生理学报最新文献

{"title":"[From hematopoietic suppression to therapy resistance: the dual outcomes of leukemia-induced remodeling of the bone marrow vascular microenvironment].","authors":"Liang-Gui Huang, Yi-Jun Zhao, Jun-Zhu Chen, Lin-Jia Jiang","doi":"10.13294/j.aps.2026.0080","DOIUrl":"https://doi.org/10.13294/j.aps.2026.0080","url":null,"abstract":"<p><p>The bone marrow vascular microenvironment is primarily composed of endothelial cells (ECs) and mesenchymal stem/stromal cells (MSCs), which maintain hematopoietic homeostasis by regulating the quiescence, activation, proliferation, and differentiation of hematopoietic stem cells (HSCs). During leukemogenesis and disease progression, malignant cells remodel the vascular microenvironment, leading to aberrant vascular architecture, disruption of endothelial barrier integrity, phenotypic conversion of MSCs toward a pro-inflammatory/pro-survival state, and the dismantling of normal signaling networks among ECs, MSCs, and HSCs, alongside the establishment of aberrant communication axes. These alterations, on one hand, disrupt the supportive HSC niche, resulting in bone marrow failure-associated pancytopenia. On the other hand, the remodeled vascular microenvironment transforms into a sanctuary that promotes leukemia cell proliferation, migration, and drug resistance, ultimately driving disease relapse and poor prognosis. This review systematically elucidates the mechanisms underlying leukemia-induced remodeling of the bone marrow vascular microenvironment and, based on these findings, summarizes emerging therapeutic strategies targeting the vascular microenvironment, aiming to provide a theoretical foundation and translational directions for overcoming therapy resistance in leukemia.</p>","PeriodicalId":7134,"journal":{"name":"生理学报","volume":"78 4","pages":"815-824"},"PeriodicalIF":0.0,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148863225","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sperm-associated antigen 6 (SPAG6): roles in human cancer and other diseases.","authors":"Qing-Lin Li, Peng-Zhan Zhou, Zhi-Yi Lv, Han-Qi Liu, Kang Liu, Yang Mei","doi":"10.13294/j.aps.2026.0062","DOIUrl":"https://doi.org/10.13294/j.aps.2026.0062","url":null,"abstract":"<p><p>Emerging evidence indicates that sperm-associated antigen 6 (SPAG6), a protein initially characterized for its role in ciliogenesis and spermatogenesis, plays critical roles not only in the genital system but also in the nervous, immune, and hematopoietic systems. More recently, SPAG6 has been increasingly implicated in cancer progression and treatment. In this review, we systematically summarize the molecular characterization of SPAG6 and delineate its functional roles and pathophysiological mechanisms across multiple organ systems. We also review its therapeutic relevance in cancer management, especially in hematopoietic malignancy. Notably, SPAG6 was found to be aberrantly overexpressed in clinical myelodysplastic syndrome (MDS) patients and promote the proliferation of MDS-L cells. While functional discrepancies of SPAG6 across experimental models warrant further in-depth exploration, elucidating its mechanisms in disease pathogenesis could offer valuable insights for developing targeted therapies for human diseases.</p>","PeriodicalId":7134,"journal":{"name":"生理学报","volume":"78 4","pages":"838-850"},"PeriodicalIF":0.0,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148863249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Erythroid differentiation: regulatory mechanisms and translational applications].","authors":"Shuo Zhou, Xin-Ying Zhao, Yue-Hua Liu, Yue-Lin Deng, Na Li, Xiaofei Gao, Hsiang-Ying Lee","doi":"10.13294/j.aps.2026.0079","DOIUrl":"https://doi.org/10.13294/j.aps.2026.0079","url":null,"abstract":"<p><p>Erythrocytes support tissue oxygen-dependent energy metabolism by enabling oxygen transport and are essential for maintaining metabolic homeostasis. Their differentiation and development are orchestrated by multilayered regulatory networks that play a decisive role in sustaining hematopoietic homeostasis. Although key regulators and signaling pathways governing erythropoiesis have been extensively characterized, how these mechanisms are integrated across developmental transitions, stress responses, and disease states remains incompletely understood. Here, we provide a comprehensive overview of the structural basis, developmental programs, and regulatory logic of erythropoiesis. We first summarize the structural features of erythrocytes, with a focus on the membrane skeleton and its spatiotemporal assembly and relevant regulatory mechanisms. We then outline the developmental trajectories and stage-specific characteristics of