You are here

Characterization of neural cells derived from reelin-deficient schizophrenic patient iPS cells

Download pdf | Full Screen View

Date Issued:
2018
Abstract/Description:
Reelin is a large, extracellular glycoprotein that binds to several membrane receptors on neural stem cells (HNSCs), neural progenitor cells (NPCs), and neuroblasts of mammals to direct their migration. Previously, our lab established the presence of Reelin increased migration of wild-type fetal-derived HNSC's, both in vitro and in vivo. In addition, we demonstrated that Reelin protein treatment also increases the formation of radial glia via Notch-1 signaling, in vitro. Radial glia are precursors to NPCs, as well as a scaffold for neuroblast migration during cortical lamination. Reelin has long been associated with Schizophrenia (SZ). Because post-mortem brains are limited to describing the end-point of the disease, heterozygous haplodeficient Reelin knock-out (Reeler) mice are used to model developmental aspects of SZ in vivo. However, SZ is a complex, polyfactoral disease with a myriad of dysfunctional pathways that may have unforeseen effects on Reelin signaling. K. Brennand et al. (2014) reported low Reelin mRNA expression and cellular characteristics mirroring the Reeler mouse in induced pluripotent stem (iPS) cell-derived NPCs and neurons from living SZ patients. Building upon this and our work with stem cells, here we consider Reelin's effects on migration of Reelin-deficient iPS cell-derived NPCs. Reelin treatment of consists of secreted Reelin from transfected human embryonic kidney 293 cells (HEK 293) with the pCRL RELN gene-containing plasmid created by G. D'Arcangelo (1997) and given to us by T. Curran. Using the metric of cellular migration, this is the first time it have been shown that SZ iNPCs are capable of receiving and reacting to extracellular Reelin. Due to our validation of this model, further work using iPS cell-derived neural cells can confidently be used for future disease modeling and drug discovery of Reelin-deficient SZ.
Title: Characterization of neural cells derived from reelin-deficient schizophrenic patient iPS cells.
0 views
0 downloads
Name(s): Roberts, Nicole, Author
Sugaya, Kiminobu, Committee Chair
Ebert, Steven, Committee Member
Masternak, Michal, Committee Member
University of Central Florida, Degree Grantor
Type of Resource: text
Date Issued: 2018
Publisher: University of Central Florida
Language(s): English
Abstract/Description: Reelin is a large, extracellular glycoprotein that binds to several membrane receptors on neural stem cells (HNSCs), neural progenitor cells (NPCs), and neuroblasts of mammals to direct their migration. Previously, our lab established the presence of Reelin increased migration of wild-type fetal-derived HNSC's, both in vitro and in vivo. In addition, we demonstrated that Reelin protein treatment also increases the formation of radial glia via Notch-1 signaling, in vitro. Radial glia are precursors to NPCs, as well as a scaffold for neuroblast migration during cortical lamination. Reelin has long been associated with Schizophrenia (SZ). Because post-mortem brains are limited to describing the end-point of the disease, heterozygous haplodeficient Reelin knock-out (Reeler) mice are used to model developmental aspects of SZ in vivo. However, SZ is a complex, polyfactoral disease with a myriad of dysfunctional pathways that may have unforeseen effects on Reelin signaling. K. Brennand et al. (2014) reported low Reelin mRNA expression and cellular characteristics mirroring the Reeler mouse in induced pluripotent stem (iPS) cell-derived NPCs and neurons from living SZ patients. Building upon this and our work with stem cells, here we consider Reelin's effects on migration of Reelin-deficient iPS cell-derived NPCs. Reelin treatment of consists of secreted Reelin from transfected human embryonic kidney 293 cells (HEK 293) with the pCRL RELN gene-containing plasmid created by G. D'Arcangelo (1997) and given to us by T. Curran. Using the metric of cellular migration, this is the first time it have been shown that SZ iNPCs are capable of receiving and reacting to extracellular Reelin. Due to our validation of this model, further work using iPS cell-derived neural cells can confidently be used for future disease modeling and drug discovery of Reelin-deficient SZ.
Identifier: CFE0007361 (IID), ucf:52091 (fedora)
Note(s): 2018-12-01
M.S.
Medicine, Biomedical Sciences
Masters
This record was generated from author submitted information.
Subject(s): reelin -- reln -- schizophrenia -- iPS cells -- HNSC -- NPCs -- neurons -- migration
Persistent Link to This Record: http://purl.flvc.org/ucf/fd/CFE0007361
Restrictions on Access: public 2018-12-15
Host Institution: UCF

In Collections