The skeleton is an important structural and metabolic organ in human body, while aging is the physiological basis for degenerative skeletal diseases. China has the largest aging population in the world and faces great challenges in preventing and managing diseases related to skeletal aging. To address these challenges, the Aging China Biomarkers Consortium (ABC) has reached an expert consensus on biomarkers of skeletal aging by synthesizing the literature and insights from scientists and clinicians. The consensus provides a comprehensive assessment of biomarkers associated with skeletal aging and proposes a systematic framework that categorizes biomarkers into three dimensions, namely, functional, structural, and humoral dimensions. Within each dimension, the ABC recommended clinical and evidential research-based biomarkers for physiological aging and degenerative pathologies of the skeleton. This expert consensus aims to lay the foundation for future studies to assess the prediction, diagnosis, early warning, and treatment of diseases associated with skeletal aging, with the ultimate goal of improving the skeletal health of elderly populations in China and around the world.

Aging is a complex and heterogeneous process, raising important questions about how aging is differently impacted by underlying genetics and external factors. Recently, migrasomes, newly discovered organelles, have been identified to play important roles in various physiological and pathological processes by facilitating cell-to-cell communication. Thus far, their involvement in cellular senescence and aging remains largely unexplored. In this study, we aimed to investigate how migrasomes impact on cellular aging by leveraging multiple cellular senescence models, including replicatively senescent (RS), pathologically senescent and stress-induced senescent human mesenchymal stem cells (hMSCs), as well as RS human primary fibroblasts. In all cellular aging models, we detected an enhanced formation of migrasomes. Notably, migrasomes in senescent cells exhibited an accumulation of numerous aging hallmarks, such as dysfunctional mitochondria, endogenous retroviruses, and senescence-associated pro-inflammatory cytokines. Furthermore, we discovered that migrasomes derived from senescent cells can be taken up by young cells, thereby transferring aging signals and subsequently causing premature senescence phenotypes in recipient cells. Mechanistically, we found that treatment with migrasomes derived from senescent cells activated the innate immune response. Thus, our study sheds light on a pivotal role of migrasomes in mediating the contagiousness of aging.

The pathogenesis of several kidney diseases results in the eventual destruction of the renal tubular system, which can progress to end-stage renal disease. Previous studies have demonstrated the involvement of a population of SOX9-positive cells in kidney regeneration and repair process following kidney injury. However, the ability of these cells to autonomously generate kidney organoids has never been investigated. Here, we isolated SOX9⁺ kidney progenitor cells (KPCs) from both mice and humans and tested their differentiation potential in vitro. The data showed that the human SOX9⁺ KPC could self-assemble into organoids with kidney-like morphology. We also used single-cell RNA sequencing to characterize the organoid cell populations and identified four distinct types of renal tubular cells. Compared to the induced pluripotent stem cell-derived kidney organoids, KPC demonstrated more tubular differentiation potential but failed to differentiate into glomerular cells. KPC-derived organoid formation involved the expression of genes related to metanephric development and followed a similar mechanism to renal injury repair in acute kidney injury patients. Altogether, our study provided a potentially useful approach to generating kidney tubular organoids for future application.

As the most prevalent type of alternative splicing in animal cells, exon skipping plays an important role in expanding the diversity of transcriptome and proteome, thereby participating in the regulation of diverse physiological and pathological processes such as development, aging, and cancer. Cellular senescence serving as an anti-cancer mechanism could also contribute to individual aging. Although the dynamic changes of exon skipping during cellular senescence were revealed, its biological consequence and upstream regulator remain poorly understood. Here, by using human foreskin fibroblasts (HFF) replicative senescence as a model, we discovered that splicing factor PTBP1 was an important contributor for global exon skipping events during senescence. Down-regulated expression of PTBP1 induced senescence-associated phenotypes and related mitochondrial functional changes. Mechanistically, PTBP1 binds to the third exon of mitochondrial complex I subunit coding gene NDUFV3 and protects the exon from skipping. We further confirmed that exon skipping of NDUFV3 correlates with and partially contributes to cellular senescence and related mitochondrial functional changes upon PTBP1 knockdown. Together, we revealed for the first time that mitochondrial-related gene NDUFV3 is a new downstream target for PTBP1-regulated exon skipping to mediate cellular senescence and mitochondrial functional changes.

