Frontiers in Cell and Developmental Biology最新文献

Mesenchymal stem cells (MSC) are fibroblast-like non-hematopoietic cells with self-renewal and differentiation capacity, and thereby great potential in regeneration and wound healing. MSC populations are heterogeneous not only inherently, but also among different model species. In particular, porcine MSC serve as a frequently used resource for translational research, due to pigs' distinctive closeness to human anatomy and physiology. However, information on gene expression profiles from porcine MSC and its dynamics during differentiation is sparse, especially with regard to cell surface and inner cell markers. In this study, we investigated the transcriptome of bone marrow-derived MSC and its differentiated cell types in a minipig breed for experimental research, known as Mini-LEWE, using bulk mRNA sequencing. Our data highlighted Rap1 signaling and downstream pathways PI3K-Akt and MAPK signaling as potential players for the maintenance of stemness of BM-MSC. In addition, we were able to link the process of differentiation to changes in the regulation of actin cytoskeleton. A total of 18 "BM-MSC differentiation driver markers" were identified, potentially promoting the process of differentiation into adipocytes, chondrocytes as well as osteocytes. Our results offer a new perspective on the molecular phenotype of porcine BM-MSC and the transcriptional responses in new differentiated progeny.

Exploring the evolutionary dynamics of lysozymes is critical for advancing our knowledge of adaptations in immune and digestive systems. Here, we characterize the distribution of a unique class of lysozymes known as g-type, which hydrolyze key components of bacterial cell walls. Notably, ctenophores, and choanoflagellates (the sister group of Metazoa), lack g-type lysozymes. We reveal a mosaic distribution of these genes, particularly within lophotrochozoans/spiralians, suggesting the horizontal gene transfer events from predatory myxobacteria played a role in their acquisition, enabling specialized dietary and defensive adaptations. We further identify two major groups of g-type lysozymes based on their widespread distribution in gastropods. Despite their sequence diversity, these lysozymes maintain conserved structural integrity that is crucial for enzymatic activity, underscoring independent evolutionary pathways where g-type lysozymes have developed functionalities typically associated with different lysozyme types in other species. Specifically, using Aplysia californica as a reference species, we identified three distinct g-type lysozyme genes: two are expressed in organs linked to both feeding and defense, and the third exhibits broader distribution, likely associated with immune functions. These findings advance our understanding of the evolutionary dynamics shaping the recruitment and mosaic functional diversification of these enzymes across metazoans, offering new insights into ecological physiology and physiological evolution as emerging fields.

Peripheral nerve repair remains a major clinical challenge, particularly in the pursuit of therapeutic approaches that ensure adequate recovery of patient's activity of daily living. Autografts are the gold standard in clinical practice for restoring lost sensorimotor functions nowadays. However, autografts have notable drawbacks, including dimensional mismatches and the need to sacrifice one function to restore another. Engineered nerve guidance conduits have therefore emerged as promising alternatives. While these conduits show surgical potential, their clinical use is currently limited to the repair of minor injuries, as their ability to reinnervate limiting gap lesions is still unsatisfactory. Therefore, improving patient functional recovery requires a deeper understanding of the cellular mechanisms involved in peripheral nerve regeneration and the development of therapeutic strategies that can precisely modulate these processes. Interest has grown in the use of external energy sources, such as light, ultrasound, electrical, and magnetic fields, to activate cellular pathways related to proliferation, differentiation, and migration. Recent research has explored combining these energy sources with tailored nanostructured materials as nanotransducers to enhance selectivity towards the target cells. This review aims to present the recent findings on this innovative strategy, discussing its potential to support nerve regeneration and its viability as an alternative to autologous transplantation.

Introduction: Following early cell specification and tenocyte differentiation at the sites of future tendons, very little is known about how tendon maturation into robust load-bearing tissue is regulated. Between embryonic day (E)16 and E18 in the chick, there is a rapid change in mechanical properties which is dependent on normal embryo movement. However, the tissue, cellular and molecular changes that contribute to this transition are not well defined.

Methods: Here we profiled aspects of late tendon development (collagen fibre alignment, cell organisation and Yap pathway activity), describing changes that coincide with tissue maturation. We compared effects of rigid (constant static loading) and flaccid (no loading) immobilisation to gain insight into developmental steps influenced by mechanical cues.

Results: We show that YAP signalling is active and responsive to movement in late tendon. Collagen fibre alignment increased over time and under static loading. Cells organise into end-to-end stacked columns with increased distance between adjacent columns, where collagen fibres are deposited; this organisation was lost following both types of immobilisation.

Discussion: We conclude that specific aspects of tendon maturation require controlled levels of dynamic muscle-generated stimulation. Such a developmental approach to understanding how tendons are constructed will inform future work to engineer improved tensile load-bearing tissues.

Introduction: Gastric cancer (GC) is an aggressive and heterogeneous malignancy marked by cellular and molecular diversity. In GC, cancer cells invade locally in the stomach at stage I and can progress to metastasis in distant organs by stage IV, where it often becomes fatal.

Methods: We analyzed gene expression profiles from 719 stage I and stage IV GC patients across seven public datasets, conducting functional enrichment analysis to identify a gene signature linked to disease progression. Additionally, we developed an in vitro model of a simplified extracellular matrix (ECM) for cell-based assays.