erythropoiesis under both steady-state and stress conditions. Building on this framework, we integrate current knowledge on the multilayered regulatory networks governing erythropoiesis, including transcriptional control, epigenetic regulation, metabolic reprogramming, and signals from the hematopoietic microenvironment. Furthermore, using representative erythrocyte-related disorders as a lens, we discuss how dysregulation of these pathways contributes to disease pathogenesis. Finally, we highlight recent advances and key challenges in the translational applications of erythrocytes, including <i>in vitro</i> generation, drug delivery, immunomodulation, and regenerative medicine. This review aims to establish an integrated conceptual framework for erythroid development and to provide insights for future mechanistic studies and clinical translation.</p>","PeriodicalId":7134,"journal":{"name":"生理学报","volume":"78 4","pages":"762-788"},"PeriodicalIF":0.0,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148863260","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[NAD kinases (NADKs) family proteins: Advances in metabolic regulation mechanisms and disease associations].","authors":"Si-Yu Cheng, Hong-Yu Pan, Di Wang, Xu Jin, Qi-Mei Cheng, Cheng-Jie Gao, Li-Hong Shi","doi":"10.13294/j.aps.2026.0072","DOIUrl":"https://doi.org/10.13294/j.aps.2026.0072","url":null,"abstract":"<p><p>Nicotinamide adenine dinucleotide [NAD(H), consisting of its oxidized form NAD⁺ and reduced form NADH] and nicotinamide adenine dinucleotide phosphate [NADP(H), consisting of its oxidized form NADP⁺ and reduced form NADPH] are core molecular pair governing metabolic regulation, which exert central functions in modulating cellular energy metabolism, redox homeostasis and biosynthesis. The imbalance of intracellular ratio of NAD(H) to NADP(H) can lead to serious pathophysiological consequences and trigger a wide spectrum of diseases. NAD kinases (NADKs), the sole enzymes that phosphorylate NAD(H) to NADP(H), therefore sit at the hub of NAD(H)/NADP(H) balance control. Because NADP⁺ cannot cross subcellular membranes, eukaryotic NADKs are classified into two isoforms: cytosolic NADK1 and mitochondrial NADK2. The catalytic activity of NADKs is regulated at the transcriptional and post-translational modification levels, and aberrant expression or dysfunction of NADKs is closely linked to the initiation and progression of numerous diseases. Targeted intervention strategies against NADKs thus represent a promising therapeutic avenue for the clinical treatments of tumors, metabolic disorders, and other related diseases.</p>","PeriodicalId":7134,"journal":{"name":"生理学报","volume":"78 4","pages":"867-876"},"PeriodicalIF":0.0,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148863172","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Metabolic reprogramming and the related therapeutic strategies for leukemia stem cells].","authors":"Si-Miao Wu, Rong Yin, Hao-Jian Zhang","doi":"10.13294/j.aps.2026.0082","DOIUrl":"https://doi.org/10.13294/j.aps.2026.0082","url":null,"abstract":"<p><p>Metabolic reprogramming lies at the core of the malignant features of acute myeloid leukemia stem cells (LSCs), and represents a critical window for selective targeting. Unlike quiescent hematopoietic stem cells (HSCs) that mainly rely on glycolysis to maintain low levels of reactive oxygen species, LSCs acquire remarkable metabolic plasticity during malignant transformation, enabling them to simultaneously utilize glycolysis and oxidative phosphorylation (OXPHOS) to meet biosynthetic demands and establish therapeutic resistance. These divergences between LSCs and HSCs are rooted in profound regulatory differences in terms of energy metabolism pathways, mitochondrial functional regulation and metabolic-epigenetic crosstalk networks. This review comprehensively summarizes the molecular basis of metabolic regulation in HSCs and LSCs, discusses the regulatory mechanisms of metabolic reprogramming in LSCs, and explores precise therapeutic strategies targeting the specific metabolic programs of LSCs, thereby providing new insights for overcoming therapeutic resistance in leukemia.