Interrogating cellular fate decisions with high-throughput arrays of multiplexed cellular communities.
Interrogating cellular fate decisions with high-throughput arrays of multiplexed cellular communities.
复制标题
DOI：
10.1038/ncomms10309
复制
发表时间：
2016-01-12
影响因子：
16.6
通讯作者：
Schaffer DV
中科院分区：
文献类型：
--
作者：
Chen S;Bremer AW;Scheideler OJ;Na YS;Todhunter ME;Hsiao S;Bomdica PR;Maharbiz MM;Gartner ZJ;Schaffer DV
在体外重现异型细胞 - 细胞相互作用是剖析多种生物过程中细胞通讯作用的关键。这对于干细胞微环境尤其重要，在该环境中，邻近细胞提供指导性输入，支配细胞命运的决定。为了研究细胞 - 细胞信号网络的逻辑和动态，我们利用DNA编程的黏附作用制备了异型细胞 - 细胞相互作用阵列。我们的平台规定了每个阵列中多达四种不同细胞类型的数量和初始位置，并在长期培养过程中对细胞接触时间提供可调节的控制。在此，我们利用该平台研究单个成年神经干细胞在应对相互竞争的近分泌信号时细胞命运决定的动态。我们的结果表明，在Delta - like 1和ephrin - B2配体之间可能存在一种信号层级，因为当同时呈现这两种信号时，神经干细胞呈现出Delta - like 1的干细胞维持表型。
涉及多种细胞类型的体外实验无法控制细胞 - 细胞相互作用的化学计量或接触时间。在此，作者提出了一种基于印刷寡核苷酸的图案化共培养平台，该平台能够在单细胞水平上控制多达四种不同细胞类型的细胞 - 细胞相互作用。
Recreating heterotypic cell–cell interactions in vitro is key to dissecting the role of cellular communication during a variety of biological processes. This is especially relevant for stem cell niches, where neighbouring cells provide instructive inputs that govern cell fate decisions. To investigate the logic and dynamics of cell–cell signalling networks, we prepared heterotypic cell–cell interaction arrays using DNA-programmed adhesion. Our platform specifies the number and initial position of up to four distinct cell types within each array and offers tunable control over cell-contact time during long-term culture. Here, we use the platform to study the dynamics of single adult neural stem cell fate decisions in response to competing juxtacrine signals. Our results suggest a potential signalling hierarchy between Delta-like 1 and ephrin-B2 ligands, as neural stem cells adopt the Delta-like 1 phenotype of stem cell maintenance on simultaneous presentation of both signals. In vitro assays involving multiple cell types cannot control the stoichiometry or contact times of cell-cell interactions. Here, the authors present a patterned co-culture platform based on printed oligonucleotides capable of controlling cell-cell interactions of up to four different cell types at the single-cell level.