Biology subjects

Lv, C.

Publications and source records attributed to Lv, C..

22 records · Page 2Linked to original sources

bioRxiv2019

Stromal ISLR promotes intestinal regeneration and cancer by suppressing epithelial Hippo signaling

The YAP signaling activation in epithelial cells is essential for intestinal regeneration and tumorigenesis. However, the molecular mechanism linking stromal signals to YAP-mediated intestinal regeneration and tumorigenesis is poorly defined. Here we report a stroma-epithelia YAP signaling axis essential for stromal cells to modulate epithelial cell growth during intestinal regeneration and tumorigenesis. Specifically, upon inflammation and in cancer, an oncogenic transcription factor ETS1 in stromal cells induces expression of a secreted protein ISLR that can directly binds to a transmembrane protocadherin FAT1 on the surface of epithelial cells. This binding suppressed the Hippo signaling by disrupting MST1-FAT1 association, resulting in YAP signaling activation. Deletion of Islr in stromal cells in mice markedly impaired intestinal regeneration, and suppressed tumorigenesis in the colon. Moreover, the expression of stromal cell-specific ISLR and ETS1 significantly increased in inflamed mucosa of human IBD patients and in human colorectal adenocarcinoma, accounting for the epithelial YAP hyperactivation. Collectively, our findings uncovered a molecular mechanism governing signals for communication between stroma and epithelium during tissue regeneration and tumorigenesis.

cancer biology↗

bioRxiv2019

Ginsenoside Rg1 defenses PC-12 cells against hydrogen peroxide-caused damage via up-regulation of miR-216a-5p

BackgroundSpinal cord injury (SCI) is a destructive trauma accompanying with local injury, half of which cause chronic paralysis. Ginsenoside Rg1 exerts anti-apoptosis and anti-autophagy properties. Therefore, our goal was to study the protective mechanism of Rg1 in attenuating cell injury.\n\nMethodsMiR-216a-5p inhibitor was transfected into PC-12 cells, then cells were pre-treated by Rg1 and treated with 300 M hydrogen peroxide (H2O2) for 24 h. CCK-8 and apoptosis experiments were done to test cell activity and apoptosis respectively. Expression of miR-216a-5p and cell damage relative factors was tested via qRT-PCR and western blot experiments, respectively.\n\nResultsH2O2 induced cell activity suppression, apoptosis and autophagy well at the concentration of 300 M, leading cell injury. Rg1 could attenuate cell injury induced by H2O2 at the working concentration of 200 M that it elevated cell activity, attenuated apoptosis and autophagy and activated PI3K/AKT and AMPK signal pathways. Further, miR-216a-5p was up-regulated by Rg1. Rg1 played its role in relieving cell injury by positively regulating miR-216a-5p.\n\nConclusionOur study demonstrated that Rg1 attenuated H2O2-caused cell injury through positively regulated miR-216a-5p.

biochemistry↗

bioRxiv2019

T Lymphopoiesis from Pluripotent Stem Cells by Defined Transcription Factors at Single Cell Resolution

Achievement of immunocompetent and therapeutic T lymphopoiesis from pluripotent stem cells is a central aim in T cell regenerative medicine. To date, preferentially regenerating T lymphopoiesis in vivo from pluripotent stem cells (PSC) remains a practical challenge. Here we documented that synergistic and transient expression of Runx1 and Hoxa9 restricted in the time window of endothelial to hematopoietic transition and hematopoietic maturation stages induced in vitro from PSC (iR9-PSC) preferentially generated engraftable hematopoietic progenitors capable of homing to thymus and developing into mature T (iT) cells in primary and secondary immunodeficient recipients. Single-cell transcriptome and functional analyses illustrated the cellular trajectory of T lineage induction from PSC, unveiling the T-lineage specification determined at as early as hemogenic endothelial cell stage and identifying the bona fide pre-thymic progenitors. The iT cells distributed normally in central and peripheral lymphoid organs and exhibited abundant TCR{beta} repertoire. The regenerative T lymphopoiesis rescued the immune-surveillance ability in immunodeficient mice. Furthermore, gene-edited iR9-PSC produced tumor-specific-T cells in vivo that effectively eradicated tumor cells. This study provides insight into universal generation of functional and therapeutic T lymphopoiesis from the unlimited and editable PSC source.

immunology↗

bioRxiv2018

GWAS using 2b-RAD sequencing identified three mastitis important SNPs via two-stage association analysis in Chinese Holstein cows.

BackgroundBovine mastitis is a key disease restricting developing global dairy industry. Genomic wide association studies (GWAS) provided a convenient way to understand the biological basis of mastitis and better prevent or treat the disease. 2b-RADseq is a reduced-representation sequencing that offered a powerful method for genome-wide genetic marker development and genotyping. This study, GWAS using two-stage association analysis identified mastitis important genes single nucleotide polymorphisms (SNP) in Chinese Holstein cows.\n\nResultsIn the selected Chinese Holstein cows population, we identified 10,058 SNPs and predicted their allele frequencies. In stage I, 42 significant SNPs screened out in Chinese Holstein cows via Bayesian (P<0.001), while logistic regression model identified 51 SNPs (P<0.01). Twenty-seven significant SNPs appeared simultaneously in both analytical models, which of them only three significant SNPs (rs75762330, C>T, PIC=0.2999; rs88640083, A>G, PIC=0.1676; rs20438858, G>A, PIC=0.3366) located in non-coding region (introns and intergenic) screened out associated with inflammation or immune response. GO enrichment analysis showed that they annotated to three genes (PTK2B, SYK and TNFRSF21), respectively. Stage II? case-control study used to verify three important SNPs associated with dairy cows mastitis traits in independent population. Data suggested that the correlation between these three SNPs (rs75762330, P<0.025; rs88640083, P<0.005; rs20438858, P<0.001) and mastitis traits in dairy cows were consistent with stage I.\n\nConclusionTwo-stage association analysis approved that three significant SNPs associated with mastitis traits in Chinese Holstein cows. Gene function analysis indicated that three genes (PTK2B, SYK and TNFRSF21) involved in inflammation and immune response of dairy cows. Suggesting that they as new candidate genes have an impact on mastitis susceptibility (PTK2B and SYK, OR>1) or resistance (TNFRSF21, OR<1) in Chinese Holstein cows.

genomics↗