Cell Regeneration最新文献

Cardiovascular disease is the leading cause of mortality with very limited therapeutic interventions, thus holding great hope for cardiac regenerative medicine. A recent work from Martin's laboratory reports their identification of a fetal-like cardiomyocyte progenitor, adult cardiomyocyte type 2 (aCM2), and its potential interactions with C3⁺ cardiac fibroblasts and C3ar1⁺ macrophages to form a regenerative cellular triad, which is only present in the regenerative heart models, YAP5SA-expressing adult hearts and neonatal hearts. The complement signaling is essential for cellular interactions in this regenerative triad. This Highlight summarizes these major findings and provides brief perspectives on the impact of this regenerative niche during cardiac regeneration in the future.

Intestinal epithelium regeneration is crucial for homeostatic maintenance of the intestinal functions. A recent study published in Nature uncovers tuft cells as an unexpected key player in the regenerative process. Human tuft cells, traditionally recognized for their involvement in immune defense and pathogen protection, were found to exhibit stem cell-like properties following radiation-induced injury. These cells not only resist damage but also have the ability to generate functional stem cells, promoting the repair of the intestinal epithelium. This finding suggests that tuft cells may function as a reserve pool of stem cells, essential for efficient intestinal regeneration after injury.

Human stem cells are undifferentiated cells with the capacity for self-renewal and differentiation into distinct cell lineages, playing important role in the development and maintenance of diverse tissues and organs. The microenvironment of stem cell provides crucial factors and components that exert significant influence over the determination of cell fate. Among these factors, cytokines from the transforming growth factor β (TGFβ) superfamily, including TGFβ, bone morphogenic protein (BMP), Activin and Nodal, have been identified as important regulators governing stem cell maintenance and differentiation. In this review, we present a comprehensive overview of the pivotal roles played by TGFβ superfamily signaling in governing human embryonic stem cells, somatic stem cells, induced pluripotent stem cells, and cancer stem cells. Furthermore, we summarize the latest research and advancements of TGFβ family in various cancer stem cells and stem cell-based therapy, discussing their potential clinical applications in cancer therapy and regeneration medicine.

Macrophages are crucial in the heart's development, function, and injury. As part of the innate immune system, they act as the first line of defense during cardiac injury and repair. After events such as myocardial infarction or myocarditis, numerous macrophages are recruited to the affected areas of the heart to clear dead cells and facilitate tissue repair. This review summarizes the roles of resident and recruited macrophages in developing cardiovascular diseases. We also describe how macrophage phenotypes dynamically change within the cardiovascular disease microenvironment, exhibiting distinct pro-inflammatory and anti-inflammatory functions. Recent studies reveal the values of targeting macrophages in cardiovascular diseases treatment and the novel bioengineering technologies facilitate engineered macrophages as a promising therapeutic strategy. Engineered macrophages have strong natural tropism and infiltration for cardiovascular diseases aiming to reduce inflammatory response, inhibit excessive fibrosis, restore heart function and promote heart regeneration. We also discuss recent studies highlighting therapeutic strategies and new approaches targeting engineered macrophages, which can aid in heart injury recovery.

The intestine, is responsible for food digestion, nutrient absorption, endocrine secretion, food residue excretion, and immune defense. These function performances are based on the intricate composition of intestinal epithelial cells, encompassing differentiated mature cells, rapidly proliferative cells, and intestinal stem cells. Although the characteristics of these cell types are well-documented, in-depth exploration of their representative markers and transcription factors is critical for comprehensive cell fate trajectory analysis. Here, we unveiled the feature genes in different cell types of the human and mouse gut through single-cell RNA sequencing analysis. Further, the locations of some specific transcription factors and membrane proteins were determined by immunofluorescence staining, and their role in regulating the proliferation and differentiation of intestinal epithelial cells were explored by CRISPR/Cas9 knockout. Therefore, this study not only reports new markers for various intestinal epithelial cell types but also elucidates the involvement of relevant genes in the determination of epithelial cell fate and maintenance of stem cell homeostasis, which facilitates the tracing and functional elucidation of intestinal epithelial cells.

