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Nat Methods. 2015 Oct;12(10):975-81. doi: 10.1038/nmeth.3553. Epub 2015 Aug 31.

Programmed synthesis of three-dimensional tissues.

Author information

1
Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, California, USA.
2
Tetrad Graduate Program, University of California, San Francisco, San Francisco, California, USA.
3
Chemistry &Chemical Biology Graduate Program, University of California, San Francisco, San Francisco, California, USA.
4
Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, California, USA.
5
Graduate Program in Bioengineering, University of California, Berkeley, and University of California, San Francisco, Berkeley, California, USA.
6
Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California, USA.
7
Center for Systems and Synthetic Biology, University of California, San Francisco, San Francisco, California, USA.

Abstract

Reconstituting tissues from their cellular building blocks facilitates the modeling of morphogenesis, homeostasis and disease in vitro. Here we describe DNA-programmed assembly of cells (DPAC), a method to reconstitute the multicellular organization of organoid-like tissues having programmed size, shape, composition and spatial heterogeneity. DPAC uses dissociated cells that are chemically functionalized with degradable oligonucleotide 'Velcro', allowing rapid, specific and reversible cell adhesion to other surfaces coated with complementary DNA sequences. DNA-patterned substrates function as removable and adhesive templates, and layer-by-layer DNA-programmed assembly builds arrays of tissues into the third dimension above the template. DNase releases completed arrays of organoid-like microtissues from the template concomitant with full embedding in a variety of extracellular matrix (ECM) gels. DPAC positions subpopulations of cells with single-cell spatial resolution and generates cultures several centimeters long. We used DPAC to explore the impact of ECM composition, heterotypic cell-cell interactions and patterns of signaling heterogeneity on collective cell behaviors.

PMID:
26322836
PMCID:
PMC4589502
DOI:
10.1038/nmeth.3553
[Indexed for MEDLINE]
Free PMC Article
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