Cells Of Origin Research Articles

A case of EBV-Negative Primary Intestinal Diffuse Large B Cell Lymphoma Involving Multiple Anatomic Sites and Lymph Nodes

Abstract Introduction/Objective Extranodal lymphomas in the gastrointestinal tract are rare, with colonic lymphomas representing less than 0.5% of colorectal neoplasms. The most common type is Non-Hodgkin lymphoma. Treatment typically involves chemotherapy and surgical resection, with prognosis depends on various factors including age, genetic alteration, and bone marrow involvement. Methods/Case Report An 82-year-old female patient presented with abdominal pain and constipation. Radiological imaging revealed a mass in the ascending colon extending to the ileum. Histological examination following biopsy revealed to be a diffuse large B-cell lymphoma (DLBCL) of germinal center origin. The resected specimen showed two separate centrally ulcerated fungating masses in the ileum (4 x 4 x 1 cm) and ascending colon (8.5 x 5 x 4 cm). Microscopic examination showed a diffuse infiltrate of large, discohesive, atypical lymphoid cells with vesicular chromatin and prominent nucleoli. Abundant mitoses and apoptotic bodies are evident. The lesional cells were diffusely infiltrating into the lamina propria, submucosa, muscularis propria, and serosa associated with geographic necrosis. The appendix was also transmurally involved by the neoplastic cells. Multiple pericolonic lymph nodes were also involved by the lesional cells (6/15). Immunnohistochemical stains showed the neoplastic cells are positive for CD20, CD10, BCL6, while negative for MUM1, BCL2, C-MYC, and EBER. Ki67 index was 70%. CMV was negative. FISH result for MYC gene rearrangement with reflex to BCL2 and BCL6 was negative, which excludes double/triple-hit high grade B-cell lymphomas. The patient received chemotherapy with R-CHOP after the surgery and stayed recurrence-free for 15 months. Results (if a Case Study enter NA) NA Conclusion We reported a case of EBV-negative primary intestinal diffuse large B-cell lymphoma with germinal center cell origin involving multiple anatomic sites and pericolonic lymph nodes in an elderly immunocompetent woman.

Developmentally controlled subcellular remodeling and VND-initiated vacuole-executed PCD module shape xylem-like cells in peat moss

Peat moss (Sphagnum) is a non-vascular higher plant with unique xylem-like hyaline (H) cells that are accompanied by photosynthetic chlorophyllous cells. These cellular structures play crucial roles in water storage and carbon sequestration. However, it is largely unknown how peat moss develops the H cells. This study systematically explored the Sphagnum Developmental Cell Atlas and Lineage and classified leaf cell development into two lineages with six stages (S0-S5) based on changes in key cellular traits, including the formation of spiral secondary cell walls (S4) and the presence of water pores (S5). Cell lineage-specific subcellular remodeling was transcriptionally regulated during leaf development, and vacuole-mediated clearance of organelles and cell death led to mature dead H cells. Interestingly, expression of land plant conserved Vascular-related NAC Domain (VND) genes correlated with H cell formation. Overall, these results suggest that the origination of xylem-like H cells is related to VND, likely through the neofunctionalization of vacuole-mediated cell death to attempt xylem formation in peat moss, suggesting potential uncoupling of xylem and phloem cell origins. This study positions peat moss as a potential model organism for studying integrative evolutionary cell biology.

