Microwell-mediated Control of Embryoid Body Size Regulates Embryonic Stem Cell Fate Via Differential Expression of WNT5a and WNT11

Recently, various approaches for controlling the embryonic stem (ES) cell microenvironment have been developed for regulating cellular fate decisions. It has been reported that the lineage specific differentiation could be affected by the size of ES cell colonies and embryoid bodies (EBs). However,...

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Main Authors: Khademhosseini, Ali (Contributor), Hwang, Yu-Shik (Contributor), Chung, Bong Geun (Contributor), Moeller, Hannes-Christian (Contributor), Ortmann, Daniel (Contributor), Hattori, Nobuaki (Contributor)
Other Authors: Harvard University- (Contributor)
Format: Article
Language:English
Published: National Academy of Sciences (U.S.), 2010-09-03T14:37:19Z.
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Online Access:Get fulltext
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100 1 0 |a Khademhosseini, Ali  |e author 
100 1 0 |a Harvard University-  |e contributor 
100 1 0 |a Khademhosseini, Ali  |e contributor 
100 1 0 |a Khademhosseini, Ali  |e contributor 
100 1 0 |a Hwang, Yu-Shik  |e contributor 
100 1 0 |a Chung, Bong Geun  |e contributor 
100 1 0 |a Moeller, Hannes-Christian  |e contributor 
100 1 0 |a Ortmann, Daniel  |e contributor 
100 1 0 |a Hattori, Nobuaki  |e contributor 
700 1 0 |a Hwang, Yu-Shik  |e author 
700 1 0 |a Chung, Bong Geun  |e author 
700 1 0 |a Moeller, Hannes-Christian  |e author 
700 1 0 |a Ortmann, Daniel  |e author 
700 1 0 |a Hattori, Nobuaki  |e author 
245 0 0 |a Microwell-mediated Control of Embryoid Body Size Regulates Embryonic Stem Cell Fate Via Differential Expression of WNT5a and WNT11 
260 |b National Academy of Sciences (U.S.),   |c 2010-09-03T14:37:19Z. 
856 |z Get fulltext  |u http://hdl.handle.net/1721.1/58302 
520 |a Recently, various approaches for controlling the embryonic stem (ES) cell microenvironment have been developed for regulating cellular fate decisions. It has been reported that the lineage specific differentiation could be affected by the size of ES cell colonies and embryoid bodies (EBs). However, much of the underlying biology has not been well elucidated. In this study, we used microengineered hydrogel microwells to direct ES cell differentiation and determined the role of WNT signaling pathway in directing the differentiation. This was accomplished by forming ES cell aggregates within microwells to form different size EBs. We determined that cardiogenesis was enhanced in larger EBs (450 μm in diameter), and in contrast, endothelial cell differentiation was increased in smaller EBs (150 μm in diameter). Furthermore, we demonstrated that the EB-size mediated differentiation was driven by differential expression of WNTs, particularly noncanonical WNT pathway, according to EB size. The higher expression of WNT5a in smaller EBs enhanced endothelial cell differentiation. In contrast, the increased expression of WNT11 enhanced cardiogenesis. This was further validated by WNT5a-siRNA transfection assay and the addition of recombinant WNT5a. Our data suggest that EB size could be an important parameter in ES cell fate specification via differential gene expression of members of the noncanonical WNT pathway. Given the size-dependent response of EBs to differentiate to endothelial and cardiac lineages, hydrogel microwell arrays could be useful for directing stem cell fates and studying ES cell differentiation in a controlled manner. 
520 |a National Institutes of Health (U.S.) (DE019024, HL092836, and EB007249) 
546 |a en_US 
690 |a Hydrogel microwells 
690 |a Stem cell differentiation 
690 |a WNT signal pathway 
655 7 |a Article 
773 |t Proceedings of the National Academy of Sciences of the United States of America