Microbiome and Hemato-immune Aging.

The microbiome is a highly complex and diverse symbiotic component that undergoes dynamic changes with the organismal aging. Microbial perturbations, termed dysbiosis, exert strong influence on dysregulating the bone marrow niche and subsequently promoting the aging of hematopoietic and immune system. Accumulating studies have revealed the substantial impact of intestinal microbiome on the initiation and progression of age-related hematologic alteration and diseases, such as clonal hematopoiesis and blood cancers.

Inflammation Regulates Haematopoietic Stem Cells and Their Niche.

Haematopoietic stem cells (HSCs) reside in the bone marrow and are supported by the specialised microenvironment, a niche to maintain HSC quiescence. To deal with haematopoietic equilibrium disrupted during inflammation, HSCs are activated from quiescence directly and indirectly to generate more mature immune cells, especially the myeloid lineage cells. In the process of proliferation and differentiation, HSCs gradually lose their self-renewal potential.

CD271CD51PALLADIN Human Mesenchymal Stromal Cells Possess Enhanced Ossicle-Forming Potential.

Human mesenchymal stem/stromal cells (hMSCs), when engrafted into immunodeficient mice, can form ectopic bone organs with hematopoietic stem cell (HSC) supportive functions. However, the ability to do so, through a cartilage intermediate, appears limited to 30% of donor bone marrow samples. In this study, we characterize the heterogeneous nature of hMSCs and their ability to efficiently form humanized ossicles observed in "good donors" to correlate with the frequency and functionality of chondrocyte progenitors.

The interplay of UBE2T and Mule in regulating Wnt/β-catenin activation to promote hepatocellular carcinoma progression.

Emerging evidence indicates the role of cancer stem cells (CSCs) in tumor relapse and therapeutic resistance in patients with hepatocellular carcinoma (HCC). To identify novel targets against liver CSCs, an integrative analysis of publicly available datasets involving HCC clinical and stemness-related data was employed to select genes that play crucial roles in HCC via regulation of liver CSCs. We revealed an enrichment of an interstrand cross-link repair pathway, in which ubiquitin-conjugating enzyme E2 T (UBE2T) was the most significantly upregulated.

The CCCTC-binding factor (CTCF)-forkhead box protein M1 axis regulates tumour growth and metastasis in hepatocellular carcinoma.

CCCTC-binding factor (CTCF) is a DNA-binding protein that interacts with a large number of highly divergent target sequences throughout the genome. It is implicated in a variety of functions, including chromatin organization and transcriptional control. The functional role of CTCF in tumour pathogenesis remains elusive.

Stearoyl-CoA desaturase regulates sorafenib resistance via modulation of ER stress-induced differentiation.

Background & Aims: We investigated the functional role and clinical significance of stearoyl-CoA desaturase-1 (SCD1) mediated endoplasmic reticulum (ER) stress in regulating liver tumor-initiating cells (T-ICs) and sorafenib resistance, with the aim of developing a novel therapeutic strategy against hepatocellular carcinomas (HCCs).

Methods: We evaluated the clinic-pathological relevance of SCD1 and its correlation with sorafenib resistance in large cohorts of HCC clinical samples by qPCR and immunohistochemical analyses. Lentiviral-based overexpression and knockdown approaches were performed to characterize the functional roles of SCD1 in regulating liver T-ICs and sorafenib resistance.

Cancer Stem Cells and Their Microenvironment: Biology and Therapeutic Implications.

Tumor consists of heterogeneous cancer cells including cancer stem cells (CSCs) that can terminally differentiate into tumor bulk. Normal stem cells in normal organs regulate self-renewal within a stem cell niche. Likewise, accumulating evidence has also suggested that CSCs are maintained extrinsically within the tumor microenvironment, which includes both cellular and physical factors.