Pharyngeal pouches, which are endodermal outpockets that segment the pharyngeal arches, play a crucial role in the development of craniofacial skeletons in vertebrate embryos. Our previous study successfully identified pharyngeal pouch progenitors (PPPs) in zebrafish embryos and emphasized the significance of BMP2b signaling in their specification. However, the specific mechanism by which these progenitors originate from endodermal cells remains largely unknown. Here we found that the pharmacological activation of Wnt signaling pathway disrupts the emergence of PPPs and subsequently hinders the formation of pharyngeal pouches. Moreover, we have identified the expression of tmem88a and tmem88b (collectively known as tmem88a/b) in PPPs during the early-somite stages. Furthermore, the deficiency of tmem88a/b leads to an excessive accumulation of β-catenin in both the cytoplasm and nucleus of endodermal cells that are intended to differentiate into PPPs. Importantly, suppressing the hyperactivation of Wnt/β-catenin signaling through pharmacological treatment, the defects in PPP specification in tmem88a/b^−/− mutants are successfully rescued. In summary, our findings establish a clear connection between the specification of PPPs and the regulation of Wnt signaling mediated by Tmem88. These results underscore the pivotal role of Tmem88 in the development of pharyngeal pouches.

Glioma stem cells (GSCs) in the hypoxic niches contribute to tumor initiation, progression, and recurrence in glioblastoma (GBM). Metabolic pathways are altered in GSCs under hypoxia, but the mechanism underlying the altered one-carbon metabolism in GSCs by hypoxia is largely unknown. Here, we report that hypoxia induces down-regulation of DHFR as well as up-regulation of MAT2A in GBM tumorsphere cells, and confers them the ability of cell proliferation that is independent of exogenous folate. Importantly, short-term inhibition of the methionine cycle or exposure to the MAT2A inhibitor is sufficient to cripple the tumor-initiating capability of GBM tumorsphere cells. Therefore, we present a novel perspective on how hypoxia alters the pattern of one-carbon metabolism in GBM tumorsphere cells and provide evidence that restriction of methionine intake or targeting MAT2A inhibits the tumorigenicity of GBM tumorsphere cells.

3D bioprinting emerges as a critical tool in biofabricating functional 3D tissue or organ equivalents for regenerative medicine. Bioprinting techniques have been making strides in integrating automation, customization, and digitalization in coping with diverse tissue engineering scenarios. The convergence of robotic arm-based 3D bioprinting techniques, especially in situ 3D bioprinting, is a versatile toolbox in the industrial field, promising for biomedical application and clinical research. In this review, we first introduce conceptualized modalities of robotic arm-based bioprinting from a mechanical perspective, which involves configurative categories of current robot arms regarding conventional bioprinting strategies. Recent advances in robotic arm-based bioprinting in tissue engineering have been summarized in distinct tissues and organs. Ultimately, we systematically discuss relative advantages, disadvantages, challenges, and future perspectives from bench to bedside for biomedical application.

Recurrent spontaneous abortion (RSA) affects 2%–5% of couples worldwide and remains a subject of debate regarding the effectiveness of lymphocyte immunotherapy (LIT) due to limited retrospective studies. We conducted a comprehensive Bayesian analysis to assess the impact of LIT on RSA. Using data from the Shenzhen Maternity and Child Healthcare Hospital (2001–2020, n = 2316), a Bayesian generalized linear model with predictive projection feature selection was employed. Our analysis revealed a significant improvement in live birth rates for RSA patients undergoing LIT. Notably, LIT had a greater impact compared to the other 85 factors considered. To mitigate research bias, we conducted a Bayesian meta-analysis combining our dataset with 19 previously reported studies (1985–2021, n = 4246). Additionally, we developed an empirical model high-lighting the four key factors, which are the LIT result, age, paternal blood type, and anticardiolipin antibody. Younger age (19–27), paternal blood type B, and a positive anticardiolipin antibody (IgM) were associated with better therapeutic outcomes in LIT for RSA. These findings aid clinicians in identifying suitable candidates for LIT and improving treatment outcomes.