PIWIL1 is recruited to centrosomes during mitosis in colorectal cancer cells and is linked to cell cycle progression

PIWI proteins, traditionally associated with germline development, have recently gained attention for their expression in various cancers, including colorectal cancer. However, the molecular mechanisms underlying their reactivation and impact on cancer initiation and progression remain elusive. Here, we found that PIWIL1 is expressed at relatively high levels in CRC-derived samples and cell lines, where it undergoes a dynamic relocalization to the centrosome during mitosis. Knockdown of PIWIL1 induces G2/M arrest associated with disruption of the mitotic spindle and aberrant metaphase events, highlighting its role in cell cycle progression. We also found that the expression of PIWIL1 is lost during the differentiation of Caco-2 cells into enterocytes and that PIWIL1 is expressed in cells at the base of the intestinal crypts in normal human colon tissue, where intestinal stem cells are known to reside. Thus, it is possible that the presence of PIWIL1 in cancer cells reflects a physiological role of this protein in stem cell maintenance, which would argue in favor of the proposed stem cell origin of CRC. Supporting this view, dedifferentiation of human fibroblasts into induced pluripotent stem cells (iPSCs) involves the reactivation of PIWIL2 expression, another member of the PIWI protein family. Overall, our findings suggest a role of PIWIL1 in mediating cell cycle dynamics, both in colorectal cancer cells and possibly also in intestinal stem cells. In a broader aspect, we provide evidence supporting an involvement of PIWI proteins in somatic stem cell maintenance, thus expanding the known non-gonadal functions of this protein family.

Podoplanin Expression in Early-Stage Colorectal Cancer-Associated Fibroblasts and Its Utility as a Diagnostic Marker for Colorectal Lesions.

(Background) Cancer-associated fibroblasts (CAFs) are major cancer stromal components. CAFs have diverse functions and cell origins. Podoplanin (PDPN), a lymphatic vessel marker, is also a CAF marker in certain cancers. On daily diagnosis of early colorectal carcinoma (CRC), PDPN upregulation in the stroma is often encountered, suggesting PDPN-positive CAFs have emerged. However, PDPN-positive CAFs in early CRC have not been studied well. (Methods) On immunohistochemistry, PDPN expression in the lamina propria or stroma of adenomas, early CRCs, and neuroendocrine tumors, their normal neighbors, and non-neoplastic colorectal lesions were compared. Single-cell RNA sequencing (scRNA-seq) of CRC was used to explore PDPNhigh CAFs' cell origins. (Results) Reticular cells or pericryptal fibroblasts in the lamina propria of adenomas and early CRCs showed higher PDPN expression than did normal mucosae and non-neoplastic lesions (p < 0.01). Pericryptal PDPN expression was a diagnostic feature of adenomas and early CRCs. scRNA-seq of CRCs highlighted that PDPNhigh CAFs had distinctly higher COL4A1, COL4A2, and WNT5A expression, unlike well-known CAFs characterized by high FAP, POSTN, or ACTA2 expression. (Conclusions) We demonstrated that pericryptal fibroblasts and reticular cells in the lamina propria are origins of early-stage CRC CAFs and thus have potential as a diagnostic marker for distinguishing colorectal non-neoplastic from neoplastic lesions.

The conserved genetic program of male germ cells uncovers ancient regulators of human spermatogenesis.

Male germ cells share a common origin across animal species, therefore they likely retain a conserved genetic program that defines their cellular identity. However, the unique evolutionary dynamics of male germ cells coupled with their widespread leaky transcription pose significant obstacles to the identification of the core spermatogenic program. Through network analysis of the spermatocyte transcriptome of vertebrate and invertebrate species, we describe the conserved evolutionary origin of metazoan male germ cells at the molecular level. We estimate the average functional requirement of a metazoan male germ cell to correspond to the expression of approximately 10,000 protein-coding genes, a third of which defines a genetic scaffold of deeply conserved genes that has been retained throughout evolution. Such scaffold contains a set of 79 functional associations between 104 gene expression regulators that represent a core component of the conserved genetic program of metazoan spermatogenesis. By genetically interfering with the acquisition and maintenance of male germ cell identity, we uncover 161 previously unknown spermatogenesis genes and three new potential genetic causes of human infertility. These findings emphasize the importance of evolutionary history on human reproductive disease and establish a cross-species analytical pipeline that can be repurposed to other cell types and pathologies.

