Identification of astrocyte-expressed factors that modulate neural stem/progenitor cell differentiation

Basam Z. Barkho, Hongjun Song, James B. Aimone, Richard D. Smrt, Tomoko Kuwabara, Kinichi Nakashima, Fred H. Gage, Xinyu Zhao

Research output: Contribution to journalArticle

204 Citations (Scopus)

Abstract

Multipotent neural stem/progenitor cells (NSPCs) can be isolated from many regions of the adult central nervous system (CNS), yet neurogenesis is restricted to the hippocampus and subventricular zone in vivo. Identification of the molecular cues that modulate NSPC fate choice is a prerequisite for their therapeutic applications. Previously, we demonstrated that primary astrocytes isolated from regions with higher neuroplasticity, such as newborn and adult hippocampus and newborn spinal cord, promoted neuronal differentiation of adult NSPCs, whereas astrocytes isolated from the nonneurogenic region of the adult spinal cord inhibited neural differentiation. To identify the factors expressed by these astrocytes that could modulate NSPC differentiation, we performed gene expression profiling analysis using Affymetrix rat genome arrays. Our results demonstrated that these astrocytes had distinct gene expression profiles. We further tested the functional effects of candidate factors that were differentially expressed in neurogenesis-promoting and -inhibiting astrocytes using in vitro NSPC differentiation assays. Our results indicated that two interleukins, IL-1/3 and IL-6, and a combination of factors that included these two interleukins could promote NSPC neuronal differentiation, whereas insulin-like growth factor binding protein 6 (IGFBP6) and decorin inhibited neuronal differentiation of adult NSPCs. Our results have provided further evidence to support the ongoing hypothesis that, in adult mammalian brains, astrocytes play critical roles in modulating NSPC differentiation. The finding that cytokines and chemokines expressed by astrocytes could promote NSPC neuronal differentiation may help us to understand how injuries induce neurogenesis in adult brains.

Original languageEnglish
Pages (from-to)407-421
Number of pages15
JournalStem Cells and Development
Volume15
Issue number3
DOIs
Publication statusPublished - Jun 1 2006
Externally publishedYes

Fingerprint

Neural Stem Cells
Astrocytes
Cell Differentiation
Stem Cells
Neurogenesis
Adult Stem Cells
Interleukin-1
Hippocampus
Spinal Cord
Insulin-Like Growth Factor Binding Protein 6
Multipotent Stem Cells
Decorin
Neuronal Plasticity
Interleukin-3
Lateral Ventricles
Interleukins
Brain
Gene Expression Profiling
Transcriptome
Chemokines

All Science Journal Classification (ASJC) codes

  • Hematology
  • Developmental Biology
  • Cell Biology

Cite this

Identification of astrocyte-expressed factors that modulate neural stem/progenitor cell differentiation. / Barkho, Basam Z.; Song, Hongjun; Aimone, James B.; Smrt, Richard D.; Kuwabara, Tomoko; Nakashima, Kinichi; Gage, Fred H.; Zhao, Xinyu.

In: Stem Cells and Development, Vol. 15, No. 3, 01.06.2006, p. 407-421.

Research output: Contribution to journalArticle

Barkho, Basam Z. ; Song, Hongjun ; Aimone, James B. ; Smrt, Richard D. ; Kuwabara, Tomoko ; Nakashima, Kinichi ; Gage, Fred H. ; Zhao, Xinyu. / Identification of astrocyte-expressed factors that modulate neural stem/progenitor cell differentiation. In: Stem Cells and Development. 2006 ; Vol. 15, No. 3. pp. 407-421.
@article{e5494d67e1c24861afd83731c028381f,
title = "Identification of astrocyte-expressed factors that modulate neural stem/progenitor cell differentiation",
abstract = "Multipotent neural stem/progenitor cells (NSPCs) can be isolated from many regions of the adult central nervous system (CNS), yet neurogenesis is restricted to the hippocampus and subventricular zone in vivo. Identification of the molecular cues that modulate NSPC fate choice is a prerequisite for their therapeutic applications. Previously, we demonstrated that primary astrocytes isolated from regions with higher neuroplasticity, such as newborn and adult hippocampus and newborn spinal cord, promoted neuronal differentiation of adult NSPCs, whereas astrocytes isolated from the nonneurogenic region of the adult spinal cord inhibited neural differentiation. To identify the factors expressed by these astrocytes that could modulate NSPC differentiation, we performed gene expression profiling analysis using Affymetrix rat genome arrays. Our results demonstrated that these astrocytes had distinct gene expression profiles. We further tested the functional effects of candidate factors that were differentially expressed in neurogenesis-promoting and -inhibiting astrocytes using in vitro NSPC differentiation assays. Our results indicated that two interleukins, IL-1/3 and IL-6, and a combination of factors that included these two interleukins could promote NSPC neuronal differentiation, whereas insulin-like growth factor binding protein 6 (IGFBP6) and decorin inhibited neuronal differentiation of adult NSPCs. Our results have provided further evidence to support the ongoing hypothesis that, in adult mammalian brains, astrocytes play critical roles in modulating NSPC differentiation. The finding that cytokines and chemokines expressed by astrocytes could promote NSPC neuronal differentiation may help us to understand how injuries induce neurogenesis in adult brains.",
author = "Barkho, {Basam Z.} and Hongjun Song and Aimone, {James B.} and Smrt, {Richard D.} and Tomoko Kuwabara and Kinichi Nakashima and Gage, {Fred H.} and Xinyu Zhao",
year = "2006",
month = "6",
day = "1",
doi = "10.1089/scd.2006.15.407",
language = "English",
volume = "15",
pages = "407--421",
journal = "Stem Cells and Development",
issn = "1547-3287",
publisher = "Mary Ann Liebert Inc.",
number = "3",

