Neural microvascular pericytes contribute to human adult neurogenesis

J Comp Neurol. 2019 Mar 1;527(4):780-796. doi: 10.1002/cne.24565. Epub 2018 Nov 23.

Abstract

Consistent adult neurogenic activity in humans is observed in specific niches within the central nervous system. However, the notion of an adult neurogenic niche is challenged by accumulating evidence for ectopic neurogenic activity in other cerebral locations. Herein we interface precision of ultrastructural resolution and anatomical simplicity of accessible human dental pulp neurogenic zone to address this conflict. We disclose a basal level of adult neurogenic activity characterized by glial invasion of terminal microvasculature followed by release of individual platelet-derived growth factor receptor-β mural pericytes and subsequent reprogramming into NeuN+ local interneurons. Concomitant angiogenesis, a signature of adult neurogenic niches, accelerates the rate of neurogenesis by amplifying release and proliferation of the mural pericyte population by ≈10-fold. Subsequent in vitro and in vivo experiments confirmed gliogenic and neurogenic capacities of human neural pericytes. Findings foreshadow the bimodal nature of the glio-vascular assembly where pericytes, under instruction from glial cells, can stabilize the quiescent microvasculature or enrich local neuronal microcircuits upon differentiation.

Keywords: RRID:AB_10013382; RRID:AB_10013383; RRID:AB_10711153; RRID:AB_1603338; RRID:AB_2251134; RRID:AB_2314899; RRID:AB_2341193; RRID:AB_300723; RRID:AB_305407; RRID:AB_306863; RRID:AB_444319; RRID:AB_445175; RRID:AB_448990; RRID:AB_476828; RRID:AB_732011; RRID:AB_732415; RRID:IMSR_JAX:003145; angiogenesis; human adult neurogenesis; pericytes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Cell Differentiation / physiology*
  • Dental Pulp / cytology
  • Female
  • Humans
  • Interneurons / cytology*
  • Male
  • Mice
  • Neural Stem Cells / cytology*
  • Neurogenesis / physiology*
  • Pericytes / cytology*
  • Stem Cell Niche / physiology
  • Young Adult