Nov 7, 2018

High-throughput micro-patterning platform reveals Nodal-dependent dissection of peri-gastrulation-associated versus pre-neurulation associated fate patterning

BioRxiv : the Preprint Server for Biology
Mukul TewaryPeter W Zandstra

Abstract

In vitro models of post-implantation human development are valuable to the fields of regenerative medicine, and developmental biology. Here, we report characterization of a robust in vitro platform that enabled high-throughput screening of multiple human pluripotent stem cell (hPSC) lines for their ability to undergo peri-gastrulation-like fate patterning upon BMP4 treatment of geometrically-confined colonies and observed significant variability. Further, we observed that when hPSCs were permitted to differentiate in conditions unsupportive of pluripotency, upregulation of endogenous Nodal correlated with expression of a gastrulation-associated gene profile, whereas Nodal downregulation correlated with a neurulation-associated gene profile expression. Given these observations, we hypothesized that inhibiting Nodal during a peri-gastrulation-like induction would induce fate patterning associated with the early stages of neurulation and observed experimental results consistent with this hypothesis. Mechanistically, we demonstrate a reaction-diffusion mediated self-organization of phosphorylated-SMAD1 signaling, and a positional-information mediated patterning of pre-neurulation-associated fates. Our work identifies a Nodal signal...Continue Reading

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Mentioned in this Paper

SMAD1 gene
Regenerative Medicine
Negative Regulation of Nodal Signaling Pathway
Pluripotent Stem Cells
Nodal Signaling Pathway
GARS gene
Bone morphogenetic protein 4
High Throughput Screening
Diffusion Weighted Imaging
Regulation of Gastrulation

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