Updates in Microglial Research with Respect to Brain Cancer

Microglia resides in the microenvironment of the central nervous system (CNS) and is thought to play a key role in the development and progression of brain cancer. This is because it was shown that microglia comprised a large portion of the total brain tumour mass. Besides, the origin of microglia cells in brain tumours is worth understanding as it is important to distinguish the resident macrophages from the circulating macrophages when discussing the pathology of brain tumours. Activated microgliosis has been linked to increased inflammatory mediators like cytokines, growth factors, matrix metalloproteinases (MMPs) and many more, which would facilitate tumourigenesis. Brain tumour cells also proliferate under the influence of signalling pathways, such as the toll-like receptor 2 signals. Vascular endothelial growth factor (VEGF) which is an angiogenic factor aids in the growth of tumour cells. Brain cancer cells rely on suppressing the effector arm of immune system to evade attacks by downregulating major histocompatibility complexes (MHC) class II molecules and inducing the conversion of microglia to an immunosuppressive phenotype. Glioblastoma stem cells (GSCs) that give rise to brain cancers communicate with microglia cells, which determines their growth and invasion potential. Understanding the molecular interactions of brain cancer and microglia cells would help unlock novel treatments via means of immunotherapy, immunosuppressants and utilising microglia cells to deliver nanoparticle drugs to effectively target and treat brain cancer.

Mesenchymal stem cell origin contributes to the antitumor effect of oncolytic virus carriers

Mesenchymal stem cell origin contributes to the antitumor effect of oncolytic virus carriers

Regional Variations In The Immunohistochemical Expression Of P75 NGF Receptors Between Term And Post-Term Human Placenta

Background: The placenta has lately attracted increased attention due to its potential as a significant source of many types of stem cells, such as trophoblastic, hematopoietic, epithelial, and mesenchymal stem cells (MSCs). Placental cells are readily and ethically obtainable. In addition, the human placenta has the potential to provide a significant quantity of stem cells that can be readily isolated, expanded, and differentiated into several kinds of cells. Both the maternal and the fetal components of MSCs are present in the human placenta. Previous investigations have found that the origin of mesenchymal stem cells has a significant impact on their capacity to treat diseases. As a result, placental MSCs have a lot of potential for therapeutic use. Compared to the immunomodulatory activity of MSCs derived from mothers, fetal MSCs have a higher capacity to promote immunological health. The p75 protein has been demonstrated to be the most effective marker for the isolation and identification of human bone marrow-derived mesenchymal stem cells. CD271 was considered a versatile marker that would allow the isolation and culture of multipotent stem cells derived from mesenchymal tissue. No prior work reported P75 NGFR utilized in placental tissues as a marker for mesenchymal stem cells in connection to various gestational ages (term, and post-term) and diverse placental locations including (chorionic plate and placental villi sides).

S1PR1 mediates Th17 cell migration from the thymus to the skin in health and disease.

Th17 cells play crucial roles in host defense and the pathogenesis of autoimmune diseases in the skin. While their differentiation mechanisms have been extensively studied, the origin of skin Th17 cells remains unclear. In this study, we analyzed single-cell RNA-sequencing data and identify the presence of Th17 cells in the human thymus. Thymic Th17 cells were characterized by high expression levels of Sphingosine-1-Phosphate Receptor 1 (S1PR1), a receptor crucial for T cell egress from lymphoid tissues. In mice, Th17 cell-specific knockout of S1pr1 resulted in the accumulation of Th17 cells in the thymus and a corresponding decrease in their numbers in the skin. Th17 cells that accumulated in the thymus exhibited a lower IL-17A production capacity compared to those in the skin, indicating that the local environment in the skin is important for maintaining the Th17 cell phenotype. Additionally, using a murine psoriasis model, we demonstrated that Th17 cell-specific knockout of S1pr1 reduced their migration to the inflamed skin, thereby ameliorating disease progression. Collectively, our data suggest that S1PR1 mediates Th17 cell migration from the thymus to the skin, thereby modulating their functional engagement in both homeostatic and inflammatory conditions.

