TET2 promotes tumor antigen presentation and T cell IFN-γ, which is enhanced by vitamin C.

Immune evasion by tumors is promoted by low T cell infiltration, ineffective T cell activity directed against the tumor, and reduced tumor antigen presentation. The TET2 DNA dioxygenase gene is frequently mutated in hematopoietic malignancies and loss of TET enzymatic activity is found in a variety of solid tumors. We showed previously that vitamin C (VC), a cofactor of TET2, enhances tumor-associated T cell recruitment and checkpoint inhibitor therapy responses in a TET2-dependent manner.

Endosteal stem cells at the bone-blood interface: A double-edged sword for rapid bone formation: Bone marrow endosteal stem cells provide a robust source of bone-making osteoblasts both in normal and abnormal bone formation.

Endosteal stem cells are a subclass of bone marrow skeletal stem cell populations that are particularly important for rapid bone formation occurring in growth and regeneration. These stem cells are strategically located near the bone surface in a specialized microenvironment of the endosteal niche. These stem cells are abundant in young stages but eventually depleted and replaced by other stem cell types residing in a non-endosteal perisinusoidal niche.

Bone marrow endosteal stem cells dictate active osteogenesis and aggressive tumorigenesis.

The bone marrow contains various populations of skeletal stem cells (SSCs) in the stromal compartment, which are important regulators of bone formation. It is well-described that leptin receptor (LepR) perivascular stromal cells provide a major source of bone-forming osteoblasts in adult and aged bone marrow. However, the identity of SSCs in young bone marrow and how they coordinate active bone formation remains unclear.

The fate of early perichondrial cells in developing bones.

In endochondral bone development, bone-forming osteoblasts and bone marrow stromal cells have dual origins in the fetal cartilage and its surrounding perichondrium. However, how early perichondrial cells distinctively contribute to developing bones remain unidentified. Here we show using in vivo cell-lineage analyses that Dlx5 fetal perichondrial cells marked by Dlx5-creER do not generate cartilage but sustainably contribute to cortical bone and marrow stromal compartments in a manner complementary to fetal chondrocyte derivatives under the regulation of Hedgehog signaling.

Left ventricular remodeling following aortic root and ascending aneurysm repair.

Objective: Adverse left ventricular remodeling due to a mismatch between stiffness of native aortic tissue and current polyester grafts may be under-recognized. This study was conducted to evaluate the impact of proximal aortic replacement on adverse remodeling of the left ventricle.

Materials And Methods: All aortic root and ascending aortic aneurysm patients were identified ( = 2,001, 2006-2019).

Single-Cell Transcriptomic Analysis Reveals Developmental Relationships and Specific Markers of Mouse Periodontium Cellular Subsets.

The periodontium is essential for supporting the functionality of the tooth, composed of diversity of mineralized and non-mineralized tissues such as the cementum, the periodontal ligament (PDL) and the alveolar bone. The periodontium is developmentally derived from the dental follicle (DF), a fibrous tissue surrounding the developing tooth bud. We previously showed through lineage-tracing experiments that DF contains mesenchymal progenitor cells expressing parathyroid hormone-related protein (PTHrP), which give rise to cells forming the periodontal attachment apparatus in a manner regulated by autocrine signaling through the PTH/PTHrP receptor.

Multimodal Mapping of the Tumor and Peripheral Blood Immune Landscape in Human Pancreatic Cancer.

Pancreatic ductal adenocarcinoma (PDA) is characterized by an immune-suppressive tumor microenvironment that renders it largely refractory to immunotherapy. We implemented a multimodal analysis approach to elucidate the immune landscape in PDA. Using a combination of CyTOF, single-cell RNA sequencing, and multiplex immunohistochemistry on patient tumors, matched blood, and non-malignant samples, we uncovered a complex network of immune-suppressive cellular interactions.

Intercellular Interactions of an Adipogenic CXCL12-Expressing Stromal Cell Subset in Murine Bone Marrow.

Bone marrow houses a multifunctional stromal cell population expressing C-X-C motif chemokine ligand 12 (CXCL12), termed CXCL12-abundant reticular (CAR) cells, that regulates osteogenesis and adipogenesis. The quiescent pre-adipocyte-like subset of CXCL12 stromal cells ("Adipo-CAR" cells) is localized to sinusoidal surfaces and particularly enriched for hematopoiesis-supporting cytokines. However, detailed characteristics of these CXCL12 pre-adipocyte-like stromal cells and how they contribute to marrow adipogenesis remain largely unknown.