||Sayako Katada, Molecular characterization of aging choroid plexus that regulates neural stem cell’s behavior and brain functions, 第43回日本分子生物学会年会, 2020.12, The choroid plexus (ChP), located in each brain ventricles, produces cerebrospinal fluid (CSF) and secretes various cytokines and growth factors into the CSF. Although several studies have reported that CSF serves as a niche for NSCs regulating neurogenesis, little is known about the aging changes. Since the ChP is sensitive to peripheral body signals, and gates immune cells to brain, disruption of ChP function and CSF composition are common to neurological disorders, such as multiple sclerosis, ischemia and Alzheimer`s disease. Despite these essential roles, remarkably little is known for the molecular mechanisms governing these functions of the ChP. Herein, we performed mRNA-seq analyses together with small RNA-seq of the ChP in the lateral ventricle using young (3-4 months) and aged (21-24 months) mice, and identified several sets of differentially expressed mRNA/miRNA. Global analysis of expressed genes in the lateral ventricle ChP cells revealed that the most overrepresented gene ontology terms in the aged mice are related to the inflammatory response. Indeed, single cell RNA-seq analysis clearly revealed that some population of aged ChP cells express higher level of chemokines such as Cxcl12/13 that linked to immune cell recruitment. In addition to the inflammatory response, several sets of ChP-expressed miRNA seemed to directly regulate NSCs proliferation. Taken together, our findings shed new light on the function of the ChP, and will facilitate future studies to design active and healthy brain barrier system..
||Sayako Katada, ＃Yusuke Sakaki, Rie Yamashita, Takuya Imamura and Kinichi Nakashima, Impact of structure and property changes of aging choroid plexus on neural stem cell regulation and brain functions, Keystone Symposia, 2020.02, Although neural stem cells (NSCs) produce new neurons even in adulthood, neurogenesis decreases in the brain with aging, and little is known about the underlying mechanisms. Several studies have reported that cerebrospinal fluid (CSF), which is primarily produced by the choroid plexus (ChP) in ventricles, serves as a niche for NSCs. ChP is a highly vascularized epithelial tissue constituting blood-CSF barrier and secretes various cytokines and growth factors into the CSF. We have recently performed mRNA-seq analyses together with small RNA-seq of the ChP in the lateral ventricle (LVChP) using young (3-4 months) and aged (21-24 months) mice, and identified several sets of differentially expressed mRNA/miRNA. Global analysis of expressed genes in the LVChP revealed that the most overrepresented gene ontology terms in the aged mice are related to the inflammatory response. Indeed, single cell RNA-seq analysis clearly revealed that some population of LVChP cells express higher level of chemokines such as Cxcl12/13 in aged mice. In addition to the inflammatory response, several sets of LVChP-expressed miRNA seemed to directly regulate NSCs proliferation. Taken together, our findings strongly suggest the potential of ChP in neural stem cells regulation and brain functions..
||Sayako Katada, Mizuki Honda, Jun Takouda, Katsuhide Igarashi, and Kinichi Nakashima, Developmental stage-dependent change of SMAD target genes defines the direction of neural stem cell differentiation induced by bone morphogenetic proteins, EMBO Conference Gene regulatory mechanisms in neural fate decision, 2017.09.
||Sayako Katada, Implication of structure and functional changes of aging choroid plexus in neural stem cells regulation and brain functions, 2017.01.
||Choroid Plexus as the key regulator for development, maturation, and aging of the central nervous system.
||堅田 明子, Impact of oxygen levels on fate switching of neural stem cell during corticogenesis, Neuro 2013, 2013.06, Oxygen (O2) is a substrate for energy production and deeply involved in the regulations of cellular metabolism. Although standard cell culture systems are exposed to the environmental O2 level of 21% (normoxia), actual O2 concentration in both developing and adult brains is 1-8% (hypoxia). Accumulating studies have revealed that O2 and its signal transduction pathways control cell proliferation, differentiation, and morphogenesis during the development of various tissues. The mammalian brain cortex comprises deep- and upper-layer neurons (layer V-VI and II-IV, respectively) and glial cells including astrocytes. All these cells are sequentially generated from common multipotent neural stem cells (NSCs) in this order during development. Therefore, NSCs at midgestation produce neither upper-layer neuron nor astrocyte, but mainly differentiate into deep-layer neurons. In addition, it is generally known that this NSC’s property change can be recapitulated in the embryonic stem (ES) cell culture systems. Recently, we have shown that the acquisition of astrogenic potential by NSCs is delayed in standard in vitro culture compared to those in vivo, while, in vitro culture under hypoxic condition can restore this impairment. Herein, we further analyze the impact of O2 levels during corticogenesis, i.e. deep- and upper-layer neuron production of NSCs. Mouse ES cells were cultured and induced to neural differentiation under normoxic or hypoxic condition, and the differentiation was evaluated by quantitative PCR and immunocytochemistry. We found that the expression of upper-layer specific neuronal genes in hypoxia culture appeared earlier than that in normoxia. Thus, it is conceivable that O2 levels contribute to appropriate scheduling of not only neuron-glia fate switching but also neuronal subtype specification throughout development..