Udani Shreya, Langerman Justin, Koo Doyeon, Baghdasarian Sevana, Cheng Brian, Kang Simran, Soemardy Citradewi, de Rutte Joseph, Plath Kathrin, Carlo Dino Di
Department of Bioengineering, University of California - Los Angeles, Los Angeles, CA 90095, USA.
Department of Biological Chemistry, David Geffen School of Medicine, University of California - Los Angeles, Los Angeles, CA 90095, USA.
bioRxiv. 2023 Jan 8:2023.01.07.523110. doi: 10.1101/2023.01.07.523110.
Cells secrete numerous bioactive molecules essential for the function of healthy organisms. However, there are no scalable methods to link individual cell secretions to their transcriptional state. By developing and using secretion encoded single-cell sequencing (SEC-seq), which exploits hydrogel nanovials to capture individual cells and their secretions, we simultaneously measured the secretion of vascular endothelial growth factor A (VEGF-A) and the transcriptome for thousands of individual mesenchymal stromal cells (MSCs). We found that VEGF-A secretion is heterogeneous across the cell population and lowly correlated with the transcript level. While there is a modest population-wide increase in VEGF-A secretion by hypoxic induction, highest VEGF-A secretion across normoxic and hypoxic culture conditions occurs in a subpopulation of MSCs characterized by a unique gene expression signature. Taken together, SEC-seq enables the identification of specific genes involved in the control of secretory states, which may be exploited for developing means to modulate cellular secretion for disease treatment.
细胞分泌许多对健康生物体功能至关重要的生物活性分子。然而，目前尚无可扩展的方法将单个细胞的分泌物与其转录状态联系起来。通过开发和使用分泌编码单细胞测序（SEC-seq），该技术利用水凝胶纳米小瓶捕获单个细胞及其分泌物，我们同时测量了数千个单个间充质基质细胞（MSC）的血管内皮生长因子A（VEGF-A）分泌和转录组。我们发现，VEGF-A分泌在细胞群体中是异质的，并且与转录水平的相关性较低。虽然低氧诱导使VEGF-A分泌在全群体中有适度增加，但在常氧和低氧培养条件下，VEGF-A分泌最高的情况出现在具有独特基因表达特征的MSC亚群中。综上所述，SEC-seq能够识别参与控制分泌状态的特定基因，这可能有助于开发调节细胞分泌以治疗疾病的方法。
