title: Regionally-specified second trimester fetal neural stem cells reveals differential neurogenic programming.
abstract: Neural stem/progenitor cells (NSC) have the potential for treatment of a wide range of neurological diseases such as Parkinson Disease and multiple sclerosis. Currently, NSC have been isolated only from hippocampus and subventricular zone (SVZ) of the adult brain. It is not known whether NSC can be found in all parts of the developing mid-trimester central nervous system (CNS) when the brain undergoes massive transformation and growth. Multipotent NSC from the mid-trimester cerebra, thalamus, SVZ, hippocampus, thalamus, cerebellum, brain stem and spinal cord can be derived and propagated as clonal neurospheres with increasing frequencies with increasing gestations. These NSC can undergo multi-lineage differentiation both in vitro and in vivo, and engraft in a developmental murine model. Regionally-derived NSC are phenotypically distinct, with hippocampal NSC having a significantly higher neurogenic potential (53.6%) over other sources (range of 0%-27.5%, p<0.004). Whole genome expression analysis showed differential gene expression between these regionally-derived NSC, which involved the Notch, epidermal growth factor as well as interleukin pathways. We have shown the presence of phenotypically-distinct regionally-derived NSC from the mid-trimester CNS, which may reflect the ontological differences occurring within the CNS. Aside from informing on the role of such cells during fetal growth, they may be useful for different cellular therapy applications.
authors.affiliation: Department of Reproductive Medicine, KK Women's and Children's Hospital, Singapore, Singapore; Experimental Fetal Medicine Group, Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University Health System, Singapore, Singapore.
authors.forename: Yiping
authors.initials: Y
authors.lastname: Fan
authors.affiliation: Neuroscience and Behavioral Disorder Program, Duke-NUS Graduate Medical School, Singapore, Singapore.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Marcy
authors.affiliation: Richard M. Lucas Center for Imaging, Radiology Department, Stanford University, Stanford, California, United States of America.
authors.forename: Eddy S M
authors.initials: ES
authors.lastname: Lee
authors.affiliation: Cancer and Stem Cell Biology Program, Duke-NUS Graduate Medical School, Singapore, Singapore.
authors.forename: Steve
authors.initials: S
authors.lastname: Rozen
authors.affiliation: Experimental Fetal Medicine Group, Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University Health System, Singapore, Singapore.
authors.forename: Citra N Z
authors.initials: CN
authors.lastname: Mattar
authors.affiliation: Gene Transfer Technology Group, Institute for Women's Health, University College London, London, United Kingdom; Faculty of Health Sciences, University of the Witswatersrand, Johannesburg, South Africa.
authors.forename: Simon N
authors.initials: SN
authors.lastname: Waddington
authors.affiliation: Neuroscience and Behavioral Disorder Program, Duke-NUS Graduate Medical School, Singapore, Singapore.
authors.forename: Eyleen L K
authors.initials: EL
authors.lastname: Goh
authors.affiliation: Experimental Fetal Medicine Group, Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University Health System, Singapore, Singapore.
authors.forename: Mahesh
authors.initials: M
authors.lastname: Choolani
authors.affiliation: Department of Reproductive Medicine, KK Women's and Children's Hospital, Singapore, Singapore; Experimental Fetal Medicine Group, Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University Health System, Singapore, Singapore; Cancer and Stem Cell Biology Program, Duke-NUS Graduate Medical School, Singapore, Singapore.
authors.forename: Jerry K Y
authors.initials: JK
authors.lastname: Chan
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000166:cytology / Q000196:embryology; D002454:Cell Differentiation; D049109:Cell Proliferation; D005260:Female; D053686:Fetal Stem Cells / Q000166:cytology*; D006801:Humans; D007150:Immunohistochemistry; D058953:Neural Stem Cells / Q000166:cytology* / Q000378:metabolism; D055495:Neurogenesis; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D009928:Organ Specificity; D011247:Pregnancy; D011262:Pregnancy Trimester, Second / Q000502:physiology*; D018874:Spheroids, Cellular / Q000166:cytology / Q000378:metabolism; D033581:Stem Cell Transplantation
chemical_list: D015415:Biomarkers