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Axonal Outgrowth and Pathfinding of Human Pluripotent Stem Cell-Derived Retinal Ganglion CellsFligor, Clarisse 08 1900 (has links)
Indiana University-Purdue University Indianapolis (IUPUI) / Retinal ganglion cells (RGCs) serve as a vital connection between the eye and the brain with damage to their axons resulting in loss of vision and/or blindness. Reti- nal organoids are three-dimensional structures derived from human pluripotent stem cells (hPSCs) which recapitulate the spatial and temporal differentiation of the retina, providing a valuable model of RGC development in vitro. The working hypothesis of these studies is that hPSC-derived RGCs are capable of extensive outgrowth and display target specificity and pathfinding abilities. Initial efforts focused on charac- terizing RGC differentiation throughout early stages of organoid development, with a clearly defined RGC layer developing in a temporally-appropriate manner express- ing a compliment of RGC-associated markers. Beyond studies of RGC development, retinal organoids may also prove useful to investigate and model the extensive axonal outgrowth necessary to reach post-synaptic targets. As such, additional efforts aimed to elucidate factors promoting axonal outgrowth. Results demonstrated significant enhancement of axonal outgrowth through modulation of both substrate composi- tion and growth factor signaling. Furthermore, RGCs possessed guidance receptors that are essential in influencing outgrowth and pathfinding. Subsequently, to de- termine target specificity, aggregates of hPSC-derived RGCs were co-cultured with explants of mouse lateral geniculate nucleus (LGN), the primary post-synaptic target of RGCs. Axonal outgrowth was enhanced in the presence of LGN, and RGCs dis- played recognition of appropriate targets, with the longest neurites projecting towards LGN explants compared to control explants or RGCs grown alone. Generated from
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the fusion of regionally-patterned organoids, assembloids model projections between distinct regions of the nervous system. Therefore, final efforts of these studies focused upon the generation of retinocortical assembloids in order to model the long-distance outgrowth characteristic of RGCs. RGCs displayed extensive axonal outgrowth into cortical organoids, with the ability to respond to environmental cues. Collectively, these results establish retinal organoids as a valuable tool for studies of RGC develop- ment, and demonstrate the utility of organoid-derived RGCs as an effective platform to study factors influencing outgrowth as well as modeling long-distance projections and pathfinding abilities.
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Leptin Receptor, a Surface Marker for a Subset of Highly Engrafting Long-Term Functional Hematopoietic Stem CellsTrinh, Thao Le Phuong 04 1900 (has links)
Indiana University-Purdue University Indianapolis (IUPUI) / The entire hematopoietic system rests upon a group of very rare cells called hematopoietic stem cells (HSCs). Due to this extraordinarily crucial role, after birth HSCs are localized to the deep bone marrow niche, a hypoxic environment inside the bone where HSCs are under well-orchestrated regulation by both cellular and humoral factors. Among the cellular components regulating hematopoiesis are Leptin Receptor (LEPR)-expressing mesenchymal/stromal cells and adipocytes; both have been demonstrated to have significant influence on the maintenance of HSCs under homeostasis and in stress-related conditions. It has been reported in early work by others that HSCs and hematopoietic progenitor cells (HPCs) express LEPR. However, whether LEPR+ HSCs/HPCs are functionally different from other HSCs/HPCs was unknown. In this study, I demonstrated for the first time that murine LEPR+ Lineage-Sca-1+cKit+ (LSK, a heterogenous population consisting of HSCs/HPCs) cells even though constituting a small portion of total LSK cells are significantly enriched for both phenotypic and functional self-renewing long-term (LT) HSCs as shown in primary and secondary transplants in lethally irradiated recipients. LEPR+LSK cells are also more enriched for colony-forming progenitor cells assessed by colony-forming unit (CFU) assays. In addition, LEPR+ HSCs (defined as LSKCD150+CD48-) exhibited robust repopulating potential as compared to LEPR-HSCs in long-term competitive transplantation assays. To elucidate the molecular pathways that may govern functional properties of LEPR+HSCs, bulk RNA-seq on freshly sorted cells was done. Gene set enrichment analyses (GSEA) revealed Interferon Type I and Interferon γ (IFNγ) Pathways were significantly enriched in LEPR+HSCs while mitochondrial membrane protein gene set was significantly enriched in LEPR-HSCs. Interestingly, proinflammatory signaling including IFNγ pathway has been suggested to be critical for the emergence of embryonic HSCs from the hemogenic endothelium.
