Cell Regeneration最新文献

The regenerative capacity of the adult mammalian heart remains a formidable challenge in biological research. Despite extensive investigations into the loss of regenerative potential during evolution and development, unlocking the mechanisms governing cardiomyocyte proliferation remains elusive. Two recent groundbreaking studies have provided fresh perspectives on mitochondrial-to-nuclear communication, shedding light on novel factors that regulate cardiomyocyte proliferation. The studies identified two mitochondrial processes, fatty acid oxidation and protein translation, as key players in restricting cardiomyocyte proliferation. Inhibition of these processes led to increased cell cycle activity in cardiomyocytes, mediated by reduction in H3k4me3 levels through accumulated α-ketoglutarate (αKG), and activation of the mitochondrial unfolded protein response (UPR^mt), respectively. In this research highlight, we discuss the novel insights into mitochondrial-to-nuclear communication presented in these studies, the broad implications in cardiomyocyte biology and cardiovascular diseases, as well as the intriguing scientific questions inspired by the studies that may facilitate future investigations into the detailed molecular mechanisms of cardiomyocyte metabolism, proliferation, and mitochondrial-to-nuclear communications.

Low back pain (LBP) mainly emerges from intervertebral disc (IVD) degeneration. However, the failing mechanism of IVD ́s components, like the annulus fibrosus (AF) and nucleus pulposus (NP), leading to IVD degeneration/herniation is still poorly understood. Moreover, the specific role of cellular populations and molecular pathways involved in the inflammatory process associated with IVD herniation remains to be highlighted. The limited knowledge of inflammation associated with the initial steps of herniation and the lack of suitable models to mimic human IVD ́s complexity are some of the reasons for that. It has become essential to enhance the knowledge of cellular and molecular key players for AF and NP cells during inflammatory-driven degeneration. Due to unique properties of immunomodulation and pluripotency, mesenchymal stem cells (MSCs) have attained diverse recognition in this field of bone and cartilage regeneration. MSCs therapy has been particularly valuable in facilitating repair of damaged tissues and may benefit in mitigating inflammation' degenerative events. Therefore, this review article conducts comprehensive research to further understand the intertwine between the mechanisms of action of IVD components and therapeutic potential of MSCs, exploring their characteristics, how to optimize their use and establish them safely in distinct settings for LPB treatment.

A better understanding of how and why the regenerative capacity differs among species will not only provide insights into the regeneration process but also hold value for the development of regenerative medicine and the improvement of healing procedures. In a recent Nature article, Zhulyn et al. identify a critical role played by the activation of mechanistic target of rapamycin complex 1 (mTORC1) signaling in enhancing tissue regenerative capacity in animals.

The BMP (Bone morphogenetic protein) signaling pathway plays a central role in metazoan biology, intricately shaping embryonic development, maintaining tissue homeostasis, and influencing disease progression. In the context of cancer, BMP signaling exhibits context-dependent dynamics, spanning from tumor suppression to promotion. Cancer stem cells (CSCs), a modest subset of neoplastic cells with stem-like attributes, exert substantial influence by steering tumor growth, orchestrating therapy resistance, and contributing to relapse. A comprehensive grasp of the intricate interplay between CSCs and their microenvironment is pivotal for effective therapeutic strategies. Among the web of signaling pathways orchestrating cellular dynamics within CSCs, BMP signaling emerges as a vital conductor, overseeing CSC self-renewal, differentiation dynamics, and the intricate symphony within the tumor microenvironment. Moreover, BMP signaling's influence in cancer extends beyond CSCs, intricately regulating cellular migration, invasion, and metastasis. This multifaceted role underscores the imperative of comprehending BMP signaling's contributions to cancer, serving as the foundation for crafting precise therapies to navigate multifaceted challenges posed not only by CSCs but also by various dimensions of cancer progression. This article succinctly encapsulates the diverse roles of the BMP signaling pathway across different cancers, spanning glioblastoma multiforme (GBM), diffuse intrinsic pontine glioma (DIPG), colorectal cancer, acute myeloid leukemia (AML), lung cancer, prostate cancer, and osteosarcoma. It underscores the necessity of unraveling underlying mechanisms and molecular interactions. By delving into the intricate tapestry of BMP signaling's engagement in cancers, researchers pave the way for meticulously tailored therapies, adroitly leveraging its dualistic aspects-whether as a suppressor or promoter-to effectively counter the relentless march of tumor progression.

Whole-body regeneration is a multifaceted process that reinstates a body to its initial three-dimension size and structure after resection injury. It is well-known that signaling waves such as calcium and extracellular signal-related kinase (ERK) signaling waves can efficiently transmit information between tissues or cells. However, the mechanisms responsible for coordinating wound responses over long distances are largely unexplored. A recent study has reported that the propagation of ERK signaling waves via longitudinal body-wall muscles play an essential role in wound response and whole-body regeneration in planarians, underscoring the significance of feedback interactions between spatially distinct tissues during whole-body regeneration over long distances. These findings not only address the central questions of regenerative biology but also have potential implications for regenerative medicine.

Naïve pluripotent state can be obtained by several strategies from various types of cells, in which the cell fate roadmap as well as key biological events involved in the journey have been described in detail. Here, we carefully explored the chromatin accessibility dynamics during the primed-to-naïve transition by adopting a dual fluorescent reporter system and the assay for transposase-accessible chromatin (ATAC)-seq. Our results revealed critical chromatin remodeling events and highlight the discordance between chromatin accessibility and transcriptional activity. We further demonstrate that the differential epigenetic modifications and transcription factor (TF) activities may play a critical role in regulating gene expression, and account for the observed variations in gene expression despite similar chromatin landscapes.

In vitro gametogenesis (IVG) has been a topic of great interest in recent years not only because it allows for further exploration of mechanisms of germ cell development, but also because of its prospect for innovative medical applications especially for the treatment of infertility. Elucidation of the mechanisms underlying gamete development in vivo has inspired scientists to attempt to recapitulate the entire process of gametogenesis in vitro. While earlier studies have established IVG methods largely using pluripotent stem cells of embryonic origin, the scarcity of sources for these cells and the ethical issues involved in their use are serious limitations to the progress of IVG research especially in humans. However, with the emergence of induced pluripotent stem cells (iPSCs) due to the revolutionary discovery of dedifferentiation and reprogramming factors, IVG research has progressed remarkably in the last decade. This paper extensively reviews developments in IVG using iPSCs. First, the paper presents key concepts from groundwork studies on IVG including earlier researches demonstrating that IVG methods using embryonic stem cells (ESCs) also apply when using iPSCs. Techniques for the derivation of iPSCs are briefly discussed, highlighting the importance of generating transgene-free iPSCs with a high capacity for germline transmission to improve efficacy when used for IVG. The main part of the paper discusses recent advances in IVG research using iPSCs in various stages of gametogenesis. In addition, current clinical applications of IVG are presented, and potential future applications are discussed. Although IVG is still faced with many challenges in terms of technical issues, as well as efficacy and safety, novel IVG methodologies are emerging, and IVG using iPSCs may usher in the next era of reproductive medicine sooner than expected. This raises both ethical and social concerns and calls for the scientific community to cautiously develop IVG technology to ensure it is not only efficacious but also safe and adheres to social and ethical norms.