Adult DRG Stem/Progenitor Cells Generate Pericytes in the Presence of Central Nervous System (CNS) Developmental Cues, and Schwann Cells in Response to CNS Demyelination

Stem Cells. 2015 Jun;33(6):2011-24. doi: 10.1002/stem.1997. Epub 2015 Apr 21.

Abstract

It has been proposed that the adult dorsal root ganglia (DRG) harbor neural stem/progenitor cells (NPCs) derived from the neural crest. However, the thorough characterization of their stemness and differentiation plasticity was not addressed. In this study, we investigated adult DRG-NPC stem cell properties overtime, and their fate when ectopically grafted in the central nervous system. We compared them in vitro and in vivo to the well-characterized adult spinal cord-NPCs derived from the same donors. Using micro-dissection and neurosphere cultures, we demonstrate that adult DRG-NPCs have quasi unlimited self-expansion capacities without compromising their tissue specific molecular signature. Moreover, they differentiate into multiple peripheral lineages in vitro. After transplantation, adult DRG-NPCs generate pericytes in the developing forebrain but remyelinating Schwann cells in response to spinal cord demyelination. In addition, we show that axonal and endothelial/astrocytic factors as well astrocytes regulate the fate of adult DRG-NPCs in culture. Although the adult DRG-NPC multipotency is restricted to the neural crest lineage, their dual responsiveness to developmental and lesion cues highlights their impressive adaptive and repair potentials making them valuable targets for regenerative medicine.

Keywords: Adult dorsal root ganglia stem cells; Central nervous system; Differentiation plasticity; Myelin-forming cells; Pericytes; Repair.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult Stem Cells / cytology
  • Animals
  • Cell Differentiation / physiology*
  • Cells, Cultured
  • Demyelinating Diseases / pathology*
  • Demyelinating Diseases / therapy
  • Ganglia, Spinal / cytology*
  • Ganglia, Spinal / metabolism
  • Mice, Inbred C57BL
  • Mice, Nude
  • Myelin Sheath / metabolism*
  • Nerve Regeneration / physiology
  • Neural Crest / cytology
  • Neurons / cytology
  • Pericytes / cytology*
  • Schwann Cells / cytology*