Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94158, USA.
Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94158, USA; Graduate Program in Bioengineering, University of California, San Francisco and University of California, Berkeley, San Francisco, CA 94158, USA.
Dev Cell. 2021 Feb 8;56(3):356-365.e9. doi: 10.1016/j.devcel.2020.12.020. Epub 2021 Jan 22.
Renewing tissues have the remarkable ability to continually produce both proliferative progenitor and specialized differentiated cell types. How are complex milieus of microenvironmental signals interpreted to coordinate tissue-cell-type composition? Here, we investigate the responses of intestinal epithelium to individual and paired perturbations across eight epithelial signaling pathways. Using a high-throughput approach that combines enteroid monolayers and quantitative imaging, we identified conditions that enrich for specific cell types as well as interactions between pathways. Importantly, we found that modulation of transit-amplifying cell proliferation changes the ratio of differentiated secretory to absorptive cell types. These observations highlight an underappreciated role for transit-amplifying cells in the tuning of differentiated cell-type composition.
更新组织具有显著的能力，可以持续产生增殖祖细胞和专门的分化细胞类型。复杂的微环境信号如何被解释以协调组织-细胞类型组成？在这里，我们研究了肠上皮细胞对八种上皮信号通路中单个和成对扰动的反应。我们使用一种结合类器官单层和定量成像的高通量方法，确定了特定细胞类型富集的条件以及途径之间的相互作用。重要的是，我们发现过渡扩增细胞增殖的调节改变了分化分泌细胞与吸收细胞类型的比例。这些观察结果突出了过渡扩增细胞在调节分化细胞类型组成方面的作用。
