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You searched for subject:(skeleton stem cell). Showing records 1 – 2 of 2 total matches.

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Columbia University

1. Moore, Emily. The primary cilium encourages osteogenic behavior in periosteal osteochondroprogenitors and osteocytes during juvenile skeletal development and adult bone adaptation.

Degree: 2018, Columbia University

Primary cilia are sensory organelles that facilitate early skeletal development, as well as maintenance and adaptation of bone later in life. These solitary, immotile organelles are known to be involved in cell differentiation, proliferation, and mechanotransduction, a process by which cells sense and covert external physical stimuli into intracellular biochemical signals. Bone is a metabolically active tissue that continuously recruits osteogenic precursors and relies on osteocytes, the sensory cells of bone, to coordinate skeletal maintenance. Overall bone quality is dependent on the integrity of the initial structure formed, as well as this organ’s ability to adapt to physical loads. Proper differentiation and controlled proliferation of osteogenic progenitors are critical to the initial formation of the skeleton, while osteocyte mechanotransduction is essential for adaptation of developed bone. These phenomena rely on primary cilia, but little is known about the origin of osteogenic precursors and the ciliary mechanisms that promote osteogenesis. In this thesis, we first characterize an osteochondroprogenitor (OCP) population that rapidly and extensively populates skeletal tissues during juvenile skeletal development (Chapter 2). We also demonstrate that the primary cilium is critical for these cells to differentiate and contribute to skeletogenesis. We then show this OCP population is required for adult bone adaptation and is mechanoresponsive (Chapter 3). Again, we demonstrate that primary cilia are necessary for these OCPs to sense physical stimuli and differentiate into active bone-forming cells. Finally, we identify a novel link between ciliary calcium and cAMP dynamics in the osteocyte primary cilium (Chapter 4). Specifically, we show that a calcium channel (TRPV4) and adenylyl cyclases, which produce cAMP, bind calcium to mediate calcium entry and cAMP production, respectively, and these phenomena are critical to fluid flow-induced osteogenesis. Collectively, our results demonstrate that an easily extracted progenitor population is pre-programmed towards an osteogenic fate and extensively contributes to bone generation through primary cilium-mediated mechanisms at multiple stages of life. Furthermore, we identified ciliary proteins that are potentially unique to the osteocyte and can be manipulated to encourage osteogenesis by tuning calcium/ cAMP dynamics. For these reasons, we propose that this OCP population and their primary cilia, as well as osteocyte ciliary proteins that coordinate calcium/ cAMP dynamics, are attractive therapeutic targets to encourage bone regeneration.

Subjects/Keywords: Biomedical engineering; Bones – Growth; Stem cells; Cell organelles; Skeleton – Growth

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Moore, E. (2018). The primary cilium encourages osteogenic behavior in periosteal osteochondroprogenitors and osteocytes during juvenile skeletal development and adult bone adaptation. (Doctoral Dissertation). Columbia University. Retrieved from https://doi.org/10.7916/D8JW9RVP

Chicago Manual of Style (16th Edition):

Moore, Emily. “The primary cilium encourages osteogenic behavior in periosteal osteochondroprogenitors and osteocytes during juvenile skeletal development and adult bone adaptation.” 2018. Doctoral Dissertation, Columbia University. Accessed December 15, 2019. https://doi.org/10.7916/D8JW9RVP.

MLA Handbook (7th Edition):

Moore, Emily. “The primary cilium encourages osteogenic behavior in periosteal osteochondroprogenitors and osteocytes during juvenile skeletal development and adult bone adaptation.” 2018. Web. 15 Dec 2019.

Vancouver:

Moore E. The primary cilium encourages osteogenic behavior in periosteal osteochondroprogenitors and osteocytes during juvenile skeletal development and adult bone adaptation. [Internet] [Doctoral dissertation]. Columbia University; 2018. [cited 2019 Dec 15]. Available from: https://doi.org/10.7916/D8JW9RVP.

Council of Science Editors:

Moore E. The primary cilium encourages osteogenic behavior in periosteal osteochondroprogenitors and osteocytes during juvenile skeletal development and adult bone adaptation. [Doctoral Dissertation]. Columbia University; 2018. Available from: https://doi.org/10.7916/D8JW9RVP


University of Michigan

2. Pineault, Kyriel. Hox11-Expression Defines a Skeletal Mesenchymal Stem Cell that Contributes to Skeleton Development, Growth, and Repair.

