Engel Leeya, Liu Kevin J, Cui Kiara W, de la Serna Eva L, Vachharajani Vipul T, Dundes Carolyn E, Zheng Sherry Li, Begur Manali, Loh Kyle M, Ang Lay Teng, Dunn Alexander R
Department of Chemical Engineering, Stanford University, Stanford, CA 94305, USA.
Faculty of Mechanical Engineering, Technion - Israel Institute of Technology, Haifa 3200003, Israel.
iScience. 2025 Jan 4;28(3):111744. doi: 10.1016/j.isci.2025.111744. eCollection 2025 Mar 21.
Understanding how morphogen gradients spatially pattern tissues is a fundamental question in developmental biology but can be difficult to directly address using conventional approaches. Here, we expose hPSC-derived endoderm cells to countervailing gradients of anteriorizing and posteriorizing signals using a widely available microfluidic device. This approach yielded spatially patterned cultures comprising anterior foregut (precursor to the thyroid, esophagus, and lungs) and mid/hindgut (precursor to the intestines) cells, whose identities were confirmed using single-cell RNA sequencing (scRNA-seq). By exposing stem cells to externally applied signaling gradients, this widely accessible microfluidic platform should accelerate the production of spatially patterned tissues, complementing internally self-organizing organoids. Applying artificial morphogen gradients may also illuminate how developing tissues interpret signaling gradients in systems that are not readily accessible for studies
理解形态发生素梯度如何在空间上构建组织模式是发育生物学中的一个基本问题，但使用传统方法可能难以直接解决。在这里，我们使用一种广泛可用的微流控装置，将人多能干细胞衍生的内胚层细胞暴露于前后化信号的相反梯度中。这种方法产生了包含前肠（甲状腺、食道和肺的前体）和中/后肠（肠道的前体）细胞的空间模式化培养物，其身份通过单细胞RNA测序（scRNA-seq）得到证实。通过将干细胞暴露于外部施加的信号梯度，这个广泛可用的微流控平台应该会加速空间模式化组织的产生，补充内部自组织类器官。应用人工形态发生素梯度也可能阐明发育中的组织如何在难以进行研究的系统中解读信号梯度。
