Understanding Receptor-Mediated NK Cell Adhesion and Motility Throughout development

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dc.contributor.advisorDiehl, Michaelen_US
dc.contributor.advisorMace, Emilyen_US
dc.creatorLee, Barclayen_US
dc.date.accessioned2019-12-06T19:42:02Zen_US
dc.date.available2019-12-06T19:42:02Zen_US
dc.date.created2019-12en_US
dc.date.issued2019-12-05en_US
dc.date.submittedDecember 2019en_US
dc.date.updated2019-12-06T19:42:03Zen_US
dc.description.abstractHuman natural killer cells originate from hematopoietic stem cells and can be differentiated in vitro through coculture with EL08.1D2 cells, a developmentally supportive stromal cell line. It is thought that these stroma support NK cell maturation by providing signaling cues and structural support that the stem cell would normally experience within tissue in vivo. These cues from the local microenvironment induce changes in cell motility and adhesion to guide cell fate. Although these signals are well studied in T and B lymphocytes, the full extent of these interactions is currently not well understood for NK cell development. In this dissertation, I describe changes in NK cell motility and adhesion that occur throughout development. Specifically, I show that developing NK cells undergo continuous changes in cell migration velocity and displacement that define their differentiation from precursor to functionally mature cell. In addition, I present extracellular matrix (ECM) derived from EL08.1D2 stroma as an alternate substrate for supporting NK cell development. This cell-derived matrix is composed of naturally secreted ECM components from the stroma and contains expected ECM components such as collagen and fibronectin. I show that this cell-derived matrix can support NK cell differentiation from hematopoietic precursor cells, and I further define the migratory and adhesive behaviors of NK developmental intermediates on EL08.1D2 and EL08.1D2-derived cell free matrix. Particularly, NK cell motility is acquired through development and NK cells undergo similar motility on both EL08.1D2 stroma and cell-derived matrix. The information presented in this work defines the extent to which developmentally supportive stroma are required for NK cell development in vitro and provides an avenue into research for alternative substrates and conditions for NK cell development.en_US
dc.format.mimetypeapplication/pdfen_US
dc.identifier.citationLee, Barclay. "Understanding Receptor-Mediated NK Cell Adhesion and Motility Throughout development." (2019) Diss., Rice University. <a href="https://hdl.handle.net/1911/107803">https://hdl.handle.net/1911/107803</a>.en_US
dc.identifier.urihttps://hdl.handle.net/1911/107803en_US
dc.language.isoengen_US
dc.rightsCopyright is held by the author, unless otherwise indicated. Permission to reuse, publish, or reproduce the work beyond the bounds of fair use or other exemptions to copyright law must be obtained from the copyright holder.en_US
dc.subjectNK cellen_US
dc.subjectmotilityen_US
dc.subjectcell-derived matrixen_US
dc.subjectdevelopmenten_US
dc.subjecthematopoietic stem cellen_US
dc.subjectimmunologyen_US
dc.subjectlymphocyteen_US
dc.titleUnderstanding Receptor-Mediated NK Cell Adhesion and Motility Throughout developmenten_US
dc.typeThesisen_US
dc.type.materialTexten_US
thesis.degree.departmentBioengineeringen_US
thesis.degree.disciplineEngineeringen_US
thesis.degree.grantorRice Universityen_US
thesis.degree.levelDoctoralen_US
thesis.degree.majorNK cell biologyen_US
thesis.degree.nameDoctor of Philosophyen_US
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