Results: Our analysis identified a progression-associated gene signature (APOD, COL1A2, FSTL1, GEM, LUM, and SPARC) that characterizes stage IV GC. This signature is associated with ECM organization and epithelial-to-mesenchymal transition (EMT), both of which influence the tumor microenvironment by promoting cell invasion and triggering EMT.

Discussion: This gene signature may help identify stage I GC patients at higher risk, offering potential utility in early-stage patient management. Furthermore, our experimental ECM model may serve as a platform for investigating molecular mechanisms underlying metastatic spread in gastric cancer.

S-Palmitoylation has been widely noticed and studied in a variety of diseases. Increasing evidence suggests that S-palmitoylation modification also plays a key role in Glioblastoma (GBM). The zDHHC family, as an important member of S-palmitoyltransferases, has received extensive attention for its function and mechanism in GBM which is one of the most common primary malignant tumors of the brain and has an adverse prognosis. This review focuses on the zDHHC family, essential S-palmitoyltransferases, and their involvement in GBM. By summarizing recent studies on zDHHC molecules in GBM, we highlight their significance in regulating critical processes such as cell proliferation, invasion, and apoptosis. Specifically, members of zDHHC3, zDHHC4, zDHHC5 and others affect key processes such as signal transduction and phenotypic transformation in GBM cells through different pathways, which in turn influence tumorigenesis and progression. This review systematically outlines the mechanism of zDHHC family-mediated S-palmitoylation modification in GBM, emphasizes its importance in the development of this disease, and provides potential targets and strategies for the treatment of GBM. It also offers theoretical foundations and insights for future research and clinical applications.

Over 90% of treatment failures in cancer therapy can be attributed to multidrug resistance (MDR), which can develop intracellularly or through various routes. Numerous pathways contribute to treatment resistance in cancer, but one of the most significant pathways is intracellular drug efflux and reduced drug concentrations within cells, which are controlled by overexpressed drug efflux pumps. As a member of the family of ABC transporter proteins, ABCC5 (ATP Binding Cassette Subfamily C Member 5) reduces the intracellular concentration of a drug and its subsequent effectiveness using an ATP-dependent method to pump the drug out of the cell. Numerous studies have demonstrated that ABCC5 is strongly linked to both poor prognosis and poor treatment response. In addition, elevated ABCC5 expression is noted in a wide variety of malignancies. Given that ABCC5 is regulated by several pathways in a broad range of cancer types, it is a prospective target for cancer treatment. This review examined the expression, structure, function, and role of ABCC5 in various cancer types.

Introduction: The lips fulfill various critical physiological roles besides being viewed as a fundamental aesthetic feature contributing to the perception of health and beauty. Therefore, any lip injury, abnormality, or congenital malformation, such as cleft lip, needs special attention in order to restore proper lip function and aesthetics. To achieve this goal, a better understanding of the complex lip anatomy, function, and biology is required, which can only be provided by basic research endeavors. However, the current lack of clinically relevant human lip cells and three-dimensional in vitro lip models, capable of replacing ethically questionable animal experimentations, represents a significant limitation in this area of research.

Methods: To address these limitations, we aimed to pioneer the introduction of immortalized healthy lip- and cleft lip-derived keratinocytes. Primary keratinocytes were isolated from patients' samples and immortalized by introducing the catalytic domain of telomerase, combined with the targeted knockdown of the cell cycle inhibitor gene, p16 ^INK4A . We then focused on validating the newly established cell lines by comparing their genetic stability and key phenotypic features with their primary keratinocyte counterparts.

Results: The newly established immortalized keratinocyte cell lines demonstrated genetic stability and preserved the main phenotypic characteristics of primary keratinocytes, such as cellular morphology and differentiation capacity. Three-dimensional lip models, generated using these cell lines, proved to be effective and convenient platforms for screening applications, including wound healing and microbial infection of the lip epithelium.

Discussion: The establishment of immortalized keratinocytes derived from healthy and cleft lips represents a significant achievement in lip research. These cell lines and the associated three-dimensional lip models are valuable tools that can be used as convenient screening platforms for various assays in a multitude of lip-related research areas, including dermatology, skin care, wound healing, tissue engineering, and craniofacial anomalies. This work opens new avenues in studying lip abnormalities and provides unique tools for personalized medicine approaches beneficial to patients.

Transglutaminase 2 (TG2) is a widely distributed multifunctional protein with various enzymatic and non-enzymatic activities. It is becoming increasingly evident that high levels of TG2 in tumors induce the occurrence of epithelial to mesenchymal transition (EMT) and the acquisition of stem cell-like phenotypes, promoting tumor metastasis and drug resistance. By regulating intracellular and extracellular signaling pathways, TG2 promotes breast cancer metastasis to lung, brain, liver and bone, as well as resistance to various chemotherapy drugs including docetaxel, doxorubicin, platinum and neratinib. More importantly, recent studies described the involvement of TG2 in PD-1/PD-L1 inhibitors resistance. An in-depth understanding of the role that TG2 plays in the progression of metastasis and drug resistance will offer new therapeutic targets for breast cancer treatment. This review covers the extensive and rapidly growing field of the role of TG2 in breast cancer. Based on the role of TG2 in EMT, we summarize TG2-related signaling pathways in breast cancer metastasis and drug resistance and discuss TG2 as a therapeutic target.