Regionally Restricted Hox Function in Adult Bone Marrow Multipotent Mesenchymal Stem/Stromal Cells
| Autor: | Danielle Rux, Ilea T. Swinehart, Deneen M. Wellik, Daniel Lucas, S. A. Goldstein, Jane Y. Song, Kenneth M. Kozloff, Kyriel M. Pineault, Kelsey Trulik, Aleesa J. Schlientz |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Aging animal structures Stromal cell Green Fluorescent Proteins Bone Marrow Cells Biology General Biochemistry Genetics and Molecular Biology 03 medical and health sciences medicine Animals Limb development Tibia Hox gene Molecular Biology Fracture Healing Homeodomain Proteins Mesenchymal stem cell Embryogenesis Cell Differentiation Mesenchymal Stem Cells Cell Biology Anatomy Chondrogenesis Cell biology Mice Inbred C57BL 030104 developmental biology medicine.anatomical_structure Animals Newborn Bone marrow Developmental Biology |
| Zdroj: | Developmental Cell. 39:653-666 |
| ISSN: | 1534-5807 |
| DOI: | 10.1016/j.devcel.2016.11.008 |
| Popis: | Posterior Hox genes (Hox9-13) are critical for patterning the limb skeleton along the proximodistal axis during embryonic development. Here we show that Hox11 paralogous genes, which developmentally pattern the zeugopod (radius/ulna and tibia/fibula), remain regionally expressed in the adult skeleton. Using Hoxa11EGFP reporter mice, we demonstrate expression exclusively in multipotent mesenchymal stromal cells (MSCs) in the bone marrow of the adult zeugopod. Hox-positive cells express PDGFRα and CD51, are marked by LepR-Cre, and exhibit colony-forming unit fibroblast activity and tri-lineage differentiation in vitro. Loss of Hox11 function leads to fracture repair defects, including reduced cartilage formation and delayed ossification. Hox mutant cells are defective in osteoblastic and chondrogenic differentiation in tri-lineage differentiation experiments, and these defects are zeugopod specific. In the stylopod (humerus and femur) and sternum, bone marrow MSCs express other regionally restricted Hox genes, and femur fractures heal normally in Hox11 mutants. Together, our data support regional Hox expression and function in skeletal MSCs. |
| Databáze: | OpenAIRE |
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