Microwell-mediated control of embryoid body size regulates embryonic stem cell fate via differential expression of WNT5a and WNT11 Export

@article{citeulike:5919688, abstract = {10.1073/pnas.0905550106 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 \^{I}¼m in diameter), and in contrast, endothelial cell differentiation was increased in smaller EBs (150 \^{I}¼m 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.}, author = {Hwang, Yu-Shik and Chung, Bong G. and Ortmann, Daniel and Hattori, Nobuaki and Moeller, Hannes-Christian and Khademhosseini, Ali}, citeulike-article-id = {5919688}, citeulike-linkout-0 = {http://dx.doi.org/10.1073/pnas.0905550106}, citeulike-linkout-1 = {http://www.pnas.org/content/106/40/16978.abstract}, citeulike-linkout-2 = {http://www.pnas.org/content/106/40/16978.full.pdf}, citeulike-linkout-3 = {http://view.ncbi.nlm.nih.gov/pubmed/19805103}, citeulike-linkout-4 = {http://www.hubmed.org/display.cgi?uids=19805103}, day = {6}, doi = {10.1073/pnas.0905550106}, journal = {Proceedings of the National Academy of Sciences}, keywords = {stemcells}, month = {October}, number = {40}, pages = {16978--16983}, posted-at = {2009-10-10 17:22:28}, priority = {2}, title = {Microwell-mediated control of embryoid body size regulates embryonic stem cell fate via differential expression of WNT5a and WNT11}, url = {http://dx.doi.org/10.1073/pnas.0905550106}, volume = {106}, year = {2009} }

TY - JOUR ID - citeulike:5919688 L3 - citeulike-article-id:5919688 N2 - 10.1073/pnas.0905550106 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. IS - 40 JF - Proceedings of the National Academy of Sciences EP - 16983 TI - Microwell-mediated control of embryoid body size regulates embryonic stem cell fate via differential expression of WNT5a and WNT11 VL - 106 SP - 16978 KW - stemcells AU - Hwang, Yu-Shik AU - Chung, Bong AU - Ortmann, Daniel AU - Hattori, Nobuaki AU - Moeller, Hannes-Christian AU - Khademhosseini, Ali PY - 2009/10/06/ UR - http://dx.doi.org/10.1073/pnas.0905550106 ER -