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dc.contributor.advisor Warmflash, Aryeh
dc.creatorBritton, George Leslie
dc.date.accessioned 2020-08-11T21:49:39Z
dc.date.available 2021-02-01T06:01:11Z
dc.date.created 2020-08
dc.date.issued 2020-08-04
dc.date.submitted August 2020
dc.identifier.citation Britton, 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. https://hdl.handle.net/1911/109183.
dc.identifier.urihttps://hdl.handle.net/1911/109183
dc.description.abstract During 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.format.mimetype application/pdf
dc.language.iso eng
dc.subjecthuman embryonic stem cells
morphogenesis
neural morphogenesis
human ectoderm patterning
neural crest
placode
neural plate
epidermal
pluripotent
organoid
self-organization
BMP4
WNT.
dc.title A novel self-organizing embryonic stem cell system reveals signaling logic underlying the patterning of human ectoderm in two- and three-dimensions
dc.type Thesis
dc.date.updated 2020-08-11T21:49:39Z
dc.type.material Text
thesis.degree.department Systems, Synthetic and Physical Biology
thesis.degree.discipline Natural Sciences
thesis.degree.grantor Rice University
thesis.degree.level Doctoral
thesis.degree.name Doctor of Philosophy
dc.embargo.terms 2021-02-01


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