Spatiotemporal Analysis of Mesenchymal Stem Cells Fate Determination by Inflammatory Niche Following Soft Tissue Injury at a Single-Cell Level.

Heterotopic ossification (HO), often arising in response to traumatic challenges, results from the aberrant osteochondral differentiation of mesenchymal stem cells (MSCs). Nevertheless, the impact of trauma-induced inflammatory exposure on MSC fate determination remains ambiguous. In this study, the cellular diversity within inflammatory lesions is elucidated, comprising MSCs and several innate and adaptive immune cells.

Prototypical innate immune mechanism hijacked by leukemia-initiating mutant stem cells for selective advantage and immune evasion in Ptpn11-associated juvenile myelomonocytic leukemia.

Juvenile myelomonocytic leukemia (JMML), a clonal hematologic malignancy, originates from mutated hematopoietic stem cells (HSCs). The mechanism sustaining the persistence of mutant stem cells, leading to leukemia development, remains elusive. In this study, we conducted comprehensive examination of gene expression profiles, transcriptional factor regulons, and cell compositions/interactions throughout various stages of tumor cell development in Ptpn11 mutation-associated JMML.

Phase separation of SHP2E76K promotes malignant transformation of mesenchymal stem cells by activating mitochondrial complexes.

Mesenchymal stem cells (MSCs), suffering from diverse gene hits, undergo malignant transformation and aberrant osteochondral differentiation. Src homology region 2-containing protein tyrosine phosphatase 2 (SHP2), a nonreceptor protein tyrosine phosphatase, regulates multicellular differentiation, proliferation, and transformation. However, the role of SHP2 in MSC fate determination remains unclear.

Advanced Progression for the Heterogeneity and Homeostasis of Intestinal Stem Cells.

Current understanding of the leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5) in intestinal stem cells (ISCs) is well established, however, the implications of ISC heterogeneity and homeostasis are poorly understood. Prior studies have provided important evidence for the association between heterogeneity of ISC pools with pathogenesis and therapeutic response of malignant disease. Leveraging the advantages of organoids and single cell RNA sequencing (scRNA-seq), glandular development has been simulated and cell heterogeneity has been clarified.

Arsenic exposure increases susceptibility to -induced malignancy in mouse embryonic fibroblasts through mitochondrial hypermetabolism.

Objective: To explore the synergistic effect and metabolic mechanism of chronic arsenic exposure and gain-of-function mutation on tumorigenesis.

Methods: Arsenic-transformed (WT-As) and -mutant (D61G-As) mouse embryonic fibroblasts (MEFs) were established by chronic treatment of low-dose arsenic. We used cell counting, plate colony and soft agar colony formation, and a nude mouse xenograft model to detect malignant transformation and tumorigenesis and .

Regulation of Malignant Myeloid Leukemia by Mesenchymal Stem Cells.

Bone marrow microenvironment (BMM) has been proven to have benefits for both normal hematopoietic stem cell niche and pathological leukemic stem cell niche. In fact, the pathological leukemia microenvironment reprograms bone marrow niche cells, especially mesenchymal stem cells for leukemia progression, chemoresistance and relapse. The growth and differentiation of MSCs are modulated by leukemia stem cells.

Berberine Attenuates Cell Motility Inhibiting Inflammation-Mediated Lysyl Hydroxylase-2 and Glycolysis.

Lysyl hydroxylase-2 (LH2) involves in the hydroxylation of telopeptide lysine residues during collagen deposition. Recent studies indicate that interleukin (IL)-6 generated by the chronic inflammation disease may trigger the LH2 expression to accelerate cell motility. Berberine is the alkaloid derived from the traditional Chinese medicine Coptis chinensis, which displays potential anti-inflammatory activity in multiple diseases.

Mapping Breast Cancer Microenvironment Through Single-Cell Omics.

Breast cancer development and progression rely not only on the proliferation of neoplastic cells but also on the significant heterogeneity in the surrounding tumor microenvironment. Its unique microenvironment, including tumor-infiltrating lymphocytes, complex myeloid cells, lipid-associated macrophages, cancer-associated fibroblasts (CAFs), and other molecules that promote the growth and migration of tumor cells, has been shown to play a crucial role in the occurrence, growth, and metastasis of breast cancer. However, a detailed understanding of the complex microenvironment in breast cancer remains largely unknown.

Neutrophil: A New Player in Metastatic Cancers.

The interaction between cancer cells and immune cells is important for the cancer development. However, much attention has been given to T cells and macrophages. Being the most abundant leukocytes in the blood, the functions of neutrophils in cancer have been underdetermined.

BMP-dependent, injury-induced stem cell niche as a mechanism of heterotopic ossification.

Background: Heterotopic ossification (HO), either acquired (aHO) or hereditary, such as fibrodysplasia ossificans progressiva (FOP), is a serious condition without effective treatment. Understanding of the core process of injury-induced HO is still severely limited.

Methods: Double-pulse thymidine analog labeling was used to explore the distinctive domains evolved in injury-induced lesions in an animal model of HO (Nse-BMP4).

Wnt signaling in physiological and pathological bone formation.

Wnt signaling, canonical or non-canonical, plays conserved roles in numerous physiological and pathological processes. However, it is well beyond the scope of this review to cover all functional aspects of Wnt signaling in different contexts at reasonable depth; therefore this review intends to cover only the roles of Wnt signaling in bone biology; more specifically, we intend to first update the roles of Wnt signaling in physiological bone process, including in osteogenesis and chondrogenesis, since recent years have witnessed tremendous progressions in this area, and then we seek to extend our understanding to the pathological bone process, especially to the heterotopic ossification (HO), even though the understanding of Wnt signaling in HO has been limited. We then further clarify the potential crosstalking between Wnt and other conserved signaling pathways, including FGF, GPCR and Hif1α pathways.