Prostate cancer is a malignant tumor of the male urological system with the highest incidence rate in the world, which seriously threatens the life and health of middle-aged and elderly men. The progression of prostate cancer involves the interaction between tumor cells and tumor microenvironment. Understanding the mechanisms of prostate cancer pathogenesis and disease progression is important to guide diagnosis and therapy. The emergence of single-cell RNA sequencing (scRNA-seq) and spatial transcriptome sequencing (ST-seq) technologies has brought breakthroughs in the study of prostate cancer. It makes up for the defects of traditional techniques such as fluorescence-activated cell sorting that are difficult to elucidate cell-specific gene expression. This review summarized the heterogeneity and functional changes of prostate cancer and tumor microenvironment revealed by scRNA-seq and ST-seq, aims to provide a reference for the optimal diagnosis and treatment of prostate cancer.

Emerging evidence illustrates that osteoclasts (OCs) play diverse roles beyond bone resorption, contributing significantly to bone formation and regeneration. Despite this, OCs remain mysterious cells, with aspects of their lifespan-from origin, fusion, alterations in cellular characteristics, to functions-remaining incompletely understood. Recent studies have identified that embryonic osteoclastogenesis is primarily driven by osteoclast precursors (OCPs) derived from erythromyeloid progenitors (EMPs). These precursor cells subsequently fuse into OCs essential for normal bone development and repair. Postnatally, hematopoietic stem cells (HSCs) become the primary source of OCs, gradually replacing EMP-derived OCs and assuming functional roles in adulthood. The absence of OCs during bone development results in bone structure malformation, including abnormal bone marrow cavity formation and shorter long bones. Additionally, OCs are reported to have intimate interactions with blood vessels, influencing bone formation and repair through angiogenesis regulation. Upon biomaterial implantation, activation of the innate immune system ensues immediately. OCs, originating from macrophages, closely interact with the immune system. Furthermore, evidence from material-induced bone formation events suggests that OCs are pivotal in these de novo bone formation processes. Nevertheless, achieving a pure OC culture remains challenging, and interpreting OC functions in vivo faces difficulties due to the presence of other multinucleated cells around bone-forming biomaterials. We here describe the fusion characteristics of OCPs and summarize reliable markers and morphological changes in OCs during their fusion process, providing guidance for researchers in identifying OCs both in vitro and in vivo. This review focuses on OC formation, characterization, and the roles of OCs beyond resorption in various bone pathophysiological processes. Finally, therapeutic strategies targeting OCs are discussed.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by massive neuronal loss in the brain. Both cortical glutamatergic neurons and basal forebrain cholinergic neurons (BFCNs) in the AD brain are selectively vulnerable. The degeneration and dysfunction of these two subtypes of neurons are closely associated with the cognitive decline of AD patients. The determination of cellular and molecular mechanisms involved in AD pathogenesis, especially in the early stage, will largely facilitate the understanding of this disease and the development of proper intervention strategies. However, due to the inaccessibility of living neurons in the brains of patients, it remains unclear how cortical glutamatergic neurons and BFCNs respond to pathological stress in the early stage of AD. In this study, we established in vitro differentiation systems that can efficiently differentiate patient-derived iPSCs into BFCNs. We found that AD-BFCNs secreted less Aβ peptide than cortical glutamatergic neurons did, even though the Aβ42/Aβ40 ratio was comparable to that of cortical glutamatergic neurons. To further mimic the neurotoxic niche in AD brain, we treated iPSC-derived neurons with Aβ42 oligomer (AβO). BFCNs are less sensitive to AβO induced tau phosphorylation and expression than cortical glutamatergic neurons. However, AβO could trigger apoptosis in both AD-cortical glutamatergic neurons and AD-BFCNs. In addition, AD iPSC-derived BFCNs and cortical glutamatergic neurons exhibited distinct electrophysiological firing patterns and elicited different responses to AβO treatment. These observations revealed that subtype-specific neurons display distinct neuropathological changes during the progression of AD, which might help to understand AD pathogenesis at the cellular level.

The COVID-19 pandemic has caused a global health crisis and significant social economic burden. While most individuals experience mild or non-specific symptoms, elderly individuals are at a higher risk of developing severe symptoms and life-threatening complications. Exploring the key factors associated with clinical severity highlights that key characteristics of aging, such as cellular senescence, immune dysregulation, metabolic alterations, and impaired regenerative potential, contribute to disruption of tissue homeostasis of the lung and worse clinical outcome. Senolytic and senomorphic drugs, which are anti-aging treatments designed to eliminate senescent cells or decrease the associated phenotypes, have shown promise in alleviating age-related dysfunctions and offer a novel approach to treating diseases that share certain aspects of underlying mechanisms with aging, including COVID-19. This review summarizes the current understanding of aging in COVID-19 progression, and highlights recent findings on anti-aging drugs that could be repurposed for COVID-19 treatment to complement existing therapies.