Cheol Woo Lee

The Molecular Profiles of Neural Stem Cell Niche in the Adult Subventricular Zone

Neural stem cells (NSCs) reside in a unique microenvironment called the neurogenic niche and generate functional new neurons. The neurogenic niche contains several distinct types of cells and interacts with the NSCs in the subventricular zone (SVZ) of the lateral ventricle. While several molecules produced by the niche cells have been identified to regulate adult neurogenesis, a systematic profiling of autocrine/paracrine signaling molecules in the neurogenic regions involved in maintenance, self-renewal, proliferation, and differentiation of NSCs has not been done. We took advantage of the genetic inducible fate mapping system (GIFM) and transgenic mice to isolate the SVZ niche cells including NSCs, transit-amplifying progenitors (TAPs), astrocytes, ependymal cells, and vascular endothelial cells. From the isolated cells and microdissected choroid plexus, we obtained the secretory molecule expression profiling (SMEP) of each cell type using the Signal Sequence Trap method. We identified a total of 151 genes encoding secretory or membrane proteins. In addition, we obtained the potential SMEP of NSCs using cDNA microarray technology. Through the combination of multiple screening approaches, we identified a number of candidate genes with a potential relevance for regulating the NSC behaviors, which provide new insight into the nature of neurogenic niche signals.

Gli3 Repressor Controls Cell Fates and Cell Adhesion for Proper Establishment of Neurogenic Niche

Neural stem cells (NSCs) in the subventricular zone (SVZ) rely on environmental signals provided by the neurogenic niche for their proper function. However, little is known about the initial steps of niche establishment, as embryonic radial glia transition to postnatal NSCs. Here, we identify Gli3 repressor (Gli3R), a component of the Sonic hedgehog (Shh) pathway, as a critical factor controlling both cell-type specification and structural organization of the developing SVZ. We demonstrate that Gli3R expressed in radial glia temporally regulates gp130/STAT3 signaling at the transcriptional level to suppress glial characteristics in differentiating ependymal cells. In addition, Gli3R maintains the proper level of Numb in ependymal cells to allow localization of cell adhesion molecules such as vascular cell adhesion molecule (VCAM) and E-cadherin. Thus, our findings reveal a role for Gli3R as a mediator of niche establishment and provide insights into the conditions required for proper SVZ neurogenic niche formation.

Neurotrophic Factor‐α1: A Key Wnt‐β‐Catenin Dependent Anti‐Proliferation Factor and ERK‐Sox9 Activated Inducer of Embryonic Neural Stem Cell Differentiation to Astrocytes in Neurodevelopment

Embryonic neurodevelopment involves inhibition of proliferation of multipotent neural stem cells (NSCs) followed by differentiation into neurons, astrocytes and oligodendrocytes to form the brain. We have identified a new neurotrophic factor, NF‐α1, which inhibits proliferation and promotes differentiation of NSC/progenitors derived from E13.5 mouse cortex. Inhibition of proliferation of these cells was mediated through negatively regulating the Wnt pathway and decreasing β‐catenin. NF‐α1 induced differentiation of NSCs to astrocytes by enhancing Glial Fibrillary Acidic Protein (GFAP) expression through activating the ERK1/2‐Sox9 signaling pathway. Cultured E13.5 cortical stem cells from NF‐α1‐knockout mice showed decreased astrocyte numbers compared to wild‐type mice, which was rescued by treatment with NF‐α1. In vivo, immunocytochemistry of brain sections and Western blot analysis of neocortex of mice showed a gradual increase of NF‐α1 expression from E14.5 to P1 and a surge of GFAP expression at P1, the time of increase in astrogenesis. Importantly, NF‐α1‐Knockout mice showed ∼49% fewer GFAP positive astrocytes in the neocortex compared to WT mice at P1. Thus, NF‐α1 is critical for regulating antiproliferation and cell fate determination, through differentiating embryonic stem cells to GFAP‐positive astrocytes for normal neurodevelopment. Stem Cells 2017;35:557–571

Preliminary Study on Applying Discrete Ordinates Code Supporting Unstructured Tetrahedral Mesh to the 40-Degree Toroidal Segment ITER Model

Abstract The discrete ordinates code under development by KAERI uses an unstructured tetrahedral mesh, and can thus be applied to solve the radiation transport in a complicated geometry. In addition, the geometry modeling process has become much easier because computational tetrahedral meshes are generated based on the CAD file by Gmsh. This program has been enhancing its performance and adding functions for each application. In previous research, it was applied in a neutronics analysis for the Korea Helium Cooled Ceramic Reflector (HCCR) TBM. The total neutron fluxes were compared with the results from MCNPX and showed good agreement. In this paper, we applied our program to a simplified ITER model which is a 40-degree toroidal segment. The zone averaged total fluxes were compared with those of MCNPX, and total neutron flux distribution was visualized in a three-dimensional system domain.

Analysis of the Neutron Thermalization in an Accelerator Room

The estimation of the thermalized neutrons in the accelerator room is one of the important shielding problems in the facility design and the evaluation of the worker’s exposure. In an accelerator room, high energy neutrons produced by an accelerator lose their energy by the multiple collisions with the wall, floor, or ceiling and are reflected from concrete wall’s surfaces as thermal neutrons. The simple empirical formula, φth = CQ / S, is widely used as an estimation for the neutron thermalization. Where φth is a thermal neutron flux in the room, Q is the intensity of the source neutron, S is the inner surface area for an accelerator room and C is the coefficient as a fitting parameter. In this study, various factors including S were examined to evaluate the value of C based on the MCNP simulation. The dependence on room size, room shape, energy of the source neutron and distance from the source were analyzed by using MCNPX code. As a result, the modified estimation, φth = Σg CgQg / S, and Cg dependant on energy group of the source neutron were proposed. The proposed estimation was also compared with the results from other estimation method and MCNPX calculations.

Evaluation of Skyshine Dose for the Proton Accelerator Facility of the Proton Engineering Frontier Project in Korea

Abstract Evaluation of the skyshine dose for the proton linac facility of the Proton Engineering Frontier Project in Korea was performed in this study. To predict the skyshine dose level outside of the facility, a Monte Carlo method (MCNPX code), analytical method using an estimation formula, and SKYSHINE-KSU codes using an integral line-beam method were considered in the evaluations. The neutron spectrum at the outer surface of the roof of the facility was considered as the radiation source term. The results from each method were in good agreement for the distance from 200 to 1000 m. The neutron dose of 1.65 × 10-4 μSv/h is expected at the fence of the facility, which is 400 m from the accelerator room.