Feeder cell training shapes the phenotype and function of in vitro expanded natural killer cells.

Natural killer (NK) cells are candidates for adoptive cell therapy, and the protocols for their activation and expansion profoundly influence their function and fate. The complexity of NK cell origin and feeder cell cues impacts the heterogeneity of expanded NK (eNK) cells. To explore this, we compared the phenotype and function of peripheral blood-derived NK (PB-NK) and umbilical cord blood-derived NK (UCB-NK) cells activated by common feeder cell lines, including K562, PLH, and 221.AEH. After first encounter, most PB-NK cells showed degranulation independently of cytokines production. Meanwhile, most UCB-NK cells did both. We observed that each feeder cell line uniquely influenced the activation, expansion, and ultimate fate of PB eNK and UCB eNK cells, determining whether they became cytokine producers or killer cells. In addition, they also affected the functional performance of NK cell subsets after expansion, that is, expanded conventional NK (ecNK) and expanded FcRγ- NK (eg-NK)cells. Hence, the regulation of eNK cell function largely depends on the NK cell source and the chosen expansion system. These results underscore the significance of selecting feeder cells for NK cell expansion from various sources, notably for customized adoptive cell therapies to yield cytokine-producing or cytotoxic eNK cells.

Facial angiosarcoma: A unique, non-purpuric presentation with good prognosis and unconventional management.

Cutaneous angiosarcoma is a rare, aggressive malignant neoplasm of vascular endothelial cell origin with a poor prognosis. The typical presentation of cutaneous angiosarcoma involves a progressive, bruise-like lesion on the head or neck.1 We present an atypical case of facial angiosarcoma in a 79-year-old white male arising as an asymmetric, non-purpuric swelling of the left nasal tip and ala, resembling an asymmetric rhinophyma. Several studies comparing face and scalp angiosarcomas have shown improved prognosis when angiosarcoma occurs on the face.2 Our case supports this trend noted in the literature. Angiosarcoma is typically treated with multiple modalities including surgery, radiotherapy, and chemotherapy. Our patient’s angiosarcoma was controlled with debulking surgery, radiation therapy, and Pembrolizumab (off-label use of immunotherapy). Patient is doing well 4 years later and will resume surgery or radiation if needed for any recurrence.

Unraveling developmental patterns and differentiation trajectories in a single developing internode of Moso Bamboo (Phyllostachys edulis)

Bamboo, a significant carbon sink and eco-friendly resource, possesses substantial economic value and ecological benefits. A single internode represents the fundamental unit of bamboo culm, yet research focusing on the pivotal cellular destinies and molecular mechanisms underpinning the growth and development of a single internode remains comparatively scarce. In the study, we pioneered the establishment of a high-resolution single-cell transcriptomic atlas for a single internode of Moso bamboo. Utilizing known marker genes, we identified six major cell clusters (meristem, epidermis, phloem, xylem, pre-xylem/phloem, and vascular bundle sheath) and found many potential marker genes in the internode of Moso bamboo. Subsequently, we reconstructed the developmental trajectories of the epidermis and vascular tissues and further unveiled the key regulatory factors determining cell fates. Moreover, ectopic expression of PheIAA15 in Arabidopsis thaliana resulted in a marked reduction in the number of vascular bundles within the stems, as well as a significant decrease in their cross-sectional areas, diverging from existing research in Arabidopsis. The interaction between PheIAA15 and PheWOX4c suggested a potential novel auxin response mechanism in Moso bamboo. We subsequently elucidated that PheIAA15 bound to the promoter region of PheCLE25, thereby down-regulating the expression of PheCLE25, whereas PheWOX4c can activate the transcription of PheCLE25, which suggested that these two factors regulated the expression of PheCLE25 through an antagonistic mechanism. This finding highlighted the critical role of the complex regulatory network established among these elements in the differentiation of vascular tissues in the internodes of Moso bamboo. Overall, the study fills a critical research void concerning internodal development in bamboo plants at the single-cell level, laying a foundation for future studies to unravel the origin and differentiation of vascular bundle cells during internode development in perennial Gramineous plants.