</p>","PeriodicalId":7134,"journal":{"name":"生理学报","volume":"78 4","pages":"825-837"},"PeriodicalIF":0.0,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148863181","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Progress on the physiological functions and clinical applications of red blood cell-derived extracellular vesicles].","authors":"Hong-Yu Pan, Si-Yu Cheng, Jing-Wei Wang, Le-Xuan Lin, Xin-Yu Li, Cheng-Jie Gao, Li-Hong Shi","doi":"10.13294/j.aps.2026.0068","DOIUrl":"https://doi.org/10.13294/j.aps.2026.0068","url":null,"abstract":"<p><p>Red blood cell-derived extracellular vesicles (RBC-EVs) are one of the most abundant types of extracellular vesicles (EVs) in the blood, playing a crucial role in intercellular communication, disease progression, and medical applications. The structure of RBC-EVs differs from that of red blood cells (RBCs), characterized by phosphatidylserine externalization, reduced membrane proteins, and encapsulation of bioactive molecules such as hemoglobin and miRNAs. RBC-EVs primarily exist as microvesicles and exosomes, which are generated through membrane budding and the multivesicular bodies pathway, respectively. Their clearance <i>in vivo</i> mainly relies on phagocytosis by hepatic Kupffer cells. Physiologically, RBC-EVs maintain the normal physiological functions of RBCs by removing damaged and senescent signals from the RBC membrane, regulate organismal homeostasis through participation in nitric oxide balance and anticoagulant processes, and also engage in immune regulation and exert certain antiviral effects. Additionally, they serve as intercellular information carriers to function in various diseases. Endowed with advantages such as high biocompatibility and low immunogenicity, RBC-EVs have demonstrated enormous clinical application potential as carriers for small-molecule drugs (e.g., nucleic acids) in fields including hematological diseases, liver diseases, and cancer. This review systematically summarizes the composition and structure, biogenesis and clearance mechanisms, main physiological functions, clinical applications, and future prospects of RBC-EVs.</p>","PeriodicalId":7134,"journal":{"name":"生理学报","volume":"78 4","pages":"789-802"},"PeriodicalIF":0.0,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148863184","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Research progress on sphingolipid metabolic remodeling and targeted therapy in acute myeloid leukemia].","authors":"Quan Wu, Hui Zeng","doi":"10.13294/j.aps.2026.0085","DOIUrl":"https://doi.org/10.13294/j.aps.2026.0085","url":null,"abstract":"<p><p>Sphingolipids are a class of bioactive lipids that serve as both structural components of cellular membranes and key regulators of signal transduction. Their metabolic derivatives, including ceramide (Cer), sphingosine (Sph), and sphingosine-1-phosphate (S1P), play important regulatory roles in diverse biological processes, such as cell proliferation, apoptosis, autophagy, and stress responses. In selected acute myeloid leukemia (AML) models, sphingolipid metabolic remodeling characterized by disrupted Cer homeostasis has been observed and is closely associated with AML cell survival, therapeutic resistance, and disease relapse. In this review, we focus on the key processes involved in sphingolipid metabolic remodeling in AML, discuss their roles in sustaining AML cell survival and mediating drug resistance, and summarize potential therapeutic strategies targeting critical nodes of sphingolipid metabolism.</p>","PeriodicalId":7134,"journal":{"name":"生理学报","volume":"78 4","pages":"803-814"},"PeriodicalIF":0.0,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148863235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Applications and advances of single-cell omics technologies in hematopoietic stem cell research].","authors":"Yi-Yang Zhang, Fang Dong","doi":"10.13294/j.aps.2026.0061","DOIUrl":"https://doi.org/10.13294/j.aps.2026.0061","url":null,"abstract":"<p><p>Stem cells, as a class of cells possessing self-renewal and multipotent differentiation potential, exhibit functional diversity influenced by both intrinsic regulatory networks and external microenvironments. Traditional population-level research methods struggle to precisely resolve cellular heterogeneity, thereby limiting in-depth understanding of stem cell biology. Recent breakthroughs in single-cell analysis technologies have opened new avenues for detailed observation at the cellular level. This review focuses on hematopoietic stem cells as a primary example, summarizing the principles and advancements of single-cell transcriptomics, epigenomics, proteomics, metabolomics, spatialomics, and multi-omics integration analysis. It explores their applications in revealing stem cell heterogeneity, differentiation pathways, and state regulation mechanisms, while also outlining future directions for single-cell technologies in stem cell research.