Experimental hematology最新文献

{"title":"Honoring giants in hematopoietic stem and progenitor cell biology","authors":"Louise E. Purton","doi":"10.1016/j.exphem.2025.105263","DOIUrl":"10.1016/j.exphem.2025.105263","url":null,"abstract":"","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":"151 ","pages":"Article 105263"},"PeriodicalIF":2.1,"publicationDate":"2025-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145267175","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondrial Retention and Autophagy Dysregulation Drive Oxidative Stress in Sickle Cell Disease Erythrocytes.","authors":"Jagadeesh Ramasamy, Prasanth Kumar Punathil Kannan, Sugasini Dhavamani, Savitha Palanimuthu, Robert Molokie, Angela Rivers","doi":"10.1016/j.exphem.2025.105269","DOIUrl":"https://doi.org/10.1016/j.exphem.2025.105269","url":null,"abstract":"<p><p>Sickle cell disease (SCD) is an inherited blood disorder caused by a mutation in the beta-globin gene, leading to hemoglobin polymerization under low oxygen conditions. This results in sickle-shaped red blood cells (Erythrocytes), hemolysis, severe acute and chronic pain, and shortened erythrocyte lifespan. The severity of disease in SCD is linked to the type of hemoglobin mutation, with HbSS causing more frequent and severe than HbSC. We previously identified mitochondrial retention and excessive reactive oxygen species (ROS) production in SCD erythrocytes. Here, we report that SCD patients with the HbSS exhibit significantly higher erythrocyte mitochondrial retention and ROS levels than those with the HbSC. Mitochondrial retention positively correlates with serum bilirubin and LDH, particularly in hydroxyurea-naïve patients. Gene expression analysis using a human autophagy array revealed upregulation of SNCA, GABARAP, GABRAPL2, MAP1LC3B, and CTSB in erythrocyte precursor cells from SCD patients experiencing severe pain. Immunoblot analyses further confirmed accumulation of GABARAP, GABARAPL1, GABARAPL2, cathepsin B, and synuclein-alpha in circulating erythrocytes and plasma from SCD patients compared to controls. Our findings suggest a potential link between dysregulated autophagy proteins and erythrocyte mitochondrial retention in SCD patients, opening new avenues for therapeutic interventions targeting these proteins to mitigate SCD pathogenesis. TEASER ABSTRACT: Sickle cell disease (SCD) causes painful crises due to hemoglobin mutations, with HbSS patients experiencing more severe symptoms than HbSC. We show that HbSS erythrocytes retain more mitochondria and produce higher ROS levels, correlating with bilirubin and LDH, especially in hydroxyurea-naïve individuals. Autophagy-related genes and proteins SNCA, GABARAPs, CTSB are upregulated in erythrocyte precursors and plasma of SCD patients with severe pain. These findings suggest a potential link between dysregulated autophagy proteins and mitochondrial retention in SCD patients, opening new avenues for therapeutic interventions.</p>","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":" ","pages":"105269"},"PeriodicalIF":2.1,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145228367","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Shaping the future of Experimental Hematology: an interview with Dr. Toshio Suda","authors":"Keisuke Ito","doi":"10.1016/j.exphem.2025.104879","DOIUrl":"10.1016/j.exphem.2025.104879","url":null,"abstract":"","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":"150 ","pages":"Article 104879"},"PeriodicalIF":2.1,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144948167","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Special Issue: RNA and Hematology","authors":"Carl Walkley","doi":"10.1016/j.exphem.2025.105244","DOIUrl":"10.1016/j.exphem.2025.105244","url":null,"abstract":"","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":"150 ","pages":"Article 105244"},"PeriodicalIF":2.1,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144948170","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IFC Editorial Board","authors":"","doi":"10.1016/S0301-472X(25)00543-0","DOIUrl":"10.1016/S0301-472X(25)00543-0","url":null,"abstract":"","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":"150 ","pages":"Article 105254"},"PeriodicalIF":2.1,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145216514","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FAM210B regulates iron homeostasis and sex-specific responses in stress erythropoiesis","authors":"Mark Perfetto ,&nbsp;Muhammad Ishfaq ,&nbsp;Aiden Mohideen ,&nbsp;Catherine M. Rondelli ,&nbsp;Samantha Gillis ,&nbsp;Jesus Tejero ,&nbsp;Amber N. Stratman ,&nbsp;Rebecca B. Riggins ,&nbsp;Yvette Y. Yien","doi":"10.1016/j.exphem.2025.104797","DOIUrl":"10.1016/j.exphem.2025.104797","url":null,"abstract":"<div><div>Iron is required for redox homeostasis but poses toxicity risks due to its redox activity. Erythropoiesis hence requires tight regulation of iron utilization for hemoglobin