Guo, Weixiang

Ladewig, Julia

Liu, Yan

Meyer, Jason S.

Weick, Jason P.

PubMed

Jason P. Weick

Jason S. Meyer

Julia Ladewig

Weixiang Guo

Yan Liu

Directory of Open Access Journals

Stem Cells International

Modeling CNS Development and Disease

IUPUIScholarWorks

Crossref

EditorialModeling CNS Development and DiseaseJason P. Weick,1 Jason S. Meyer,2 Julia Ladewig,3 Weixiang Guo,4 and Yan Liu51Department of Neurosciences, University of New Mexico-HSC, Albuquerque, NM 87131-0001, USA2Department of Biology/Stark Neurosciences Research Institute, Indiana University-Purdue University Indianapolis,Indianapolis, IN 46202, USA3Institute of Reconstructive Neurobiology, University of Bonn, 53127 Bonn, Germany4Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China5Institute for Stem Cell and Neural Regeneration, School of Pharmacy, Nanjing Medical University, Nanjing, ChinaCorrespondence should be addressed to Jason P. Weick; jpweick@salud.unm.eduReceived 14 July 2016; Accepted 14 July 2016Copyright © 2016 Jason P. Weick et al. This is an open access article distributed under the Creative Commons Attribution License,which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.The ultimate goals for stem cell researchers are uncoveringthe fundamental mechanisms of cellular biology as well asdeveloping treatments for disease and/or injury. The centralnervous system (CNS) presents an unparalleled challengefor these studies due to the diversity of cell types andtheir interrelated functions in health and disease. Further-more, the endpoints for determining phenotypic maturationare complicated by the fact that cells, especially neurons,express a plethora of receptors and ion channels that controlexcitability and plasticity which vary greatly between CNSregions. For this reason, extensive effort has been placed ondeveloping methods to differentiate appropriate populationsof cells that reside within the CNS (e.g., neuronal subtypes,astrocytes, and oligodendrocytes). These studies typicallyemploy phenotypic validation by the use of expression anal-ysis for various protein markers of regionalized populations,with a burgeoning effort to verify functional outcomes.Muchof this work has been informed by basic developmentalstudies that have identified cell-intrinsic and cell-extrinsicsignaling mechanisms, as well as transcriptional programsinvolved with cell fate specification.While early work focused on the use of mesenchymalstem cells, embryonic carcinoma cells, and fetal stem cells,more recent efforts have focused on the areas of humanembryonic stem cells (hESCs) and induced pluripotent stemcells (iPSCs). These sources typically require slightly differ-ent methods to direct differentiation to various CNS fates,although many mechanisms appear to converge on commonsignaling pathways. Many recent studies have even success-fully uncovered cell-type specific phenotypes that are appro-priate for various human diseases. However, despite theseadvances, limitations still hamper the application of humanstem cells for CNS development/disease studies. First, mostdifferentiation protocols lead to a heterogeneity of cells interms of both their “regional”markers and theirmaturationalstates. Furthermore, the number and diversity of availablefate-specific biomarkers remain insufficient to unambigu-ously identify regional and transmitter phenotypes.In this special issue, we highlight both the advancementsand challenges of directed differentiation of various neuronaland glial cells from pluripotent stem cells. We hope thiscollection of works will provide readers with a resourceto understand directed differentiation, functional matura-tion, and transplantation-induced changes to host environ-ments.The article by P. Prajumwongs et al. reviews the currentstate of knowledge regarding neural induction of humanpluripotent stem cells, detailing the signaling pathways andtiming of critical events such as neuroepithelial differentia-tion. Emphasis is placed on the comparison between in vitroand in vivo development and the utility of hESCs to modelhuman-specific signaling processes. The article concludeswith a series of brief descriptions about various develop-mental and neurodegenerative diseases and how iPSCs havebeen used to model their underlying molecular and cellularpathologies.Hindawi Publishing CorporationStem Cells InternationalVolume 2016, Article ID 3241057, 2 pageshttp://dx.doi.org/10.1155/2016/32410572 Stem Cells InternationalThe review article from A. Zirra et al. gives a detailedoverview of the development of the neural tube and howthese in vivo principles provided the basis for in vitroneural induction strategies of human pluripotent stem cells(hPSCs). The article highlights the basic stages of neuraldevelopment including neural induction, neurulation, andneural patterning. Here they focus on signaling pathways,morphogenes, and patterning factors described to be crucialfor the development of distinct brain regions. The authorsthen discuss how knowledge from in vivo brain developmenthas been translated by many groups to direct the differentia-tion of hPSCs to clinically relevant region-specific neuronsin vitro. Finally, they give an outlook of how human braindevelopment data can be utilized for improving directeddifferentiation protocols and validating the thereof derivedregion-specific subpopulations of human neurons.The article by F. Cavaliere et al. reviews the use of organ-otypic hippocampal slice cultures as a model for understand-ing neurogenesis under normal and pathological conditions.They first present a historical summary of the development ofslice cultures fromneonatal, andmore recently adult animals,for the study of neurogenesis from both SVZ and DGZ.The article also describes results from pathological studiesof slice cultures in the context of ischemia, Parkinson’s, andAlzhemier’s disease, as well as regeneration of neurons in thespinal cord. The authors suggest that the maintenance of the3D architecture and cellular composition of these culturesmake them unique among in vitro models for these types ofstudies.The primary research article from T. H. Shin et al. testedthe effects of mesenchymal stem cells on polyamine levelsin both in vitro and in vivo models of ischemic stroke.Polyamines are low molecular weight compounds secretedin high concentrations from the brain and are importantindicators of metabolic function, especially in response toinjury or disease. The authors found that middle cerebralartery occlusion (MCAo) in vivo and oxygen-glucose depri-vation (OGD) of a neural cell line in vitro significantly altereda plurality of polyamine levels. Importantly, the authorsfound that disruptions of polyamine levels by MCAo- andOGD-induced ischemic conditions could be restored to near-normal levels after introduction of human bone marrow-derived mesenchymal stem cells.Finally, the review article from J. P. Weick highlightsthe efforts by many groups to understand the functionalphenotypes of pluripotent stem cell-derived neurons as wellas directly converted/induced neurons (iNs). This articlefocuses on the assessment of developmental maturation offorebrain neurons via analysis of forebrain glutamatergic andGABAergic currents, comparing these in vitro findings toin vivo data from rodent models. The author then discussesrecent results modeling various neurological disorders usingiPSC-derived neurons and iNs. He concludes by criticallyreflecting on the use of these two cell types for developmentaland disease studies and provides suggestions on how tooptimally determine and report neuronal function.Together, the articles in this special issue highlight recentadvances in our understanding of the directed differentiationand functional properties of stem cells and describe severalnew approaches to model and develop novel therapies forneurological disease and injury.Jason P. WeickJason S. MeyerJulia LadewigWeixiang GuoYan Liu

https://creativecommons.org/licenses/by/4.0/

Modeling CNS Development and Disease

Abstract

Similar works

Full text

Available Versions

Directory of Open Access Journals

IUPUIScholarWorks

Crossref

IUPUIScholarWorks