Engineering programmable material-to-cell pathways via synthetic notch receptors to spatially control differentiation in multicellular constructs.

Autor:	Garibyan M; Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA, USA.; Eli and Edythe Broad Center, University of Southern California, Los Angeles, CA, 90033, USA.; Alfred E. Mann Department of Biomedical Engineering, USC Viterbi School of Engineering, University of Southern California, Los Angeles, CA, USA., Hoffman T; Department of Bioengineering, University of California Los Angeles, Los Angeles, CA, USA., Makaske T; Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA, USA.; Eli and Edythe Broad Center, University of Southern California, Los Angeles, CA, 90033, USA.; Utrecht University in the lab of Prof. Dr. Lukas Kapitein, Los Angeles, CA, 90024, USA., Do SK; Alfred E. Mann Department of Biomedical Engineering, USC Viterbi School of Engineering, University of Southern California, Los Angeles, CA, USA., Wu Y; Department of Bioengineering, University of California Los Angeles, Los Angeles, CA, USA., Williams BA; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA., March AR; Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA, USA.; Eli and Edythe Broad Center, University of Southern California, Los Angeles, CA, 90033, USA., Cho N; Alfred E. Mann Department of Biomedical Engineering, USC Viterbi School of Engineering, University of Southern California, Los Angeles, CA, USA., Pedroncelli N; Department of Bioengineering, University of California Los Angeles, Los Angeles, CA, USA., Lima RE; Department of Bioengineering, University of California Los Angeles, Los Angeles, CA, USA., Soto J; Department of Bioengineering, University of California Los Angeles, Los Angeles, CA, USA., Jackson B; Department of Bioengineering, University of California Los Angeles, Los Angeles, CA, USA., Santoso JW; Alfred E. Mann Department of Biomedical Engineering, USC Viterbi School of Engineering, University of Southern California, Los Angeles, CA, USA., Khademhosseini A; Department of Bioengineering, University of California Los Angeles, Los Angeles, CA, USA.; Terasaki Institute for Biomedical Innovation (TIBI), Los Angeles, CA, 90024, USA., Thomson M; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA., Li S; Department of Bioengineering, University of California Los Angeles, Los Angeles, CA, USA.; Broad Stem Cell Center, University of California, Los Angeles, Los Angeles, CA, 90095, USA.; Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA, 90095, USA., McCain ML; Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA, USA. mlmccain@usc.edu.; Alfred E. Mann Department of Biomedical Engineering, USC Viterbi School of Engineering, University of Southern California, Los Angeles, CA, USA. mlmccain@usc.edu., Morsut L; Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA, USA. morsut@usc.edu.; Eli and Edythe Broad Center, University of Southern California, Los Angeles, CA, 90033, USA. morsut@usc.edu.; Alfred E. Mann Department of Biomedical Engineering, USC Viterbi School of Engineering, University of Southern California, Los Angeles, CA, USA. morsut@usc.edu.
Jazyk:	angličtina
Zdroj:	Nature communications [Nat Commun] 2024 Jul 13; Vol. 15 (1), pp. 5891. Date of Electronic Publication: 2024 Jul 13.
DOI:	10.1038/s41467-024-50126-1
Abstrakt:	Synthetic Notch (synNotch) receptors are genetically encoded, modular synthetic receptors that enable mammalian cells to detect environmental signals and respond by activating user-prescribed transcriptional programs. Although some materials have been modified to present synNotch ligands with coarse spatial control, applications in tissue engineering generally require extracellular matrix (ECM)-derived scaffolds and/or finer spatial positioning of multiple ligands. Thus, we develop here a suite of materials that activate synNotch receptors for generalizable engineering of material-to-cell signaling. We genetically and chemically fuse functional synNotch ligands to ECM proteins and ECM-derived materials. We also generate tissues with microscale precision over four distinct reporter phenotypes by culturing cells with two orthogonal synNotch programs on surfaces microcontact-printed with two synNotch ligands. Finally, we showcase applications in tissue engineering by co-transdifferentiating fibroblasts into skeletal muscle or endothelial cell precursors in user-defined micropatterns. These technologies provide avenues for spatially controlling cellular phenotypes in mammalian tissues. (© 2024. The Author(s).)
Databáze:	MEDLINE
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