Secretion of Shh by a Neurovascular Bundle Niche Supports Mesenchymal Stem Cell Homeostasis in the Adult Mouse Incisor

TY - JOUR

T1 - Secretion of Shh by a Neurovascular Bundle Niche Supports Mesenchymal Stem Cell Homeostasis in the Adult Mouse Incisor

AU - Zhao, Hu

AU - Feng, Jifan

AU - Seidel, Kerstin

AU - Shi, Songtao

AU - Klein, Ophir

AU - Sharpe, Paul

AU - Chai, Yang

PY - 2014/2/6

Y1 - 2014/2/6

N2 - Mesenchymal stem cells (MSCs) are typically defined by their in vitro characteristics, and as a consequence the in vivo identity of MSCs and their niches are poorly understood. To address this issue, we used lineage tracing in a mouse incisor model and identified the neurovascular bundle (NVB) as an MSC niche. We found that NVB sensory nerves secrete Shh protein, which activates Gli1 expression in periarterial cells that contribute to all mesenchymal derivatives. These periarterial cells do not express classical MSC markers used to define MSCs in vitro. In contrast, NG2(+) pericytes represent an MSC subpopulation derived from Gli1+ cells; they express classical MSC markers and contribute little to homeostasis but are actively involved in injury repair. Likewise, incisor Gli1(+) cells, but not NG2(+) cells, exhibit typical MSC characteristics in vitro. Collectively, we demonstrate that MSCs originate from periarterial cells and are regulated by Shh secretion from an NVB.

AB - Mesenchymal stem cells (MSCs) are typically defined by their in vitro characteristics, and as a consequence the in vivo identity of MSCs and their niches are poorly understood. To address this issue, we used lineage tracing in a mouse incisor model and identified the neurovascular bundle (NVB) as an MSC niche. We found that NVB sensory nerves secrete Shh protein, which activates Gli1 expression in periarterial cells that contribute to all mesenchymal derivatives. These periarterial cells do not express classical MSC markers used to define MSCs in vitro. In contrast, NG2(+) pericytes represent an MSC subpopulation derived from Gli1+ cells; they express classical MSC markers and contribute little to homeostasis but are actively involved in injury repair. Likewise, incisor Gli1(+) cells, but not NG2(+) cells, exhibit typical MSC characteristics in vitro. Collectively, we demonstrate that MSCs originate from periarterial cells and are regulated by Shh secretion from an NVB.

KW - SUPERIOR CERVICAL GANGLIONECTOMY

KW - INFERIOR ALVEOLAR NERVE

KW - STROMAL CELLS

KW - PROGENITOR CELLS

KW - SONIC-HEDGEHOG

KW - RAT INCISOR

KW - BONE-MARROW

KW - ARTERIAL DIFFERENTIATION

KW - PERIVASCULAR CELLS

KW - DENTAL-PULP

U2 - 10.1016/j.stem.2013.12.013

DO - 10.1016/j.stem.2013.12.013

M3 - Article

SN - 1934-5909

VL - 14

SP - 160

EP - 173

JO - Cell Stem Cell

JF - Cell Stem Cell

IS - 2

ER -