Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, Massachusetts 02115, United States.
Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, United States.
ACS Synth Biol. 2024 Sep 20;13(9):2753-2763. doi: 10.1021/acssynbio.4c00037. Epub 2024 Aug 28.
Multicellular organisms originate from a single cell, ultimately giving rise to mature organisms of heterogeneous cell type composition in complex structures. Recent work in the areas of stem cell biology and tissue engineering has laid major groundwork in the ability to convert certain types of cells into other types, but there has been limited progress in the ability to control the morphology of cellular masses as they grow. Contemporary approaches to this problem have included the use of artificial scaffolds, 3D bioprinting, and complex media formulations; however, there are no existing approaches to controlling this process purely through genetics and from a single-cell starting point. Here we describe a computer-aided design approach, called , for designing recombinase-based genetic circuits for controlling the formation of multicellular masses into arbitrary shapes in human cells.
多细胞生物起源于单个细胞,最终在复杂结构中形成具有异质细胞类型组成的成熟生物体。最近在干细胞生物学和组织工程领域的工作为将某些类型的细胞转化为其他类型的细胞奠定了重要基础,但在控制细胞团生长时的形态方面进展有限。目前解决这个问题的方法包括使用人工支架、3D 生物打印和复杂的培养基配方;然而,目前还没有通过遗传学和单细胞起始点来控制这个过程的方法。在这里,我们描述了一种计算机辅助设计方法,称为,用于设计基于重组酶的遗传电路,以控制人类细胞中多细胞团形成任意形状。