Regionally-specified second trimester fetal neural stem cells reveals differential neurogenic programming

PLoS One. 2014 Sep 2;9(9):e105985. doi: 10.1371/journal.pone.0105985. eCollection 2014.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers / metabolism
  • Brain / cytology
  • Brain / embryology
  • Cell Differentiation
  • Cell Proliferation
  • Female
  • Fetal Stem Cells / cytology*
  • Humans
  • Immunohistochemistry
  • Neural Stem Cells / cytology*
  • Neural Stem Cells / metabolism
  • Neurogenesis*
  • Neurons / cytology
  • Neurons / metabolism
  • Oligonucleotide Array Sequence Analysis
  • Organ Specificity*
  • Pregnancy
  • Pregnancy Trimester, Second / physiology*
  • Spheroids, Cellular / cytology
  • Spheroids, Cellular / metabolism
  • Stem Cell Transplantation

Substances

  • Biomarkers

Grants and funding

This work was funded by a grant from the Clinician Scientist Unit, NUS to J.K.Y. Chan, and Competitive Research Program (CRP) funds from National Research Foundation, Singapore to E.L.K. Goh. J.K.Y. Chan and M.A. Choolani received salary support from Clinician Scientist Award, National Medical Research Council, Singapore (NMRC/CSA/009/2009 and NMRC/CSA/043/2012). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.