</p>","PeriodicalId":7134,"journal":{"name":"生理学报","volume":"78 4","pages":"741-761"},"PeriodicalIF":0.0,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148863191","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Diabetes-driven hematopoietic remodeling and metabolic memory].","authors":"Yi-Wen Wu, Fang Dong, Xiao-Xia Hu","doi":"10.13294/j.aps.2026.0076","DOIUrl":"https://doi.org/10.13294/j.aps.2026.0076","url":null,"abstract":"<p><p>Diabetes mellitus is a metabolic disorder characterized by chronic hyperglycemia and is accompanied by a range of complications affecting the cardiovascular system, kidneys, retina, and nervous system. In the context of diabetes, the bone marrow (BM) and hematopoietic stem and progenitor cells (HSPCs) are not only targets of metabolic dysregulation, but also play an active role in driving chronic inflammation and tissue damage. Prolonged hyperglycemia markedly disrupts HSPC bone marrow niche homeostasis, leading to decreased HSPC numbers, impaired mobilization, and biased differentiation. As a result, the hematopoietic system shifts from supporting tissue repair and immune homeostasis to driving pro-inflammatory hematopoiesis. Diabetes induces metabolic reprogramming and epigenetic remodeling in HSPCs, as well as in supportive cells within the BM niche. Aberrant metabolic states interact with epigenetic regulation to reshape transcriptional programs in HSPCs, thereby establishing a stable inflammatory hematopoietic phenotype. In addition, diabetes-associated trained immunity enables HSPCs to acquire pro-inflammatory memory and transmit this bias to their myeloid progeny, providing a mechanistic link between metabolic memory and chronic inflammation. This review systematically summarizes abnormalities in the number and function of hematopoietic cells under diabetic conditions, as well as the roles of metabolic reprogramming and epigenetic regulation in hematopoietic imbalance. It focuses on recent progress in diabetes-associated hematopoietic remodeling and metabolic memory, aiming to provide a hematopoietic perspective for understanding the pathophysiological processes underlying diabetes-induced multi-organ alterations and to offer a reference for exploring potential hematopoietic intervention targets for diabetic complications.</p>","PeriodicalId":7134,"journal":{"name":"生理学报","volume":"78 4","pages":"889-903"},"PeriodicalIF":0.0,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148863183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[CHAF1A sustains hematopoietic stem cell stemness by enhancing the activity of the NF-Y transcription factor family].","authors":"Jin Liu, Meng-Du Xiao, Wan-Ling You, Yue Sheng, Hu Wang","doi":"10.13294/j.aps.2026.0069","DOIUrl":"https://doi.org/10.13294/j.aps.2026.0069","url":null,"abstract":"<p><p>This study aimed to investigate the regulatory role and underlying molecular mechanisms of chromatin assembly factor 1 subunit CHAF1A in the function of hematopoietic stem cells (HSCs) in adult mice. A hematopoietic-specific <i>Chaf1a</i> knockout mouse model was established, and multiple approaches including flow cytometry, RNA-seq, ATAC-seq, and HINT-ATAC were integrated for multidimensional systematic analysis. CHAF1A depletion led to a pronounced reduction in peripheral blood platelet count. In the bone marrow, the number of LSK (lineage^- Sca-1⁺ c-Kit⁺) cells and HSCs was markedly decreased, while no significant difference was observed in the number of hematopoietic progenitor cells (common myeloid progenitors, megakaryocyte-erythroid progenitors and granulocyte-monocyte progenitors) in the CHAF1A-deficient group. Additionally, no significant differences were observed in HSC cell cycle distribution or apoptosis. RNA-seq identified 904 upregulated and 781 downregulated genes in CHAF1A-deficient HSCs. Gene set enrichment analysis (GSEA) showed that stemness-related genes were significantly enriched in wild-type HSCs, while differentiation-related genes were significantly enriched in CHAF1A-deficient HSCs. ATAC-seq revealed reduced chromatin accessibility at the transcription start site (TSS) regions of HSCs in the CHAF1A-deficient group. HINT-ATAC analysis further showed that the activity of NF-Y family transcription factors was significantly higher in wild-type HSCs than in CHAF1A-deficient HSCs, while the activities of CEBPA and CEBPD were significantly higher in CHAF1A-deficient HSCs. Collectively, these results suggest that CHAF1A is essential for the maintenance of adult mouse HSCs. Specifically, CHAF1A enhances the activity of NF-Y family transcription factors to sustain HSC stemness and inhibits the function of CEBP family transcription factors to block HSC differentiation. Its regulatory mechanism involves the coordinated regulation of chromatin accessibility and transcription factor activity.</p>","PeriodicalId":7134,"journal":{"name":"生理学报","volume":"78 4","pages":"931-942"},"PeriodicalIF":0.0,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148863258","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}