Cellular reprogramming最新文献

The phospholipase C (PLC) family plays a crucial role in the construction of biomembranes, cell growth, and signal transduction. PLC regulates multiple cellular processes by generating bioactive molecules such as inositol-1,4,5-triphosphate (IP₃) and diacylglycerol (DAG). These products propagate and regulate cellular signaling via calcium (Ca²⁺) mobilization and activation of protein kinase C (PKC), other kinases, and ion channels. Recently, the function of PLC delta 3 (PLCδ3) has been arousing great interests in the basic research of neoplastic diseases. It is demonstrated to affect multiple parts of tumor progression and promote glycolysis reprogramming. However, currently there are no conclusive reports regarding the mechanism of PLCδ3-mediated tumor progression and its importance as a prognostic biomarker in specific neoplastic diseases. Therefore, the present article aimed to illustrate (1) the correlation between the function of phospholipases in PLC family and tumor progression; (2) the PLCδ3-mediated tumor progression, mainly focusing on the signal transduction and regulation; and (3) its potential mechanism and vital targets involved in multiple malignancies.

The mammalian olfactory neuronal lineage is regenerative, and accordingly, maintains a population of pluripotent cells that replenish olfactory sensory neurons and other olfactory cell types during the life of the animal. Moreover, in response to acute injury, the early transit amplifying cells along the olfactory sensory neuronal lineage are able to de-differentiate to shift resources in support of tissue restoration. In order to further explore plasticity of various cellular stages along the olfactory sensory neuronal lineage, we challenged the epigenetic stability of olfactory placode-derived cell lines that model immature olfactory sensory neuronal stages. We found that perturbation of the Ehmt2 chromatin modifier transformed the growth properties, morphology, and gene expression profiles toward states with several stem cell characteristics. This transformation was dependent on continued expression of the large T-antigen, and was enhanced by Sox2 over-expression. These findings may provide momentum for exploring inherent cellular plasticity within early cell types of the olfactory lineage, as well as potentially add to our knowledge of cellular reprogramming.

The reprogramming of somatic cells into different lineages by transdifferentiation holds great promise for regenerative medicine and replacement therapies. However, a recent report by Radwan et al. (PNAS, 2024) finds that transdifferentiated cells fail to fully adopt the DNA methylation profiles of their new lineage. This has important implications regarding the viability of transdifferentiation as a strategy for cell replacement therapy.

Since its first use in 1922, insulin therapy has transformed diabetes from a fatal disease to a manageable condition. However, long-term insulin injections lead to significant complications. β-cell replacement, derived from either a limited number of deceased donors or embryonic stem cells, offers an encouraging alternative. While these procedures allow patients to be insulin-independent, they still require systemic immunosuppressants to prevent graft rejection, which poses immunological challenges. Direct reprogramming holds considerable promise as a method for generating β-cells from various sources, enabling autologous therapies that mitigate the risk of immune rejection and eliminate the need to harvest cells from embryos. This review provides an overview of the latest advances in direct reprogramming strategies, with a focus on key transcriptional regulators that drive phenotypic conversion and maintenance of various cell types into β-like cells.

The decrease of endometrial receptivity leads to repeated implantation failure (RIF) during in vitro fertilization and embryo transfer. To explore the therapeutic potential of menstrual blood-derived mesenchymal stem cells (MenSCs) in addressing RIF, we established a murine model of embryonic implantation dysfunction using mifepristone. Subsequently, we administered MenSCs to these mice via tail vein injection and assessed their impact on the implantation and pregnancy rates of the affected mice. Furthermore, we conducted immunohistochemical staining on uterine tissues from these mice to examine the expression of endometrial receptivity markers, specifically vascular endothelial growth factor (VEGF)-A, HAND2, and HOXA10 following MenSCs transplantation. In parallel, we conducted in vitro studies to elucidate the molecular mechanisms of cell therapy by measuring the expression levels of VEGF-A, HAND2, and HOXA10 in endometrial stromal cells using real-time PCR and western blotting. In our mifepristone-induced mouse models, we observed a reduction in both pregnancy rates and implantation sites; however, these parameters were significantly improved after MenSCs transplantation. Similarly, the expression levels of VEGF-A, HAND2, and HOXA10 in the uterine tissues of the mifepristone group were diminished, but these levels were restored following MenSCs therapy. In vitro, after mifepristone treating, the expression of VEGF-A, HAND2, and HOXA10 decreased in endometrial stromal cells, but their expression increased after MenSCs coculture supernatant. In conclusion, these results demonstrated that MenSCs transplantation could increase endometrial receptivity by upregulating VEGF-A, HAND2, and HOXA10 expression. This study suggests MenSCs as a novel stem cell candidate in the treatment of RIF.

A Transcriptional Ridge in the Waddington Landscape. The Waddington landscape model, proposed in 1957, provides a powerful framework for understanding cell fate determination (Waddington, 1957). As development progresses, cells become restricted to distinct fates, separated by high "ridges" that prevent identity switching. A recent study in Nature Genetics uncovers such a ridge in hepatocyte lineage specification (Lim et al., 2025). Lim et al. report that prospero homeobox protein 1 (PROX1) acts as a hepatocyte-specific safeguard repressor, ensuring lineage stability by actively suppressing alternative cell fates and preventing cholangiocarcinoma development.

By dissecting metabolic and epigenetic features imposed by ageing in cardiomyocyte conversion from fetal and adult mouse fibroblasts, Santos et al. describe that metabolic modulation can enhance direct cardiac reprogramming.

Neuronal direct cell reprogramming approach allows direct conversion of somatic cells into neurons via forced expression of neuronal cell-lineage transcription factors (TFs). These so-called induced neuronal cells have significant potential as research tools and for therapeutic applications, such as in cell replacement therapy. However, the optimization of TF delivery strategies is crucial to reach clinical practice. In this review, we outlined the currently explored delivery technologies in neuronal direct cell reprogramming and their limitations and advantages. The first employed delivery strategies were mainly integrating viral systems, such as lentiviruses that exert consistently high transgene expression in most cell types. On the other hand, viral systems cause major safety concerns, including the risk for insertional mutagenesis and inflammation. More recently, several safer nonviral delivery systems have been investigated as well; however, these systems generally exert inferior reprogramming efficiency compared with viral systems. Emerging delivery technologies could provide new opportunities in the achievement of safe and effective delivery for neuronal direct cell reprogramming.