A novel self-organizing embryonic stem cell system reveals signaling logic underlying the patterning of human ectoderm in two- and three-dimensions

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dc.contributor.advisorWarmflash, Aryehen_US
dc.creatorBritton, George Leslieen_US
dc.date.accessioned2020-08-11T21:49:39Zen_US
dc.date.available2021-02-01T06:01:11Zen_US
dc.date.created2020-08en_US
dc.date.issued2020-08-04en_US
dc.date.submittedAugust 2020en_US
dc.date.updated2020-08-11T21:49:39Zen_US
dc.description.abstractDuring development, the ectoderm is patterned by a combination of BMP and WNT signaling. Research in model organisms has provided substantial insight into this process; however, there are currently no systems in which to study ectodermal patterning in humans as it transitions from a two-dimensional to a three-dimensional tissue. Further, the complexity of neural plate border specification has made it difficult to transition from discovering the genes involved to deeper mechanistic understanding. Here, we develop an in vitro model of human ectodermal patterning in both two- and three-dimensions, in which human embryonic stem cells self-organize to form robust and quantitatively reproducible patterns corresponding to the complete medial-lateral axis of the embryonic ectoderm. Importantly, this organized tissue undergoes morphogenesis to form a close neural tube with an overlaying surface ectoderm, similar to what is found in vivo. Using this platform, we show that the duration of endogenous WNT signaling is a crucial control parameter, and that cells sense relative levels of BMP and WNT signaling in making fate decisions. These insights allowed us to develop an improved protocol for placodal differentiation in standard culture. Thus, our platform is a powerful tool for studying human ectoderm patterning and three-dimensional self-organization of neural structures that is otherwise impossible to study in utero.en_US
dc.embargo.terms2021-02-01en_US
dc.format.mimetypeapplication/pdfen_US
dc.identifier.citationBritton, George Leslie. "A novel self-organizing embryonic stem cell system reveals signaling logic underlying the patterning of human ectoderm in two- and three-dimensions." (2020) Diss., Rice University. <a href="https://hdl.handle.net/1911/109183">https://hdl.handle.net/1911/109183</a>.en_US
dc.identifier.urihttps://hdl.handle.net/1911/109183en_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.subjecthuman embryonic stem cellsen_US
dc.subjectmorphogenesisen_US
dc.subjectneural morphogenesisen_US
dc.subjecthuman ectoderm patterningen_US
dc.subjectneural cresten_US
dc.subjectplacodeen_US
dc.subjectneural plateen_US
dc.subjectepidermalen_US
dc.subjectpluripotenten_US
dc.subjectorganoiden_US
dc.subjectself-organizationen_US
dc.subjectBMP4en_US
dc.subjectWNTen_US
dc.titleA novel self-organizing embryonic stem cell system reveals signaling logic underlying the patterning of human ectoderm in two- and three-dimensionsen_US
dc.typeThesisen_US
dc.type.materialTexten_US
thesis.degree.departmentSystems, Synthetic and Physical Biologyen_US
thesis.degree.disciplineNatural Sciencesen_US
thesis.degree.grantorRice Universityen_US
thesis.degree.levelDoctoralen_US
thesis.degree.nameDoctor of Philosophyen_US
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