-renew. In vivo, TLX mutant mice show a loss of cell proliferation and reduced labelling of nestin in neurogenic areas in the adult brain. TLX can silence glia-specific expression of the astrocyte marker GFAP in neural stem cells, suggesting that transcriptional repression may be crucial in maintaining the undifferentiated state of these cells.

Original languageEnglish
Pages (from-to)78-83
Number of pages6
JournalNature
Volume427
Issue number6969
DOIs
Publication statusPublished - Jan 1 2004
Externally publishedYes

Fingerprint

Orphan Nuclear Receptors
Adult Stem Cells
Neural Stem Cells
Brain
Null Lymphocytes
Flow Cytometry
Copulation
Nestin
Aptitude
Neurogenesis
Prosencephalon
Neuroglia
Astrocytes
Embryonic Development
Vertebrates
Cell Proliferation

All Science Journal Classification (ASJC) codes

  • General

Cite this

Shi, Y., Lie, D. C., Taupin, P., Nakashima, K., Ray, J., Yu, R. T., ... Evans, R. M. (2004). Expression and function of orphan nuclear receptor TLX in adult neural stem cells. Nature, 427(6969), 78-83. https://doi.org/10.1038/nature02211

Expression and function of orphan nuclear receptor TLX in adult neural stem cells. / Shi, Yanhong; Lie, D. Chichung; Taupin, Philippe; Nakashima, Kinichi; Ray, Jasodhara; Yu, Ruth T.; Gage, Fred H.; Evans, Ronald M.

In: Nature, Vol. 427, No. 6969, 01.01.2004, p. 78-83.

Research output: Contribution to journalArticle

Shi, Y, Lie, DC, Taupin, P, Nakashima, K, Ray, J, Yu, RT, Gage, FH & Evans, RM 2004, 'Expression and function of orphan nuclear receptor TLX in adult neural stem cells', Nature, vol. 427, no. 6969, pp. 78-83. https://doi.org/10.1038/nature02211
Shi, Yanhong ; Lie, D. Chichung ; Taupin, Philippe ; Nakashima, Kinichi ; Ray, Jasodhara ; Yu, Ruth T. ; Gage, Fred H. ; Evans, Ronald M. / Expression and function of orphan nuclear receptor TLX in adult neural stem cells. In: Nature. 2004 ; Vol. 427, No. 6969. pp. 78-83.
@article{41e2c3c655b4413dbb4dd3d9ae8c5c2b,
title = "Expression and function of orphan nuclear receptor TLX in adult neural stem cells",
abstract = "The finding of neurogenesis in the adult brain led to the discovery of adult neural stem cells. TLX was initially identified as an orphan nuclear receptor expressed in vertebrate forebrains and is highly expressed in the adult brain. The brains of TLX-null mice have been reported to have no obvious defects during embryogenesis; however, mature mice suffer from retinopathies, severe limbic defects, aggressiveness, reduced copulation and progressively violent behaviour. Here we show that TLX maintains adult neural stem cells in an undifferentiated, proliferative state. We show that TLX-expressing cells isolated by fluorescence-activated cell sorting (FACS) from adult brains can proliferate, self-renew and differentiate into all neural cell types in vitro. By contrast, TLX-null cells isolated from adult mutant brains fail to proliferate. Reintroducing TLX into FACS-sorted TLX-null cells rescues their ability to proliferate and to self-renew. In vivo, TLX mutant mice show a loss of cell proliferation and reduced labelling of nestin in neurogenic areas in the adult brain. TLX can silence glia-specific expression of the astrocyte marker GFAP in neural stem cells, suggesting that transcriptional repression may be crucial in maintaining the undifferentiated state of these cells.",
author = "Yanhong Shi and Lie, {D. Chichung} and Philippe Taupin and Kinichi Nakashima and Jasodhara Ray and Yu, {Ruth T.} and Gage, {Fred H.} and Evans, {Ronald M.}",
year = "2004",
month = "1",
day = "1",
doi = "10.1038/nature02211",
language = "English",
volume = "427",
pages = "78--83",
journal = "Nature",
issn = "0028-0836",
publisher = "Nature Publishing Group",
number = "6969",

}

TY - JOUR

T1 - Expression and function of orphan nuclear receptor TLX in adult neural stem cells

AU - Shi, Yanhong

AU - Lie, D. Chichung

AU - Taupin, Philippe

AU - Nakashima, Kinichi

AU - Ray, Jasodhara

AU - Yu, Ruth T.

AU - Gage, Fred H.

AU - Evans, Ronald M.

PY - 2004/1/1

Y1 - 2004/1/1

N2 - The finding of neurogenesis in the adult brain led to the discovery of adult neural stem cells. TLX was initially identified as an orphan nuclear receptor expressed in vertebrate forebrains and is highly expressed in the adult brain. The brains of TLX-null mice have been reported to have no obvious defects during embryogenesis; however, mature mice suffer from retinopathies, severe limbic defects, aggressiveness, reduced copulation and progressively violent behaviour. Here we show that TLX maintains adult neural stem cells in an undifferentiated, proliferative state. We show that TLX-expressing cells isolated by fluorescence-activated cell sorting (FACS) from adult brains can proliferate, self-renew and differentiate into all neural cell types in vitro. By contrast, TLX-null cells isolated from adult mutant brains fail to proliferate. Reintroducing TLX into FACS-sorted TLX-null cells rescues their ability to proliferate and to self-renew. In vivo, TLX mutant mice show a loss of cell proliferation and reduced labelling of nestin in neurogenic areas in the adult brain. TLX can silence glia-specific expression of the astrocyte marker GFAP in neural stem cells, suggesting that transcriptional repression may be crucial in maintaining the undifferentiated state of these cells.

AB - The finding of neurogenesis in the adult brain led to the discovery of adult neural stem cells. TLX was initially identified as an orphan nuclear receptor expressed in vertebrate forebrains and is highly expressed in the adult brain. The brains of TLX-null mice have been reported to have no obvious defects during embryogenesis; however, mature mice suffer from retinopathies, severe limbic defects, aggressiveness, reduced copulation and progressively violent behaviour. Here we show that TLX maintains adult neural stem cells in an undifferentiated, proliferative state. We show that TLX-expressing cells isolated by fluorescence-activated cell sorting (FACS) from adult brains can proliferate, self-renew and differentiate into all neural cell types in vitro. By contrast, TLX-null cells isolated from adult mutant brains fail to proliferate. Reintroducing TLX into FACS-sorted TLX-null cells rescues their ability to proliferate and to self-renew. In vivo, TLX mutant mice show a loss of cell proliferation and reduced labelling of nestin in neurogenic areas in the adult brain. TLX can silence glia-specific expression of the astrocyte marker GFAP in neural stem cells, suggesting that transcriptional repression may be crucial in maintaining the undifferentiated state of these cells.

UR - http://www.scopus.com/inward/record.url?scp=0347719238&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0347719238&partnerID=8YFLogxK

U2 - 10.1038/nature02211

DO - 10.1038/nature02211

M3 - Article

C2 - 14702088

AN - SCOPUS:0347719238

VL - 427

SP - 78

EP - 83

JO - Nature

JF - Nature

SN - 0028-0836

IS - 6969

ER -