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, Aryeh
dc.creatorBritton, George Leslie
dc.date.accessioned2020-08-11T21:49:39Z
dc.date.available2021-02-01T06:01:11Z
dc.date.created2020-08
dc.date.issued2020-08-04
dc.date.submittedAugust 2020
dc.date.updated2020-08-11T21:49:39Z
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.
dc.embargo.terms2021-02-01
dc.format.mimetypeapplication/pdf
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>.
dc.identifier.urihttps://hdl.handle.net/1911/109183
dc.language.isoeng
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.
dc.subjecthuman embryonic stem cells
dc.subjectmorphogenesis
dc.subjectneural morphogenesis
dc.subjecthuman ectoderm patterning
dc.subjectneural crest
dc.subjectplacode
dc.subjectneural plate
dc.subjectepidermal
dc.subjectpluripotent
dc.subjectorganoid
dc.subjectself-organization
dc.subjectBMP4
dc.subjectWNT.
dc.titleA novel self-organizing embryonic stem cell system reveals signaling logic underlying the patterning of human ectoderm in two- and three-dimensions
dc.typeThesis
dc.type.materialText
thesis.degree.departmentSystems, Synthetic and Physical Biology
thesis.degree.disciplineNatural Sciences
thesis.degree.grantorRice University
thesis.degree.levelDoctoral
thesis.degree.nameDoctor of Philosophy
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