HPV and Penile Cancer: Epidemiology, Risk Factors, and Clinical Insights.

Penile cancer (PC) is a rare malignancy predominantly of squamous cell origin. Approximately 40% of penile tumors are associated with human papillomavirus (HPV) infection. Diagnosing PC remains challenging due to its rarity and variety of clinical presentations. Furthermore, the impact of HPV on the tumor immune microenvironment complicates clinical management, although recent advancements in immune checkpoint inhibitors (ICIs) have shown some efficacy in treating HPV-associated PC. Ongoing research efforts aim to develop oncologic treatments that target HPV-induced cellular modifications. Additionally, novel therapeutic vaccines and adoptive T-cell therapies targeting HPV oncoproteins represent emerging treatment modalities. Our review highlights the complex interplay between HPV and penile carcinogenesis, emphasizing its epidemiology, etiology, clinicopathological characteristics, and potential therapeutic implications.

Foam Cells: The Origin of Formation and Target for Plant-derived Bioactive Compounds.

Foam cells play a crucial role in the initiation and progression of atherosclerosis, a condition marked by the development and growth of plaques that narrow blood vessel lumens. This narrowing can prevent normal blood flow and, in severe cases, lead to plaque rupture and blood clot formation, which can cause stroke or myocardial infarction. The origin of foam cells is diverse, arising from monocytes, vascular smooth muscle cells, stem/progenitor cells, and dendritic and endothelial cells. In their attempt to eliminate excess lipoproteins and cholesterol, foam cells inadvertently contribute to plaque development and rupture. Cholesterol uptake, efflux, and esterification are the major processes regulating foam cell formation. Advances in technology, such as the identification of cell-surface markers for lineage tracing and single-cell RNA sequencing, have unveiled diverse molecular mechanisms involved in the formation of foam cells from different origins, offering new insights into plaque formation and potential targets for anti-foam cell therapies. In this review, we focus on recent studies exploringthe inhibitory effects of medicinal plants and their bioactive components on foam cell formation. Various mechanisms are explored, including the inhibition of cholesterol uptake and the up-regulation of cholesterol efflux, as well as the suppression of inflammatory and adhesion activities. Emphasizing a cellular target-based therapeutic approach, this review envisions the development of innovative plant-based medications for atherosclerosis treatment.

Establishment and characterization of a novel cell line derived from spotted sea bass Lateolabrax maculatus and its susceptibilities to iridoviruses

The spotted sea bass (Lateolabrax maculatus), which holds significant commercial value, is extensively cultivated in China, Japan, and Southeast Asian countries. This study reports the establishment and characterization of a novel continuous cell line, designated as LMK cells, derived from the kidney tissue of spotted sea bass, The LMK cell line, primarily composed of epithelial-like cells, has been successfully subcultured in Medium 199 supplemented with 10 % fetal bovine serum (FBS) for over 60 passages. Mitochondrial genome sequencing and cytochrome c oxidase subunit I gene amplification verified the origin of the LMK cells from L. maculatus, distinguishing them from L. japonicus. Optimal culture conditions for LMK cells at passage 35 were determined to be 10 % FBS at 27 °C. Chromosomal analysis indicated that the cell line possesses 48 chromosomes. To assess viral susceptibility, LMK cells were exposed to the red sea bream iridovirus and largemouth bass ranavirus. Both iridoviruses induced cytopathic effects within 3 days post-infection and triggered immune-related gene responses. This study demonstrates that the LMK cell line is a valuable resource for molecular, virological, and immunological research in L.maculatus and other sea bass species.

