PINK1 expression increases during brain development and stem cell differentiation, and affects the development of GFAP-positive astrocytes

Insup Choi, Dong Joo Choi, Haijie Yang, Joo Hong Woo, Mi Yoon Chang, Joo Yeon Kim, Woong Sun, Sang Myun Park, Ilo Jou, Sang Hoon Lee, Eun Hye Joe

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Background: Mutation of PTEN-induced putative kinase 1 (PINK1) causes autosomal recessive early-onset Parkinson's disease (PD). Despite of its ubiquitous expression in brain, its roles in non-neuronal cells such as neural stem cells (NSCs) and astrocytes were poorly unknown. Results: We show that PINK1 expression increases from embryonic day 12 to postnatal day 1 in mice, which represents the main period of brain development. PINK1 expression also increases during neural stem cell (NSC) differentiation. Interestingly, expression of GFAP (a marker of astrocytes) was lower in PINK1 knockout (KO) mouse brain lysates compared to wild-type (WT) lysates at postnatal days 1-8, whereas there was little difference in the expression of markers for other brain cell types (e.g., neurons and oligodendrocytes). Further experiments showed that PINK1-KO NSCs were defective in their differentiation to astrocytes, producing fewer GFAP-positive cells compared to WT NSCs. However, the KO and WT NSCs did not differ in their self-renewal capabilities or ability to differentiate to neurons and oligodendrocytes. Interestingly, during differentiation of KO NSCs there were no defects in mitochondrial function, and there were not changes in signaling molecules such as SMAD1/5/8, STAT3, and HES1 involved in differentiation of NSCs into astrocytes. In brain sections, GFAP-positive astrocytes were more sparsely distributed in the corpus callosum and substantia nigra of KO animals compared with WT. Conclusion: Our study suggests that PINK1 deficiency causes defects in GFAP-positive astrogliogenesis during brain development and NSC differentiation, which may be a factor to increase risk for PD.

Original languageEnglish
Article number5
JournalMolecular Brain
Volume9
Issue number1
DOIs
Publication statusPublished - 2016 Jan 8

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Neural Stem Cells
Astrocytes
Brain Stem
Cell Differentiation
Stem Cells
Brain
Oligodendroglia
Neurons
PTEN-induced putative kinase
Corpus Callosum
Parkinsonian Disorders
Substantia Nigra
Knockout Mice
Parkinson Disease
Mutation

Keywords

  • Astrocyte
  • Neural stem cell
  • Parkinson's disease
  • PINK1

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Molecular Biology

Cite this

PINK1 expression increases during brain development and stem cell differentiation, and affects the development of GFAP-positive astrocytes. / Choi, Insup; Choi, Dong Joo; Yang, Haijie; Woo, Joo Hong; Chang, Mi Yoon; Kim, Joo Yeon; Sun, Woong; Park, Sang Myun; Jou, Ilo; Lee, Sang Hoon; Joe, Eun Hye.

In: Molecular Brain, Vol. 9, No. 1, 5, 08.01.2016.

Research output: Contribution to journalArticle

Choi, Insup ; Choi, Dong Joo ; Yang, Haijie ; Woo, Joo Hong ; Chang, Mi Yoon ; Kim, Joo Yeon ; Sun, Woong ; Park, Sang Myun ; Jou, Ilo ; Lee, Sang Hoon ; Joe, Eun Hye. / PINK1 expression increases during brain development and stem cell differentiation, and affects the development of GFAP-positive astrocytes. In: Molecular Brain. 2016 ; Vol. 9, No. 1.
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abstract = "Background: Mutation of PTEN-induced putative kinase 1 (PINK1) causes autosomal recessive early-onset Parkinson's disease (PD). Despite of its ubiquitous expression in brain, its roles in non-neuronal cells such as neural stem cells (NSCs) and astrocytes were poorly unknown. Results: We show that PINK1 expression increases from embryonic day 12 to postnatal day 1 in mice, which represents the main period of brain development. PINK1 expression also increases during neural stem cell (NSC) differentiation. Interestingly, expression of GFAP (a marker of astrocytes) was lower in PINK1 knockout (KO) mouse brain lysates compared to wild-type (WT) lysates at postnatal days 1-8, whereas there was little difference in the expression of markers for other brain cell types (e.g., neurons and oligodendrocytes). Further experiments showed that PINK1-KO NSCs were defective in their differentiation to astrocytes, producing fewer GFAP-positive cells compared to WT NSCs. However, the KO and WT NSCs did not differ in their self-renewal capabilities or ability to differentiate to neurons and oligodendrocytes. Interestingly, during differentiation of KO NSCs there were no defects in mitochondrial function, and there were not changes in signaling molecules such as SMAD1/5/8, STAT3, and HES1 involved in differentiation of NSCs into astrocytes. In brain sections, GFAP-positive astrocytes were more sparsely distributed in the corpus callosum and substantia nigra of KO animals compared with WT. Conclusion: Our study suggests that PINK1 deficiency causes defects in GFAP-positive astrogliogenesis during brain development and NSC differentiation, which may be a factor to increase risk for PD.",
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AU - Choi, Insup

AU - Choi, Dong Joo

AU - Yang, Haijie

AU - Woo, Joo Hong

AU - Chang, Mi Yoon

AU - Kim, Joo Yeon

AU - Sun, Woong

AU - Park, Sang Myun

AU - Jou, Ilo

AU - Lee, Sang Hoon

AU - Joe, Eun Hye

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AB - Background: Mutation of PTEN-induced putative kinase 1 (PINK1) causes autosomal recessive early-onset Parkinson's disease (PD). Despite of its ubiquitous expression in brain, its roles in non-neuronal cells such as neural stem cells (NSCs) and astrocytes were poorly unknown. Results: We show that PINK1 expression increases from embryonic day 12 to postnatal day 1 in mice, which represents the main period of brain development. PINK1 expression also increases during neural stem cell (NSC) differentiation. Interestingly, expression of GFAP (a marker of astrocytes) was lower in PINK1 knockout (KO) mouse brain lysates compared to wild-type (WT) lysates at postnatal days 1-8, whereas there was little difference in the expression of markers for other brain cell types (e.g., neurons and oligodendrocytes). Further experiments showed that PINK1-KO NSCs were defective in their differentiation to astrocytes, producing fewer GFAP-positive cells compared to WT NSCs. However, the KO and WT NSCs did not differ in their self-renewal capabilities or ability to differentiate to neurons and oligodendrocytes. Interestingly, during differentiation of KO NSCs there were no defects in mitochondrial function, and there were not changes in signaling molecules such as SMAD1/5/8, STAT3, and HES1 involved in differentiation of NSCs into astrocytes. In brain sections, GFAP-positive astrocytes were more sparsely distributed in the corpus callosum and substantia nigra of KO animals compared with WT. Conclusion: Our study suggests that PINK1 deficiency causes defects in GFAP-positive astrogliogenesis during brain development and NSC differentiation, which may be a factor to increase risk for PD.

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