}

TY - JOUR

T1 - Identification of astrocyte-expressed factors that modulate neural stem/progenitor cell differentiation

AU - Barkho, Basam Z.

AU - Song, Hongjun

AU - Aimone, James B.

AU - Smrt, Richard D.

AU - Kuwabara, Tomoko

AU - Nakashima, Kinichi

AU - Gage, Fred H.

AU - Zhao, Xinyu

PY - 2006/6/1

Y1 - 2006/6/1

N2 - Multipotent neural stem/progenitor cells (NSPCs) can be isolated from many regions of the adult central nervous system (CNS), yet neurogenesis is restricted to the hippocampus and subventricular zone in vivo. Identification of the molecular cues that modulate NSPC fate choice is a prerequisite for their therapeutic applications. Previously, we demonstrated that primary astrocytes isolated from regions with higher neuroplasticity, such as newborn and adult hippocampus and newborn spinal cord, promoted neuronal differentiation of adult NSPCs, whereas astrocytes isolated from the nonneurogenic region of the adult spinal cord inhibited neural differentiation. To identify the factors expressed by these astrocytes that could modulate NSPC differentiation, we performed gene expression profiling analysis using Affymetrix rat genome arrays. Our results demonstrated that these astrocytes had distinct gene expression profiles. We further tested the functional effects of candidate factors that were differentially expressed in neurogenesis-promoting and -inhibiting astrocytes using in vitro NSPC differentiation assays. Our results indicated that two interleukins, IL-1/3 and IL-6, and a combination of factors that included these two interleukins could promote NSPC neuronal differentiation, whereas insulin-like growth factor binding protein 6 (IGFBP6) and decorin inhibited neuronal differentiation of adult NSPCs. Our results have provided further evidence to support the ongoing hypothesis that, in adult mammalian brains, astrocytes play critical roles in modulating NSPC differentiation. The finding that cytokines and chemokines expressed by astrocytes could promote NSPC neuronal differentiation may help us to understand how injuries induce neurogenesis in adult brains.

AB - Multipotent neural stem/progenitor cells (NSPCs) can be isolated from many regions of the adult central nervous system (CNS), yet neurogenesis is restricted to the hippocampus and subventricular zone in vivo. Identification of the molecular cues that modulate NSPC fate choice is a prerequisite for their therapeutic applications. Previously, we demonstrated that primary astrocytes isolated from regions with higher neuroplasticity, such as newborn and adult hippocampus and newborn spinal cord, promoted neuronal differentiation of adult NSPCs, whereas astrocytes isolated from the nonneurogenic region of the adult spinal cord inhibited neural differentiation. To identify the factors expressed by these astrocytes that could modulate NSPC differentiation, we performed gene expression profiling analysis using Affymetrix rat genome arrays. Our results demonstrated that these astrocytes had distinct gene expression profiles. We further tested the functional effects of candidate factors that were differentially expressed in neurogenesis-promoting and -inhibiting astrocytes using in vitro NSPC differentiation assays. Our results indicated that two interleukins, IL-1/3 and IL-6, and a combination of factors that included these two interleukins could promote NSPC neuronal differentiation, whereas insulin-like growth factor binding protein 6 (IGFBP6) and decorin inhibited neuronal differentiation of adult NSPCs. Our results have provided further evidence to support the ongoing hypothesis that, in adult mammalian brains, astrocytes play critical roles in modulating NSPC differentiation. The finding that cytokines and chemokines expressed by astrocytes could promote NSPC neuronal differentiation may help us to understand how injuries induce neurogenesis in adult brains.

UR - http://www.scopus.com/inward/record.url?scp=33746255997&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33746255997&partnerID=8YFLogxK

U2 - 10.1089/scd.2006.15.407

DO - 10.1089/scd.2006.15.407

M3 - Article

C2 - 16846377

AN - SCOPUS:33746255997

VL - 15

SP - 407

EP - 421

JO - Stem Cells and Development

JF - Stem Cells and Development

SN - 1547-3287

IS - 3

ER -