Degree: PhD, Cell and Developmental Biology, 2018, University of Michigan

The skeleton is one of the most widely explored organs for defining mesenchymal stem/progenitor cell (MSC) populations, and there is significant interest in MSCs for their potential in novel and potentially curative therapies for a variety of musculoskeletal disorders. The skeleton is a highly dynamic tissue and MSCs function as a reservoir of new cellular material to support skeletal growth, turnover, and repair. Using a Hoxa11eGFP reporter allele, recent work demonstrated Hox11-expressing cells in the adult skeleton are identified as an MSC-enriched population in the bone marrow and on the cortical bone surfaces. In fact, at all stages examined Hoxa11eGFP-expression is excluded from all differentiated skeletal cell types. Developmentally, Hox genes are critically important patterning regulators and function regionally along the axes of the mammalian skeleton. The Hox11 genes specifically function to pattern the lumbar spine and zeugopod region (radius/ulna and tibia/fibula) of the limb. In addition to classical functions for Hox genes during development, ongoing work has revealed continuing functions for Hox11 during skeletal growth and adult injury repair. Given the continuum of Hox11-expression in undifferentiated stromal cells and the genetic evidence for Hox11 function at all stages, I investigated the possibility that Hox11-expression may identify a skeletal progenitor population throughout the life of the animal. These studies aimed to understand the lineage-relationship of Hox11-expressing stromal cells from embryonic to adult stages and to test the skeletal progenitor potential of this population over time. The first evidence to support the hypothesis that Hox11-expressing cells are skeletal progenitors at all stages, was flow cytometry data demonstrating that Hoxa11eGFP-expressing cells co-express adult MSC markers PDGFRα/CD51 and Leptin Receptor (LepR) throughout life, beginning from embryonic stages. To rigorously investigate the skeletal progenitor potential of this population in vivo, I generated a Hoxa11-CreERT2 allele by Cas9/CRISPR genetic engineering. I demonstrate that Hoxa11-lineage marked cells are multi-potent in vivo and contribute to all mesenchymal cell types of the skeleton; cartilage, bone, and adipose. Hoxa11-lineage marked cells continue to contribute to new skeletal cells out to at least one year of age. In addition to giving rise to the skeleton, Hoxa11-lineage marked stromal cells persist within the bone marrow and on the bone surfaces throughout life, even from embryonic stages. Lineage-marked stromal cells co-express MSC markers PDGFRα/CD51 and LepR and continue to express Hoxa11eGFP at all time points. The expression of Hoxa11eGFP within Hoxa11-lineage marked MSCs throughout life, and the continuous contribution to new skeletal cells provides evidence that Hox11-expressing MSCs are self-renewing skeletal stem cells. These data reconcile conflicting reports in the field regarding when MSCs arise and provide definitive genetic evidence for an embryonic, perichondrial origin for… Advisors/Committee Members: Spence, Jason (committee member), Allen, Benjamin (committee member), Lin, Jiandie (committee member), Lucas-Alcaraz, Daniel (committee member), Wellik, Deneen Marie (committee member).

Subjects/Keywords: Hox genes; skeleton stem cell; mesenchymal stem/stromal cell (MSC); skeletal patterning; lineage-trace; developmental biology; Molecular, Cellular and Developmental Biology; Science

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Pineault, K. (2018). Hox11-Expression Defines a Skeletal Mesenchymal Stem Cell that Contributes to Skeleton Development, Growth, and Repair. (Doctoral Dissertation). University of Michigan. Retrieved from http://hdl.handle.net/2027.42/147658

Chicago Manual of Style (16th Edition):

Pineault, Kyriel. “Hox11-Expression Defines a Skeletal Mesenchymal Stem Cell that Contributes to Skeleton Development, Growth, and Repair.” 2018. Doctoral Dissertation, University of Michigan. Accessed December 15, 2019. http://hdl.handle.net/2027.42/147658.

MLA Handbook (7th Edition):

Pineault, Kyriel. “Hox11-Expression Defines a Skeletal Mesenchymal Stem Cell that Contributes to Skeleton Development, Growth, and Repair.” 2018. Web. 15 Dec 2019.

Vancouver:

Pineault K. Hox11-Expression Defines a Skeletal Mesenchymal Stem Cell that Contributes to Skeleton Development, Growth, and Repair. [Internet] [Doctoral dissertation]. University of Michigan; 2018. [cited 2019 Dec 15]. Available from: http://hdl.handle.net/2027.42/147658.

Council of Science Editors:

Pineault K. Hox11-Expression Defines a Skeletal Mesenchymal Stem Cell that Contributes to Skeleton Development, Growth, and Repair. [Doctoral Dissertation]. University of Michigan; 2018. Available from: http://hdl.handle.net/2027.42/147658

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