The DOI matches its Crossref record; 47 of the 47 references it cites were found in a registry or an index.
Control of Human Embryonic Stem Cell Colony and Aggregate Size Heterogeneity Influences Differentiation Trajectories
Abstract
To better understand endogenous parameters that influence pluripotent cell differentiation we used human embryonic stem cells (hESCs) as a model system. We demonstrate that differentiation trajectories in aggregate (embryoid body [EB])-induced differentiation, a common approach to mimic some of the spatial and temporal aspects of in vivo development, are affected by three factors: input hESC composition, input hESC colony size, and EB size. Using a microcontact printing approach, size-specified hESC colonies were formed by plating single-cell suspensions onto micropatterned (MP) extracellular matrix islands. Subsequently, size-controlled EBs were formed by transferring entire colonies into suspension culture enabling the independent investigation of colony and aggregate size effects on differentiation induction. Gene and protein expression analysis of MP-hESC populations revealed that the ratio of Gata6 (endoderm-associated marker) to Pax6 (neural-associated marker) expression increased with decreasing colony size. Moreover, upon forming EBs from these MP-hESCs, we observed that differentiation trajectories were affected by both colony and EB size-influenced parameters. In MP-EBs generated from endoderm-biased (high Gata6/Pax6) input hESCs, higher mesoderm and cardiac induction was observed at larger EB sizes. Conversely, neural-biased (low Gata6/Pax6) input hESCs generated MP-EBs that exhibited higher cardiac induction in smaller EBs. Our analysis demonstrates that heterogeneity in hESC colony and aggregate size, typical in most differentiation strategies, produces subsets of appropriate conditions for differentiation into specific cell types. Moreover, our findings suggest that the local microenvironment modulates endogenous parameters that can be used to influence pluripotent cell differentiation trajectories. Disclosure of potential conflicts of interest is found at the end of this article.
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Takahashi, K., & Yamanaka, S. (2006) · Cell · doi:10.1016/j.cell.2006.07.024 · Cited by 26,673
Induction of Pluripotent Stem Cells from Adult Human Fibroblasts by Defined Factors
Takahashi, K., Tanabe, K., Ohnuki, M., Narita, M., Ichisaka, T., Tomoda, K., & Yamanaka, S. (2007) · Cell · doi:10.1016/j.cell.2007.11.019 · Cited by 20,221
Embryonic Stem Cell Lines Derived from Human Blastocysts
Thomson, J. A., Itskovitz-Eldor, J., Shapiro, S. S., Waknitz, M. A., Swiergiel, J. J., Marshall, V. S., & Jones, J. M. (1998) · Science · doi:10.1126/science.282.5391.1145 · Cited by 15,926
Induced Pluripotent Stem Cell Lines Derived from Human Somatic Cells
Yu, J., Vodyanik, M. A., Smuga-Otto, K., Antosiewicz-Bourget, J., Frane, J. L., Tian, S., Nie, J., Jonsdottir, G. A., Ruotti, V., Stewart, R., et al. (2007) · Science · doi:10.1126/science.1151526 · Cited by 10,310
Xia, Y., & Whitesides, G. M. (1998) · Angewandte Chemie International Edition · doi:10.1002/(sici)1521-3773(19980316)37:5<550::aid-anie550>3.0.co;2-g · Cited by 4,285
Embryonic stem cell lines from human blastocysts: somatic differentiation in vitro
Reubinoff, B. E., Pera, M. F., Fong, C.-Y., Trounson, A., & Bongso, A. (2000) · Nature Biotechnology · doi:10.1038/74447 · Cited by 2,706
Laflamme, M. A., Chen, K. Y., Naumova, A. V., Muskheli, V., Fugate, J. A., Dupras, S. K., Reinecke, H., Xu, C., Hassanipour, M., Police, S., et al. (2007) · Nature Biotechnology · doi:10.1038/nbt1327 · Cited by 2,206
Feeder-free growth of undifferentiated human embryonic stem cells
Xu, C., Inokuma, M. S., Denham, J., Golds, K., Kundu, P., Gold, J. D., & Carpenter, M. K. (2001) · Nature Biotechnology · doi:10.1038/nbt1001-971 · Cited by 1,870
Kehat, I., Kenyagin‐Karsenti, D., Snir, M., Segev, H., Amit, M., Gepstein, A., Livne, E., Binah, O., Itskovitz‐Eldor, J., & Gepstein, L. (2001) · Journal of Clinical Investigation · doi:10.1172/jci12131 · Cited by 1,814
Itskovitz-Eldor, J., Schuldiner, M., Karsenti, D., Eden, A., Yanuka, O., Amit, M., Soreq, H., & Benvenisty, N. (2000) · Molecular Medicine · doi:10.1007/bf03401776 · Cited by 1,500
Cited by
A method to recapitulate early embryonic spatial patterning in human embryonic stem cells
Warmflash, A., Sorre, B., Etoc, F., Siggia, E. D., & Brivanlou, A. H. (2014) · Nature Methods · doi:10.1038/nmeth.3016 · Cited by 885
Micropatterning as a tool to decipher cell morphogenesis and functions
Théry, M. (2010) · Journal of Cell Science · doi:10.1242/jcs.075150 · Cited by 730
Physical Cues of Biomaterials Guide Stem Cell Differentiation Fate
Higuchi, A., Ling, Q.-D., Chang, Y., Hsu, S.-T., & Umezawa, A. (2013) · Chemical Reviews · doi:10.1021/cr300426x · Cited by 458
Bioprinting for stem cell research
Tasoglu, S., & Demirci, U. (2013) · Trends in Biotechnology · doi:10.1016/j.tibtech.2012.10.005 · Cited by 422
Advances and challenges in stem cell culture
McKee, C., & Chaudhry, G. R. (2017) · Colloids and Surfaces B: Biointerfaces · doi:10.1016/j.colsurfb.2017.07.051 · Cited by 323
Metadata
- Authors
- Bauwens, C. L., Peerani, R., Niebruegge, S., Woodhouse, K. A., Kumacheva, E., Husain, M., & Zandstra, P. W.
- Venue
- Stem Cells
- Publisher
- Oxford University Press (OUP)
- Published
- 2008-06-26
- Volume
- 26
- Issue
- 9
- Pages
- 2300-2310
- ISSN
- 1066-5099 (ISSN-L)
- 1549-4918
- OpenAlex
- W2044193480
- Cited by
- 447
- References
- 47
- FWCI
- 10.17
- Type
- journal article
- Language
- en
- Open access
- closed
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- Bauwens, C. L., Peerani, R., Niebruegge, S., Woodhouse, K. A., Kumacheva, E., Husain, M., & Zandstra, P. W. (2008). Control of Human Embryonic Stem Cell Colony and Aggregate Size Heterogeneity Influences Differentiation Trajectories. Stem Cells. https://doi.org/10.1634/stemcells.2008-0183
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