Altogether, our work demonstrated that LEPR+HSCs represent a small subset of highly engrafting adult BM HSCs. These results may have potential therapeutic implications in the field of hematopoietic transplantation as LEPR is highly conserved between mice and humans.
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Two distinct roles of the yorkie/yap gene during homeostasis in the planarian Dugesia japonica / Dugesia japonicaプラナリアでyorkie/yap遺伝子の2つの機能Hwang, Byulnim 23 March 2015 (has links)
京都大学 / 0048 / 新制・課程博士 / 博士(理学) / 甲第18838号 / 理博第4096号 / 新制||理||1589(附属図書館) / 31789 / 京都大学大学院理学研究科生物科学専攻 / (主査)教授 阿形 清和, 教授 杤尾 豪人, 教授 森 和俊 / 学位規則第4条第1項該当 / Doctor of Science / Kyoto University / DFAM
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Early osteoinductive human bone marrow mesenchymal stromal/stem cells support an enhanced hematopoietic cell expansion with altered chemotaxis- and adhesion-related gene expression profiles / 骨分化誘導初期段階のヒト骨髄間葉系幹細胞は遊走および接着に関連する遺伝子発現プロファイルの変化を伴い、造血細胞の増殖促進を支持するSugino, Noriko 23 March 2016 (has links)
Final publication is available at http://www.sciencedirect.com/science/article/pii/S0006291X15310664 / 京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第19598号 / 医博第4105号 / 新制||医||1014(附属図書館) / 32634 / 京都大学大学院医学研究科医学専攻 / (主査)教授 三森 経世, 教授 開 祐司, 教授 妻木 範行 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM
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Nat1 promotes translation of specific proteins that induce differentiation of mouse embryonic stem cells / Nat1はマウス胚性幹細胞の分化を誘導する特定のタンパク質の翻訳を促進するSugiyama, Hayami 23 March 2017 (has links)
京都大学 / 0048 / 新制・課程博士 / 博士(医科学) / 甲第20286号 / 医科博第77号 / 新制||医科||5(附属図書館) / 京都大学大学院医学研究科医科学専攻 / (主査)教授 斎藤 通紀, 教授 篠原 隆司, 教授 戸口田 淳也 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM
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Derivation of ground-state female ES cells maintaining gamete-derived DNA methylation / 配偶子に由来するDNAメチル化を維持した高品質なES細胞の樹立Yagi, Masaki 26 March 2018 (has links)
京都大学 / 0048 / 新制・課程博士 / 博士(医科学) / 甲第21023号 / 医科博第84号 / 新制||医科||6(附属図書館) / 京都大学大学院医学研究科医科学専攻 / (主査)教授 斎藤 通紀, 教授 萩原 正敏, 教授 小川 誠司 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM
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Gene expression profile of Dclk1+ cells in intestinal tumors / 腸腫瘍におけるDclk1陽性細胞の遺伝子発現プロファイリングYamaga, Yuichi 23 January 2019 (has links)
京都大学 / 0048 / 新制・論文博士 / 博士(医学) / 乙第13221号 / 論医博第2168号 / 新制||医||1033(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 松田 道行, 教授 小川 誠司, 教授 武藤 学 / 学位規則第4条第2項該当 / Doctor of Medical Science / Kyoto University / DFAM
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Effect of Dimensionality on In Vitro Growth Environment and Mesenchymal Stem Cell FunctionZohora, Fatema Tuj 06 September 2018 (has links)
No description available.
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Mesenchymal Analysis of Human Pluripotent Stem Cell-Derived Gastrointestinal OrganoidsHaines, Lauren E. 04 November 2019 (has links)
No description available.
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Cell polarity in hematopoietic stem cell quiescence, signaling and fate determinationAlthoff, Mark J. 02 June 2020 (has links)
No description available.
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