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

Stem Cells. 2017 Feb;35(2):485-496. doi: 10.1002/stem.2488. Epub 2016 Sep 23.

Abstract

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.

Keywords: Adult neural stem cells; GFAP+ neural stem cells; Myelin basic protein; Primitive neural stem cells; Spinal cord injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / metabolism*
  • Animals
  • Cell Proliferation
  • Cell Separation
  • Colony-Forming Units Assay
  • Forkhead Transcription Factors / metabolism
  • Glial Fibrillary Acidic Protein / metabolism
  • Mice, Mutant Strains
  • Mice, Transgenic
  • Myelin Basic Protein / metabolism*
  • Myelin Sheath / metabolism
  • Nestin / metabolism
  • Neural Stem Cells / cytology*
  • Neural Stem Cells / metabolism*
  • Octamer Transcription Factor-3 / metabolism
  • Spheroids, Cellular / cytology
  • Spinal Cord / cytology*
  • Spinal Cord Injuries / pathology

Substances

  • FOXJ1 protein, mouse
  • Forkhead Transcription Factors
  • Glial Fibrillary Acidic Protein
  • Myelin Basic Protein
  • Nestin
  • Octamer Transcription Factor-3

Grants and funding