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Extrinsic and Intrinsic Signalling Pathways That Regulate Stem Cell Developmental PotentialPrice, Feodor duPasquier 21 August 2012 (has links)
Instructive signals, whether external or internal, play critical roles in regulating the developmental potency or ability to self-renew of stem cells. External signals may range from secreted growth factors to extracellular matrix proteins found in the stem cell niche. Internal signals include activated signalling cascades and the eventual transcriptional mechanisms they initiate. In either fashion, stem cells are regulated in a complex temporal and context specific manner in order to maintain or maximise their unique characteristics. Previous experiments suggest that Wnt3a plays a role in maintaining the pluripotent state of mouse embryonic stem (mES) cells. However, in the absence of leukemia inhibitory factor (LIF), Wnt signalling is unable to maintain ES cells in the undifferentiated state. This implies that maintaining the pluripotent state of mES cells is not the primary function of canonical Wnt signalling. To further characterize the role of Wnt3a in pluripotency and lineage specification undifferentiated and differentiated mES cells were induced with Wnt3a. Wnt3a induced the formation of a metastable primitive endoderm state and upon subsequent differentiation, the induction of large quantities of visceral endoderm. Furthermore, we determined that the ability of Wnt3a to induce a metastable primitive endoderm state was mediated by the T-box transcription factor Tbx3. Our data demonstrates a novel role for Wnt3a in promoting the interconversion of undifferentiated mES cells into a pluripotent primitive endoderm state. Aging of skeletal muscle tissue is accompanied by fibrosis, atrophy and remodeling all of which negatively affect muscle performance. Whether this reduction in skeletal muscle competency is directly attributed to a resident adult stem cell population called satellite cells remains largely unknown. Here, we undertook an investigation into how age affects the transcriptional profile of satellite cells and their repopulating ability following transplantation. We determined that as satellite cells age, both their regenerative capacity and ability to colonize the satellite cell niche is reduced. Additionally, we identified satellite cell specific transcriptional profiles that differed with respect to age. Therefore, we conclude that intrinsic factors are an important determinant of satellite cell regenerative capacity during the aging process.
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Expression profile of Wnt isoforms during differentiation of aging C2C12 myoblast cells.Lin, Chien-Yu. January 2010 (has links)
Satellite cells are known as the definitive muscle stem cells and are responsible for
skeletal muscle maintenance and repair. The capacity of these satellite cells to
participate in myogenesis decreases with age and as a result, muscle repair and
maintenance in an aging organism is characterized by fibrosis, lipid accumulation and
atrophy, a process known as sarcopenia. Recent parabiotic studies have shown that
satellite cells with reduced myogenic capability in aging muscle can be rejuvenated to
undergo effective myogenesis when exposed to a young environment. Further analysis
has suggested that the Wnt family of signaling proteins identified in serum is pivotal in
regulating cell fate, proliferation and differentiation, during aging. Wnt3a is known to
regulate fibrogenensis, Wnt10b adipogenesis and Wnt7 myogenesis. In the current
study, we aim to determine the cytosolic and secreted expression profiles of the three
Wnt isoforms, Wnt3a, 7 and 10b, during myogenesis of early and late passage C2C12
myoblasts. We then extend our analysis to determine whether conditioned media
could improve the myogenic capacity of late passage cells.
Late passage C2C12 cells had elevated Wnt3a cytosolic levels along with reduced
differentiation capacity and a rapidly declining Wnt7 levels, in comparison to early
passage cells. The elevated Wnt3a suggests an elevated fibrogenic predisposition,
whereas the declining Wnt7 cytosolic levels, a decrease in myogenic capacity.
Furthermore, analysis of the secreted vs. cytosolic ratio in Wnt7 levels revealed a more
rapid decline in late vs. early passage cells during differentiation, supporting the
observed decreased myogenic ability. Moreover, late passage cells also showed lower
Wnt10b levels compared to early passage cells. This low level of Wnt10b is likely
associated with an increase in adipogenic predisposition. The results obtained in the
cross-over experiments indicated that conditioned media from early passage cells did
not improve the differentiation of late passage cells by the low levels of Myogenin and
MHC. However, early passage cells treated with conditioned media from late passage
cells surprisingly showed a marginal increase in both Myogenin and MHC levels.
Interestingly, cytosolic Wnt3a and 7 in late passage cells treated with ‘young media’
were increased compared to control whereas early passage cells treated with ‘old’
media showed significantly decreased levels of Wnt3a and 7. Furthermore, early
passage cells acquired a declining expression when treated with ‘young’ media
whereas late passage cells had an increasing level when treated with ‘old’ media. This
indicates a possible improvement in differentiation in late passage cells.