Mitochondrial transplantation (MT) is a promising therapeutic strategy that involves introducing healthy mitochondria into damaged tissues to restore cellular function. This approach has shown promise in treating cardiac diseases, such as ischemia-reperfusion injury, myocardial infarction, and heart failure, where mitochondrial dysfunction plays a crucial role. Transplanting healthy mitochondria into affected cardiac tissue has resulted in improved cardiac function, reduced infract size, and enhanced cell survival in preclinical studies. Beyond cardiac applications, MT is also being explored for its potential to address various noncardiac diseases, including stroke, infertility, and genetic mitochondrial disorders. Ongoing research focused on refining techniques for mitochondrial isolation, preservation, and targeted delivery is bolstering the prospects of MT as a clinical therapy. As the scientific community gains a deeper understanding of mitochondrial dynamics and pathology, the development of MT as a clinical therapy holds significant promise. This review provides an overview of recent research on MT and discusses the methodologies involved, including sources, isolation, delivery, internalization, and distribution of mitochondria. Additionally, it explores the effects of MT and potential mechanisms in cardiac diseases, as well as non-cardiac diseases. Future prospects for MT are also discussed.

Synthetic organ models such as organoids and organ-on-a-chip have been receiving recognition from administrative agencies. Despite the proven success of organoids in predicting drug efficacy on laboratory scales, their translational advances have not fully satisfied the expectations for both clinical implementation and commercial applications. The transition from laboratory settings to clinical applications continues to encounter challenges. Employing engineering methodologies to facilitate the bridging of this gap for organoids represents one of the key directions for future advancement. The main measures to bridge the gap include environmental and phenotypic recapitulation, 3D patterning, matrix engineering, and multi-modality information acquisition and processing. Pilot whole-process clinical/pharmaceutical applications with fast and standardized organoid models will continuously offer convincing frontline optimization clues and driving forces to the organoid community, which is a promising path to translational organoid technologies.

The advent of single-cell sequencing techniques has not only revolutionized the investigation of biological processes but also significantly contributed to unraveling cellular heterogeneity at unprecedented levels. Among the various methods, single-cell transcriptome sequencing stands out as the best established, and has been employed in exploring many physiological and pathological activities. The recently developed single-cell epigenetic sequencing techniques, especially chromatin accessibility sequencing, have further deepened our understanding of gene regulatory networks. In this review, we summarize the recent breakthroughs in single-cell transcriptome and chromatin accessibility sequencing methodologies. Additionally, we describe current bioinformatic strategies to integrate data obtained through these single-cell sequencing methods and highlight the application of this analysis strategy on a deeper understanding of tumorigenesis and tumor progression. Finally, we also discuss the challenges and anticipated developments in this field.

Awareness of estrogen’s effects on health is broadening rapidly. The effects of long-term high levels of estrogen on the body involve multiple organs. Here, we used both single-cell chromatin accessibility and RNA sequencing data to analyze the potential effect of estrogen on major organs. The integrated cell map enabled in-depth dissection and comparison of molecular dynamics, cell-type compositions, and cellular heterogeneity across multiple tissues and organs under estrogen stimulation. We also inferred pseudotime cell trajectories and cell–cell communications to uncover key molecular signatures underlying their cellular processes in major organs in response to estrogen. For example, estrogen could induce the differentiation of IFIT3⁺ neutrophils into S100A9⁺ neutrophils involved in the function of endosome-to-lysosome transport and the multivesicular body sorting pathway in liver tissues. Furthermore, through integration with human genome-wide association study data, we further identified a subset of risk genes during disease development that were induced by estrogen, such as AKT1 (related to endometrial cancer), CCND1 (related to breast cancer), HSPH1 (related to colorectal cancer), and COVID-19 and asthma-related risk genes. Our work uncovers the impact of estrogen on the major organs, constitutes a useful resource, and reveals the contribution and mechanism of estrogen to related diseases.