Cancer-associated fibroblast cell surface markers as potential biomarkers or therapeutic targets in lung cancer.

Cancer-associated fibroblasts (CAFs) are the vital constituent of the tumor microenvironment, and in communication with other cells, they contribute to tumor progression and metastasis. Fibroblasts are the proposed origin of CAFs, which are mediated by pro-inflammatory cytokines and the recruitment of immune cells akin to wound healing. Although various studies have identified different subpopulations of CAFs in lung cancer, the heterogeneity of CAFs, particularly in lung cancer, and their potential as a therapeutic target remain largely unknown. Notwithstanding CAFs were previously thought to have predominantly tumor-promoting features, their pro- or anti-tumorigenic properties may depend on various conditions and cell origins. The absence of distinct markers to identify CAF subpopulations presents obstacles to the successful therapeutic targeting and treatment of CAFs in cancer. Human clinical and animal studies targeting CAFs have shown that targeting CAFs exacerbates the disease progression, suggesting that subpopulations of CAFs may exert opposing functions in cancer progression. Therefore, it is essential to pinpoint specific markers capable of characterizing these subpopulations and revealing their mechanisms of function. The cell-specific surface markers of CAFs will serve as an initial step in investigating precise CAF subpopulations and their role in diagnosing and targeting therapy against cancer-promoting CAF subsets in lung cancer.

Exosomes of immune cell origin and their therapeutic potential for tumors

AbstractExosomes are nanoscale membrane vesicles identified by electron microscopy in 1946. They are approximately 30–150 nm in size. Originally, exosomes were thought to be used to eliminate excess components from cells to maintain their normal physiology. Later, it was found that the function and targeting of specific cellular components in exosomes have important implications for the regulation of cellular communication. In the last few years, exosomes have been linked to tumors, infections, and other diseases. New advances in cancer immunotherapy have occurred as a result of the identification of exosomes of immune cell origin, expanding the existing anticancer immune response. This article details exosomes derived from dendritic cells, T lymphocytes (CD4+ T cells, CD8+ T cells, and CAR‐T cells), natural killer cells, and their promising applications in tumor therapy.

The emerging view on the origin and early evolution of eukaryotic cells.

The origin of the eukaryotic cell, with its compartmentalized nature and generally large size compared with bacterial and archaeal cells, represents a cornerstone event in the evolution of complex life on Earth. In a process referred to as eukaryogenesis, the eukaryotic cell is believed to have evolved between approximately 1.8 and 2.7 billion years ago from its archaeal ancestors, with a symbiosis with a bacterial (proto-mitochondrial) partner being a key event. In the tree of life, the branch separating the first from the last common ancestor of all eukaryotes is long and lacks evolutionary intermediates. As a result, the timing and driving forces of the emergence of complex eukaryotic features remain poorly understood. During the past decade, environmental and comparative genomic studies have revealed vital details about the identity and nature of the host cell and the proto-mitochondrial endosymbiont, enabling a critical reappraisal of hypotheses underlying the symbiotic origin of the eukaryotic cell. Here we outline our current understanding of the key players and events underlying the emergence of cellular complexity during the prokaryote-to-eukaryote transition and discuss potential avenues of future research that might provide new insights into the enigmatic origin of the eukaryotic cell.

The origin of ovarian Leydig cells: a possibly solved enigma?

Over the years, the origin of ovarian Leydig cells has been, and still is, a topic subject to deep debate. Seven years ago, we proposed that this origin resided in intraneural elements that came from a possible reservoir of neural crest cells, a reservoir that may be located in the ganglia of the celiac plexus. We believe we have found the evidence necessary to prove this hypothesis.

705P Subsequent malignant neoplasms (SMN) in patients with germ cell tumor of the testis (TGCT): Implications on a genetic vs stem cell origin of cancers

705P Subsequent malignant neoplasms (SMN) in patients with germ cell tumor of the testis (TGCT): Implications on a genetic vs stem cell origin of cancers