a-neurosphere-assay-to-evaluate-endogenous-neural-stem-cell

A Neurosphere Assay to Evaluate Endogenous Neural Stem Cell Activation in a Mouse Model of Minimal Spinal Cord Injury

Neural stem cells (NSCs) in the adult mammalian spinal cord are a relatively mitotically quiescent population of periventricular cells that can be studied ...

University of Toronto

Adult forebrain definitive neural stem cells (NSCs) comprise a subpopulation of GFAP-expressing subependymal cells that arise from embryonic fibroblast growth factor (FGF)-dependent NSCs that are first isolated from the developing brain at E8.5. Embryonic FGF-dependent NSCs are derived from leukemia inhibitory factor (LIF)-responsive, Oct4-expressing primitive NSCs (pNSCs) that are first isolated at E5.5. We report the presence of a rare population of pNCSs in the periventricular region of the adult forebrain. Adult-derived pNSCs (AdpNSCs) are GFAP(-), LIF-responsive stem cells that display pNSC properties, including Oct4 expression and the ability to integrate into the inner cell mass of blastocysts. AdpNSCs generate self-renewing, multipotent colonies that give rise to definitive GFAP(+) NSCs in vitro and repopulate the subependyma after the ablation of GFAP(+) NSCs in vivo. These data support the hypothesis that a rare population of pNSCs is present in the adult brain and is upstream of the GFAP(+) NSCs. 

Primitive neural stem cells in the adult mammalian brain give rise to GFAP-expressing neural stem cells.

The adult mammalian forebrain comprises two distinct populations of neural stem cells (NSCs): rare, Oct4 positive, primitive NSCs (pNSCs) and definitive NSC (dNSC) which are more abundant and express GFAP. The pNSCs are upstream of the dNSCs in the neural stem cell lineage. Herein we show that pNSC and dNSC populations can also be isolated from the developing and adult spinal cord. Spinal cord derived pNSCs are similarly rare, Oct4 expressing cells that are responsive to leukemia inhibitory factor and dNSCs are 4-5X more abundant and express GFAP. We demonstrate that myelin basic protein (MBP) is inhibitory to both pNSC and dNSC derived colony formation. Similar to what is seen in the adult forebrain following injury, spinal cord injury results in a significant increase in the size of the dNSC and pNSC pools. Hence, both primitive and definitive neural stem cells can be isolated from along the embryonic and adult neuraxis in vivo and their behavior is regulated by MBP and injury. Stem Cells 2017;35:485-496.

Myelin Basic Protein Regulates Primitive and Definitive Neural Stem Cell Proliferation from the Adult Spinal Cord.

Stem cells in the adult CNS revealed: examining their regulation by myelin basic protein.

Neural stem cells (NSCs) are a multipotent, self-renewing source of undifferentiated cells in the periventricular region of the mammalian central nervous system (CNS). Since their original discovery 25 years ago, much has been learned about their development, persistence, localization, properties and potential. Herein we discuss the current state of knowledge pertaining to neural stem cells with a focus on the lineage relationship between two NSC populations along the neuraxis and their regionally distinct niches in the CNS.

Wenjun Xu

Department of Surgery

University of Toronto

A Neurosphere Assay to Evaluate Endogenous Neural Stem Cell Activation in a Mouse Model of Minimal Spinal Cord Injury

Wenjun Xu

.css-o250i3{font-size:18px;font-family:Open Sans,sans-serif;line-height:21.6px;}Department of Surgery

University of Toronto

A Neurosphere Assay to Evaluate Endogenous Neural Stem Cell Activation in a Mouse Model of Minimal Spinal Cord Injury

Department of Surgery