title: Programmed synthesis of three-dimensional tissues.
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.
authors: Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, California, USA.|Tetrad Graduate Program, University of California, San Francisco, San Francisco, California, USA.
authors: Michael E
authors: ME
authors: Todhunter
authors: Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, California, USA.|Chemistry &Chemical Biology Graduate Program, University of California, San Francisco, San Francisco, California, USA.
authors: Noel Y
authors: http://orcid.org/0000-0002-7145-7425
authors: NY
authors: Jee
authors: Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, California, USA.
authors: Alex J
authors: http://orcid.org/0000-0001-6801-3455
authors: AJ
authors: Hughes
authors: Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, California, USA.
authors: Maxwell C
authors: MC
authors: Coyle
authors: Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, California, USA.|Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, California, USA.|Graduate Program in Bioengineering, University of California, Berkeley, and University of California, San Francisco, Berkeley, California, USA.
authors: Alec
authors: A
authors: Cerchiari
authors: Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, California, USA.|Tetrad Graduate Program, University of California, San Francisco, San Francisco, California, USA.
authors: Justin
authors: J
authors: Farlow
authors: Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, California, USA.|Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California, USA.
authors: James C
authors: JC
authors: Garbe
authors: Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California, USA.
authors: Mark A
authors: MA
authors: LaBarge
authors: Chemistry &Chemical Biology Graduate Program, University of California, San Francisco, San Francisco, California, USA.|Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, California, USA.|Graduate Program in Bioengineering, University of California, Berkeley, and University of California, San Francisco, Berkeley, California, USA.
authors: Tejal A
authors: TA
authors: Desai
authors: Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, California, USA.|Tetrad Graduate Program, University of California, San Francisco, San Francisco, California, USA.|Chemistry &Chemical Biology Graduate Program, University of California, San Francisco, San Francisco, California, USA.|Graduate Program in Bioengineering, University of California, Berkeley, and University of California, San Francisco, Berkeley, California, USA.|Center for Systems and Synthetic Biology, University of California, San Francisco, San Francisco, California, USA.
authors: Zev J
authors: ZJ
authors: Gartner
mesh_terms: D002448:Cell Adhesion; D002450:Cell Communication; D004247:DNA / Q000737:chemistry*; D003851:Deoxyribonucleases / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology; D005109:Extracellular Matrix / Q000737:chemistry* / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007091:Image Processing, Computer-Assisted; D009841:Oligonucleotides / Q000737:chemistry; D009940:Organoids / Q000166:cytology / Q000502:physiology; D017154:Stromal Cells / Q000166:cytology; D023822:Tissue Engineering / Q000379:methods*
chemical_list: D009841:Oligonucleotides; D004247:DNA; D003851:Deoxyribonucleases