A novel self-organizing embryonic stem cell system reveals signaling logic underlying the patterning of human ectoderm

Author:

Britton George1,Heemskerk Idse2,Hodge Rachel2,Qutub Amina A.3,Warmflash Aryeh23ORCID

Affiliation:

1. Systems Synthetic and Physical Biology Program, Rice University Houston, TX 77005, USA

2. Department of Biosciences, Rice University Houston, TX 77005, USA

3. Department of Bioengineering, Rice University Houston, TX 77005, USA

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 to study ectodermal patterning in humans. 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 which hESCs self-organize to form robust and quantitatively reproducible patterns corresponding to the complete medial-lateral axis of the embryonic ectoderm. 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. Thus, our platform is a powerful tool for studying human ectoderm patterning and for improving directed differentiation protocols.

Funder

National Institute of General Medical Sciences

National Science Foundation

Cancer Prevention and Research Institute of Texas

Simons Foundation

Publisher

The Company of Biologists

Subject

Developmental Biology,Molecular Biology

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