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You searched for +publisher:"University of Michigan" +contributor:("Wellik, Deneen Marie"). Showing records 1 – 2 of 2 total matches.

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University of Michigan

1. 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 14, 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. 14 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 14]. 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


University of Michigan

2. Rux, Danielle. Hox11 function in Region-Specific Adult Mesenchymal Stem/Stromal Cells is Required for Fracture Repari.

Degree: PhD, Cell and Developmental Biology, 2016, University of Michigan

The mammalian skeleton boasts a remarkable capacity to completely restore the original structure and function of a bone following injury. Interestingly, the biological processes of fracture repair recapitulate many of the mechanisms of embryonic skeletal development. The Hox genes are critical regulators of skeletal development, yet the function of these genes during adult fracture repair is largely unknown. Ongoing research in the Wellik lab is focused on understanding the role(s) of these genes in this context. The Hox genes encode evolutionarily conserved transcription factors that are imperative for patterning of the axial and limb skeleton in the developing embryo. Specifically, Hox11 genes function to instruct growth and morphology of the lumbar elements of the axial skeleton and the zeugopod elements (radius/ulna and tibia/fibula) of the limbs. Previous work using a Hoxa11eGFP allele showed that Hox11 is expressed through the latest stages of embryonic development. We have now discovered that Hox11 genes continue to be expressed in the adult skeleton and are largely restricted to the previously characterized PDGFRα+/CD51+/Leptin Receptor(LepR)+ mesenchymal stem/stromal cell (MSC) population in bone marrow. These Hox11-expressing MSCs expand in response to fracture injury and are maintained throughout repair. Loss of Hox11 function results in a significantly reduced ability to generate cartilage early in repair, and at late stages, the hard callus persists and is incompletely remodeled. Together, our data suggests that Hox11 functions in MSCs at multiple stages of repair, first, for endochondral ossification and later for bone remodeling. In addition, we show more generally that the Hox expression pattern established during embryonic development is maintained in the adult skeleton. Overall, this research provides novel evidence that Hox genes have critical roles beyond embryonic patterning and that these genes are expressed and function in adult MSCs. Advisors/Committee Members: Allen, Benjamin (committee member), Franceschi, Renny T (committee member), Jepsen, Karl John (committee member), Lucas-Alcaraz, Daniel (committee member), McCauley, Laurie Kay (committee member), Wellik, Deneen Marie (committee member).

Subjects/Keywords: Hox11 Genes in Adult MSCs for Fracture Repair; Molecular, Cellular and Developmental Biology; Science

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

APA (6th Edition):

Rux, D. (2016). Hox11 function in Region-Specific Adult Mesenchymal Stem/Stromal Cells is Required for Fracture Repari. (Doctoral Dissertation). University of Michigan. Retrieved from http://hdl.handle.net/2027.42/135754

Chicago Manual of Style (16th Edition):

Rux, Danielle. “Hox11 function in Region-Specific Adult Mesenchymal Stem/Stromal Cells is Required for Fracture Repari.” 2016. Doctoral Dissertation, University of Michigan. Accessed December 14, 2019. http://hdl.handle.net/2027.42/135754.

MLA Handbook (7th Edition):

Rux, Danielle. “Hox11 function in Region-Specific Adult Mesenchymal Stem/Stromal Cells is Required for Fracture Repari.” 2016. Web. 14 Dec 2019.

Vancouver:

Rux D. Hox11 function in Region-Specific Adult Mesenchymal Stem/Stromal Cells is Required for Fracture Repari. [Internet] [Doctoral dissertation]. University of Michigan; 2016. [cited 2019 Dec 14]. Available from: http://hdl.handle.net/2027.42/135754.

Council of Science Editors:

Rux D. Hox11 function in Region-Specific Adult Mesenchymal Stem/Stromal Cells is Required for Fracture Repari. [Doctoral Dissertation]. University of Michigan; 2016. Available from: http://hdl.handle.net/2027.42/135754

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