Taken together, our results support a role for Wnt7 and Wnt10b in promoting
myogenesis while Wnt3a may decrease myogenesis. With the increase in passage
numbers, the reduced myogenic predisposition is regulated by reduced Wnt10b, 7 and
elevated Wnt3a levels, respectively. Moreover, we speculate that the lack of myogenic
improvement in the cross-over experiment could be the presence of unknown secreted
factors in ‘young’ media that impedes myogenesis. Finally, cell lines are known to be
biologically different to primary myoblasts through the accumulation of mutations
which could render the cells less sensitive to growth factors. Therefore, it is imperative
that the current study is repeated with primary culture myoblasts. / Thesis (M.Sc.)-University of KwaZulu-Natal, Pietermaritzburg, 2010.
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Identification of multiple roles for Wnt signaling during mouse developmentMohamed, Othman January 2004 (has links)
Signaling molecules play essential roles in communication between cells. Wnt signaling molecules are critical for embryonic development of several organisms. I examined the involvement of Wnt signaling during two major developmental processes, namely embryo implantation and formation of the embryonic body axes. Using RT-PCR analysis, I showed that multiple Wnt genes are expressed in the blastocyst at the time of implantation. Moreover, expression of Wnt 11 requires both estrogen produced by the mother and the uterine environment. Using a transgenic approach, I showed that beta-catenin-regulated transcriptional activity, which is a major transducer of Wnt signaling, is activated in the uterus specifically at the site of implantation in an embryo-dependent manner. These results introduce Wnts as candidate signaling factors that may mediate the communication between the embryo and uterus that initiates implantation. / Wnt/beta-catenin signaling triggers axis formation in Xenopus and zebrafish embryos. I showed that, during embryonic development, beta-catenin-regulated transcriptional activity is first detected in the prospective primitive streak region prior to gastrulation. This demarcates the posterior region of the embryo. This activity then becomes restricted to the elongating primitive streak and to the node. In Xenopus embryos, beta-catenin participates in the formation of the organizer through the activation of the homeodomain transcription factors Siamois and Twin. I obtained evidence that a Siamois/Twin-like binding activity exists in mouse embryos and is localized in the node. These results strongly suggest that, as the case in Xenopus and zebrafish, the Wnt/beta-catenin pathway is involved in establishing embryonic body axes. / Furthermore, using the transgenic mouse line that I generated for these studies, I mapped the transcriptional activity of beta-catenin during mouse embryonic development. These results revealed when and where this activity, and presumably Wnt signaling, is active during the development of several organs and embryonic structures.
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Transcriptional regulation by distinct Wnt signaling pathways in melanoma /Shah, Kavita Virendra. January 2007 (has links)
Thesis (Ph. D.)--University of Washington, 2007. / Vita. Includes bibliographical references (leaves 133-173).
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Bili, a conserved FERM domain containing protein negatively regulates Wnt/beta-catenin signaling /Kategaya, Lorna Sonia. January 2007 (has links)
Thesis (Ph. D.)--University of Washington, 2007. / Vita. Includes bibliographical references (leaves 44-52).
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Expression of Wnt signaling targets and their clinico-pathological significance in colorectal neoplasm a tissue microarray study /Guo, Dongli. January 2006 (has links)
Thesis (Ph. D.)--University of Hong Kong, 2007. / Title proper from title frame. Also available in printed format.
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Feedback Regulation of Wnt Signaling by Naked Cuticle (Nkd) during Drosophila EmbryogenesisChan, Chih-Chiang January 2008 (has links)
Dissertation (Ph.D.) -- University of Texas Southwestern Medical Center at Dallas, 2008. / Vita. Bibliography: p.166-179
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Large scale CpG island methylation profiling of small B cell lymphomaRahmatpanah, Farahnaz B. Caldwell, Charles W., January 2008 (has links)
The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. Title from PDF of title page (University of Missouri--Columbia, viewed on April 1, 2010). Vita. Thesis advisor: Charles W. Caldwell. "May 2008" Includes bibliographical references
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Strukturelle und funktionelle Charakterisierung des Knochenwachstums-Modulators SclerostinWeidauer, Stella Elisabeth. Unknown Date (has links)
Univ., Diss., 2010--Würzburg.
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Wnt regulated transcription factor networks mediate vertebrate cardiogenesisMartin, Jennifer. January 2009 (has links)
Thesis (Ph.D.)--Aberdeen University, 2009. / Title from web page (viewed on June 26, 2009). Includes bibliographical references.
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