한빛사논문, 상위피인용논문
- 조회6,603
Abstract
aCenter for Biomedical Engineering, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA 02139;
bHarvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139; and
cDepartment of Bionano Engineering, Hanyang University, Ansan, 426-791, South Korea
2Present address: Department of Oral Biology and Institute of Oral Biology, School of Dentistry, Kyung Hee University, Seoul 130-701, South Korea.
3Present address: Department of Internal Medicine II, Cardiology, University of Ulm, Ulm, Germany; and Department of Surgery and Laboratory for Regenerative Medicine, West Forvie Building, Robinson Way, University of Cambridge, CB2 0SZ, United Kingdom.
4Present address: Department of Periodontology, School of Dentistry, Aichi-Gakuin University, 2-11 Suemori-dori, Chikusa-ku, Nagoya 464-8651, Japan.
5Present address: École Supérieure de Biotechnologie de Strasbourg, F-67412 Illkirch-Cedex, France.
1Y.-S.H, B.G.C., and D.O. contributed equally to this work.
Edited by Robert Langer, Massachusetts Institute of Technology, Cambridge, MA, and approved July 31, 2009 (received for review May 20, 2009)
Abstract
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.hydrogel microwells, stem cell differentiation, WNT signal pathway
Footnotes
6To whom correspondence should be addressed at: Partners Research Building, 65 Landsdowne Street, Room 265, Cambridge, MA, 02139.
Author contributions: Y.-S.H., B.G.C., and A.K. designed research; Y.-S.H., B.G.C., D.O., N.H., and H.-C.M. performed research; Y.-S.H., B.G.C., D.O., N.H., and H.-C.M. analyzed data; and Y.-S.H., B.G.C., and A.K. wrote the paper.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission.
논문정보
- Research article
- 2009년 09월 (BRIC 등록일 )
- 국내+국외 연구진
- 바이오·의료융합 > 바이오센싱 및 나노바이오물질
- 60회 이상 인용된 논문 (상위피인용논문 등록일 2012-06-19)
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