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TANG, Y.

Publications and source records attributed to TANG, Y..

2 recordsLinked to original sources

Circulating Microparticles: Optimization and Standardization of Isolation Protocols and Reassessment of Their Characteristics and Functions

Microparticles (MPs) are convenient for clinical diagnosis, and have functional roles in signal transduction. Although the importance of MPs is being increasingly recognized, the diversity of isolated protocols for MPs results in a heterogeneous population of their unknown origins, even expands to uncertain functions. Here we systematically studied the composition of MPs at different centrifugal speed intervals, and found that 3000g was a critical centrifugation speed in determining new MPs composition. The platelet-derived particles accounted for more than 80% under 3000g, while only about 20% in MPs obtained over 3000g. Furthermore, we found that the function of new MPs was significantly different from that of traditional ones, such as procoagulation activity, anti-inflammation and clinical diagnosis etc. Thus, our work optimized the method of MPs isolation, clarified some characteristics and physiological functions that should belong to platelets rather than MPs, which will derive new conceptual MPs for its composition and function.

cell biology↗

ZEB1 controls a lineage-specific transcriptional program essential for melanoma cell state transitions

Cell plasticity sustains intra-tumor heterogeneity and treatment resistance in melanoma. Deciphering the transcriptional mechanisms governing reversible phenotypic transitions between proliferative/differentiated and invasive/stem-like states is required. Expression of the ZEB1 transcription factor is frequently activated in melanoma, where it fosters adaptive resistance to targeted therapies. Here, we performed a genome-wide characterization of ZEB1 transcriptional targets, by combining ChIP-sequencing and RNA-sequencing, upon phenotype switching in melanoma models. We identified and validated ZEB1 binding peaks in the promoter of key lineage-specific genes crucial for melanoma cell identity. Mechanistically, ZEB1 negatively regulates SOX10-MITF dependent proliferative/melanocytic programs and positively regulates AP-1 driven invasive and stem-like programs. Comparative analyses with breast carcinoma cells revealed lineage-specific ZEB1 binding, leading to the design of a more reliable melanoma-specific ZEB1 regulon. We then developed single-cell spatial multiplexed analyses to characterize melanoma cell states intra-tumoral heterogeneity in human melanoma samples. Combined with scRNA-Seq analyses, our findings confirmed increased ZEB1 expression in Neural-Crest-like cells and mesenchymal cells, underscoring its significance in vivo in both populations. Overall, our results define ZEB1 as a major transcriptional regulator of cell states transitions and provide a better understanding of lineage-specific transcriptional programs sustaining intra-tumor heterogeneity in melanoma. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=170 SRC="FIGDIR/small/526467v2_ufig1.gif" ALT="Figure 1"> View larger version (28K): org.highwire.dtl.DTLVardef@6c487eorg.highwire.dtl.DTLVardef@10b52aborg.highwire.dtl.DTLVardef@60821eorg.highwire.dtl.DTLVardef@1fe9f90_HPS_FORMAT_FIGEXP M_FIG C_FIG

cancer biology↗