Rac1 promotes the formation of heterotypic cell-in-cell structure / 生物工程学报

Heterotypic cell-in-cell structures (heCICs) are closely related to tumor development and progression, and have become a new frontier in life science research. Ras-related C3 botulinum toxin substrate 1 (Rac1) belongs to the classic Rho GTPase, which plays a key role in regulating the cytoskeleton and cell movement. To investigate the role and mechanism of Rac1 in the formation of heCICs, tumor cells and immune killer cells were labeled with cell-tracker, respectively, to establish the heCICs model. Upon treatment with the Rac1 inhibitor NSC23766, the formation of heCICs between tumor and immune cells was significantly reduced. The plasmid pQCXIP-Rac1-EGFP constructed by gene cloning was packaged into pseudoviruses that subsequently infect tumor cells to make cell lines stably expressing Rac1. As a result, the formation of heCICs was significantly increased upon Rac1 overexpression. These results demonstrated a promotive role of Rac1 in heCICs formation, which may facilitate treating cell-in-cell related diseases, such as tumors, by targeting Rac1.

Systemic analysis of tissue cells potentially vulnerable to SARS-CoV-2 infection by the protein-proofed single-cell RNA profiling of ACE2, TMPRSS2 and Furin proteases

Single-cell RNA profiling of ACE2, the SARS-CoV-2 receptor, had proposed multiple tissue cells as the potential targets of SARS-CoV-2, the novel coronavirus causing the COVID-19 pandemic. However, most were not echoed by the patients clinical manifestations, largely due to the lack of protein expression information of ACE2 and co-factors. Here, we incorporated the protein information to analyse the expression of ACE2, together with TMPRSS2 and Furin, two proteases assisting SARS-CoV-2 infection, at single cell level in situ, which we called protein-proofed single-cell RNA (pscRNA) profiling. Systemic analysis across 36 tissues revealed a rank list of candidate cells potentially vulnerable to SARS-CoV-2. The top targets are lung AT2 cells and macrophages, then cardiomyocytes and adrenal gland stromal cells, followed by stromal cells in testis, ovary and thyroid. Whereas, the polarized kidney proximal tubule cells, liver cholangiocytes and intestinal enterocytes are less likely to be the primary SARS-CoV-2 targets as ACE2 localizes at the apical region of cells, where the viruses may not readily reach. Actually, the stomach may constitute a physical barrier against SARS-CoV-2 as the acidic environment in normal stomach (pH < 2.0) could completely inactivate SARS-CoV-2 pseudo-viruses. These findings are in concert with the clinical characteristics of prominent lung symptoms, frequent heart injury, and uncommon intestinal symptoms and acute kidney injury. Together, we provide a comprehensive view on the potential SARS-CoV-2 targets by pscRNA profiling, and propose that, in addition to acute respiratory distress syndrome, attentions should also be paid to the potential injuries in cardiovascular, endocrine and reproductive systems during the treatment of COVID-19 patients.