Biology subjects

DING, C.

Publications and source records attributed to DING, C..

3 recordsLinked to original sources

bioRxiv2026

Male-biased triploidy in Populus tremuloides and genomic structure of its southern relict populations

PremiseIsolated populations at the southern range edge of aspen (Populus tremuloides Michx.) offer a unique opportunity to study ploidy, clonality and distribution of sex under arid, high-elevation conditions. We aimed to characterize such traits, including potential sex biases and associations with ploidy, investigating previously unexamined Texan populations in a range-wide genomic framework of genetic structure and demographic history of this keystone species. MethodsWe combined new genotypic data from western Texas (Davis Mountains, Big Bend, Guadalupe Mountains) with preexisting datasets, assessing range-wide genetic diversity, clonality, ploidy, and sex. We further conducted ADMIXTURE and phylogenetic analyses, reconstructed historical effective population sizes (Ne) with Stairway Plot 2. ResultsTexan stands revealed high clonality, with diploid and triploid genets. Most Davis and Guadalupe Mountain individuals clustered with a southwestern U.S. lineage of aspen, whereas Big Bend individuals grouped with a Mexican, demonstrating for the first time the continuous northward geographic distributions of allele frequencies in aspen coherent with phylogenetics. The significant male bias in sex ratios, particularly among triploids, suggests dimorphism in survival or reproduction. No effect of elevation on sex was identified. Demographic inference indicated an ancient bottleneck ([~]1-2 Mya) common to all six lineages, but more recent historical Ne trajectories differ between the northern and southern regions. ConclusionsThese findings shed light on how clonality, ploidy, and sex have interacted in shaping dioecious plant species, highlighting the importance of incorporating such information into projections of how climate change and habitat loss will affect their distribution, abundance, and the extinction risk of their marginal populations.

evolutionary biology↗

bioRxiv2024

B cell c-Maf signaling promotes tumor progression in animal models of pancreatic cancer and melanoma

BackgroundThe role of B cells in anti-tumor immunity remains controversial, with studies suggesting the pro-tumor and anti-tumor activity. This controversy may be due to the heterogeneity in B cell populations, as the balance among the subtypes may impact tumor progression. The immunosuppressive regulatory B cells (Breg) release IL-10 but only represent a minor population. Additionally, tumor-specific antibodies (Ab) also exhibit anti-tumor and pro-tumor function dependent on the Ab isotype. Transcription factor c-Maf has been suggested to contribute to the regulation of IL-10 in Breg, but the role of B cell c-Maf signaling in anti-tumor immunity and regulating antibody responses remain unknown. MethodsConditional B cell c-Maf knockout (KO) and control mice were used to establish a KPC pancreatic cancer model and B16.F10 melanoma model. Tumor progression was evaluated. B cell and T cell phenotypes were determined by flow cytometry, mass cytometry, and cytokine/chemokine profiling. Differentially expressed genes in B cells were examined by using RNA-seq. Peripheral blood samples were collected from healthy donors and melanoma patients for B cell phenotyping. ResultsCompared to B cells from spleen and lymph nodes, B cells in the pancreas exhibited significantly less follicular phenotype and higher IL-10 production in naive mice. c-Maf deficiency resulted in a significant reduction of CD9+ IL-10-producing Breg in the pancreas. PDAC progression resulted in accumulation of circulating B cells with follicular phenotype and less IL-10 production in the pancreas. Notably, B cell c-Maf deficiency delayed PDAC tumor progression and resulted in pro-inflammatory B cells. Further, tumor volume reduction and increased effective T cells in the tumor-draining lymph node (TDLN) were observed in B cell c-Maf KO mice in the B16.F10 melanoma model. RNA-seq analysis of isolated B cells revealed that B cell c-Maf signaling modulates immunoglobulin (Ig)-associated genes and tumor specific antibody production. We furthermore demonstrated c-Maf-positive B cell subsets and increase of IL-10-producing B cells after incubation with IL-4 and CD40L in the peripheral blood of melanoma patients. ConclusionOur study highlights that B cell c-Maf signaling drives tumor progression through the modulation of Breg, inflammatory responses, and tumor-specific Ab responses. What is already known on this topicThe net effect of B cells on tumor immunity depends on the balance of various B cell subtypes. c-Maf has been suggested to contribute to the regulation of IL-10 in regulatory B cells (Breg), but the role of B cell c-Maf signaling in anti-tumor immunity remains unknown. What this study addsThis study shown that B cell c-Maf signaling drives tumor progression in pancreatic cancer and melanoma. We defined different anti-tumor mechanisms of B cell c-Maf deficiency in two tumor models. Specifically, c-Maf signaling modulates the pro-inflammatory phenotype of B cells in the KPC tumor-bearing pancreas and tumor-specific antibody responses in tumor draining lymph nodes (TDLN) of melanoma. How this study might affect research, practice or policyThese studies indicate that inhibition of c-Maf signaling is a novel and promising approach for immunotherapy in pancreatic cancer and melanoma.

immunology↗

bioRxiv2022

Reactive myelopoiesis and FX-expressing monocyte-derived macrophages triggered by chemotherapy promote cancer lung metastasis

Chemotherapy offers long-term clinical benefits to many cancer patients. However, several pre-clinical studies have demonstrated that certain cytotoxic drugs enhance metastasis via multiple mechanisms. These studies have mainly focused on tumor cell-derived inflammation. The importance of host responses triggered by chemotherapy in regulating cancer metastasis has not been fully explored. Here, we showed that multi-dose Gemcitabine (GEM) treatment promoted breast cancer lung metastasis in a transgenic spontaneous breast cancer animal model. Both CCR2+ macrophages and monocytes were increased in the lungs of GEM-treated mice. Further, the increase of CCR2+ macrophages and monocytes were observed in naive (tumor-free) mice after GEM treatment. These changes were largely caused by chemotherapy-induced reactive myelopoiesis that are biased toward monocyte development. Mechanistically, enhanced production of mitochondrial ROS (mtROS) was observed in GEM-treated BM LSK cells and monocytes. Treatment with the mitochondrial targeted antioxidant abrogated GEM induced hyper differentiation of BM progenitors. In addition, GEM treatment induced up-regulation of host cell-derived CCL2, and CCL2/CCR2 axis played essential role in the pro-metastatic host response induced by chemotherapy. Further, GEM and Paclitaxel (PTX) in combination with Doxorubicin (DOX) treatment resulted in up-regulation of coagulation factor X (FX) in lung interstitial macrophages. Targeting activated FX (FXa) using FXa inhibitor or F10 gene knockdown reduced pro-metastatic effect of chemotherapy-triggered host response. Together, these studies suggest a novel mechanism for chemotherapy induced metastasis via the host response-induced accumulation of monocytes/macrophages and interplay between coagulation and inflammation in the lungs.

immunology↗