Vasculature-Associated Cells Expressing Nestin in Developing Bones Encompass Early Cells in the Osteoblast and Endothelial Lineage

• Published in: Developmental cell Vol. 29; no. 3; pp. 330 - 339
• Main Authors: Ono, Noriaki, Ono, Wanida, Mizoguchi, Toshihide, Nagasawa, Takashi, Frenette, Paul S., Kronenberg, Henry M.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 12-05-2014
• Subjects: Animals; Bone and Bones - embryology; Bone and Bones - metabolism; Cell Lineage; Core Binding Factor Alpha 1 Subunit - biosynthesis; Core Binding Factor Alpha 1 Subunit - genetics; Endothelial Cells - cytology; Endothelial Cells - metabolism; Green Fluorescent Proteins - genetics; Hedgehog Proteins - biosynthesis; Hedgehog Proteins - genetics; Hematopoiesis; Mice; Mice, Knockout; Nestin - genetics; Nestin - metabolism; Osteoblasts - cytology; Promoter Regions, Genetic
• ISSN: 1534-5807; 1878-1551
• DOI: 10.1016/j.devcel.2014.03.014

Nestin-positive (Nes+) cells are important hematopoiesis-supporting constituents in adult bone marrow. However, how these cells originate during endochondral bone development is unknown. Studies using mice expressing GFP under the direction of nestin promoter/enhancer (Nes-GFP) revealed distinct endothelial and nonendothelial Nes+ cells in the embryonic perichondrium; the latter were early cells of the osteoblast lineage immediately descended from their progenitors upon Indian hedgehog action and Runx2 expression. During vascular invasion and formation of ossification centers, these Nes+ cells were closely associated with each other and increased in number progressively. Interestingly, cells targeted by tamoxifen-inducible cre recombinase driven by nestin enhancer (Nes-creER) in developing bone marrow were predominantly endothelial cells. Furthermore, Nes+ cells in postnatal bones were heterogeneous populations, including a range of cells in the osteoblast and endothelial lineage. These findings reveal an emerging complexity of stromal populations, accommodating Nes+ cells as vasculature-associated early cells in the osteoblast and endothelial lineage.
•Endothelial and nonendothelial nestin+ cells develop in endochondral ossification•Ihh and Runx2 action is needed for nestin+ cells to become osteoblasts•Endothelial cells are preferentially targeted by Nes-creER in developing marrow•Nestin+ cells in developing bones are a heterogeneous stromal cell population
Nes+ cells are hematopoiesis-supporting constituents in adult bone marrow. Ono et al. find distinct endothelial and nonendothelial Nes+ cells in growing bones; the latter developed as immediate descendants from their precursors upon Indian hedgehog action and Runx2 expression in the embryonic perichondrium, revealing an emerging complexity of stromal populations.