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Biology subjects

Qing, Q.

Publications and source records attributed to Qing, Q..

4 recordsLinked to original sources

Electrostatic modulation of signaling at cell membrane: Waveform- and time-dependent electric control of ERK dynamics

Different exogenous electric fields (EF) can guide cell migration, disrupt proliferation, and program cell development. Studies have shown that many of these processes were initiated at the cell membrane, but the mechanism has been unclear, especially for conventionally non-excitable cells. In this study, we focus on the electrostatic aspects of EF coupling with the cell membrane by eliminating Faradaic processes with dielectric-coated microelectrodes, and show that the ERK signaling pathway of epithelial cells (MCF10A) can be both inhibited and activated by AC EF with different amplitude thresholds, peaking times and refractory periods. Interestingly, the ERK responses were sensitive to the waveform and timing of EF stimulation pulses, depicting the characteristics of electrostatic and dissipative interactions. Blocker tests and correlated changes of active Ras on the cell membrane with ERK signals indicated that both EGFR and Ras were involved in the rich ERK dynamics induced by EF. We propose that the frequency-dependent dielectric relaxation process could be an important mechanism to couple EF energy to the cell membrane region and modulate membrane protein-initiated signaling pathways, which can be further explored to precisely control cell behavior and fate with high temporal and spatial resolution.

biophysics↗

MIIP downregulation promotes colorectal cancer progression via inducing adjacent adipocytes browning

The enrichment of peri-cancerous adipocytes is one of the distinctive features of colorectal cancer (CRC), which accelerates the disease progression and worsens the prognosis. The communication between tumor cells and adjacent adipocytes plays an important role in this process. However, the detailed mechanisms remain largely unknown. Here we demonstrated MIIP is downregulated in high-grade CRC, and revealed its role and mechanism in tumor cell-adipocyte communication. By detecting MIIP expression in CRC tissues and adjacent normal tissues, we found MIIP was significantly decreased in CRC, and was closely related to adjacent adipocytes browning. In detail, MIIP reduction altered the N-linked glycosylation modification of AZGP1 and thus alleviated the inhibition of secretion. AZGP1, a critical lipid mobilization factor, led to the intensification of adipocytes browning and the release of free fatty acids (FFAs), which in turn fueled for CRC progression. Our data demonstrate that MIIP plays a key regulatory role in the communication between CRC and neighboring adipocytes by mediating AZGP1 secretion, and MIIP reduction leads to adipose browning-induced cancer rapid progression and poor prognosis.

cancer biology↗

Nanotopography modulates intracellular excitable systems through cytoskeleton actuation

Cellular sensing of most environmental cues involves receptors that affect a signal-transduction excitable network (STEN), which is coupled to a cytoskeletal excitable network (CEN). We show that the mechanism of sensing of nanoridges is fundamentally different. CEN activity occurs preferentially on nanoridges, whereas STEN activity is constrained between nanoridges. In the absence of STEN, waves disappear, but long-lasting F-actin puncta persist along the ridges. When CEN is suppressed, wave propagation is no longer constrained by nanoridges. A computational model reproduces these experimental observations. Our findings indicate that nanotopography is sensed directly by CEN, whereas STEN is only indirectly affected due to a CEN-STEN feedback loop. These results explain why texture sensing is robust, and acts cooperatively with multiple other guidance cues in complex microenvironments. One-Sentence SummaryCells sense nanotopography directly through their cytoskeletal dynamics, in a reversal of traditional signaling pathway hierarchies.

biophysics↗

Transcriptome Landscape of Human Oocytes and Granulosa Cells Throughout Folliculogenesis

Folliculogenesis is a highly regulated process that involves bidirectional interactions of the oocytes and surrounding granulosa cells (GCs). Little is unknown, however, about the transcriptomic profiles of human oocytes and GCs throughout folliculogenesis. Here we performed a high resolution RNA-Seq of human oocytes and GCs at each follicular stage, which revealed unique transcriptional profiles, stage-specific signature genes, oocyte- and GC-derived genes that reflect ovarian reserve. We identified reciprocal cell-to-cell interactions between oocytes and GCs, including NOTCH, TGF-{beta} signaling and gap junctions and determined the expression patterns of maternal-effect genes involved in folliculogenesis and early embryogenesis. Finally, we demonstrated robust differences between human and mice oocyte transcriptomes. This is the first comprehensive overview of the transcriptomic signatures governing the stepwise human folliculogenesis in-vivo that provides a valuable resource for basic and translational research in human reproductive biology.

cell biology↗