synthesis. The requirement for iron in erythropoiesis has necessitated the evolution of mechanisms to handle the iron required for hemoglobinization. FAM210B was identified as a regulator of mitochondrial iron import and heme synthesis in erythroid cell culture and zebrafish models. Here, we demonstrate that although FAM210B is required for erythroid differentiation and heme synthesis under standard cell culture conditions, holotransferrin supplementation was sufficient to chemically complement the iron-deficient phenotype. To investigate the role of FAM210B in erythropoiesis, we used knockout mice. Although <em>Fam210b^−/−</em> mice were viable and did not exhibit overt erythropoietic defects in the bone marrow, the male mice exhibited an increase in serum transferrin, suggesting sex-specific alterations in systemic iron sensing. On phlebotomy-induced stress erythropoiesis, <em>Fam210b^−/−</em> mice exhibited differences in serum transferrin levels, and more starkly, had markedly smaller spleens, indicating defects in stress response. <em>Fam210b^−/−</em> males had defects in neutrophil and monocyte numbers, as well as decreased erythroid progenitor numbers during erythropoietic stress. Together, our findings show that <em>Fam210b</em> plays a key role in the splenic response to erythropoietic stress. Our findings reveal a critical role for FAM210B in mediating splenic stress erythropoiesis and suggest it may act as a sex-specific regulator, potentially linked to androgen signaling.</div></div>","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":"150 ","pages":"Article 104797"},"PeriodicalIF":2.1,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143991599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A new anchor point for gut microbiome to regulate complications of allogeneic hematopoietic stem cell transplantation: oxidative stress","authors":"Wenxuan Bai ,&nbsp;Tiebin Jiang ,&nbsp;Lanlan Tang ,&nbsp;Chuhan Shao ,&nbsp;Mamingxi Wei ,&nbsp;Zisai Wang ,&nbsp;Mingyi Zhao","doi":"10.1016/j.exphem.2025.104833","DOIUrl":"10.1016/j.exphem.2025.104833","url":null,"abstract":"<div><div>Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a cure for many malignant hematologic and metabolic diseases, whose complications are an unignorable cause of long-term prognosis. Pretreatment chemoradiotherapy administered before and after transplantation alters the state of the bone marrow hematopoietic microenvironment. Under the stress of hematopoietic injury, a large number of hematopoietic stem cells (HSCs) proliferate and differentiate, producing large amounts of reactive oxygen species (ROS). In addition, the chemotherapeutic pretreatment drugs also cause oxidative stress (OS) themselves, which can indirectly exacerbate OS of the bone marrow microenvironment. The bone marrow hematopoietic microenvironment and local OS affect the development of infections, relapse, graft-versus-host disease (GVHD), poor graft function (PGF), persistent thrombocytopenia (PT), chronic fatigue syndrome (CFS), bronchiolitis obliterans syndrome (BOS), and transplant-associated thrombotic microangiopathy (TA-TMA). Recent studies have demonstrated that the gut microbiome (GM) and its metabolites such as short-chain fatty acids (SCFAs), secondary bile acids, trimethylamine (TMA) and signaling molecules such as H₂S and NO can enter the bloodstream through the intestinal epithelium and reach all parts of the body. This review describes the impact of OS on the development of allo-HSCT complications. In this article, we will elucidate the mechanism of OS on allo-HSCT complications, summarize the interaction between GM and OS in the body, and highlight the role of GM regulation of OS in allo-HSCT complications to offer new strategies for the prevention and treatment of allo-HSCT complications.</div></div>","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":"150 ","pages":"Article 104833"},"PeriodicalIF":2.1,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144309736","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neutrophil death-more than meets the eye.","authors":"Alan Y Hsu, Qingxiang Huang, Fei Liu, Arumugam Balasubramanian, Hongbo R Luo","doi":"10.1016/j.exphem.2025.104857","DOIUrl":"10.1016/j.exphem.2025.104857","url":null,"abstract":"<p><p>Neutrophils play an indispensable role in the innate immune system as the body's first line of defense against pathogens. These highly specialized cells are rapidly recruited to infection sites, where they execute a variety of critical functions essential for pathogen clearance. These functions include phagocytosis, degranulation, the release of antimicrobial peptides and reactive oxygen species (ROS), as well as the formation of neutrophil extracellular traps (NETs), which serve to directly neutralize pathogens or restrict their spread. Despite their abundance-accounting for 40%-70% of total white blood cells in human circulation, neutrophils have a relatively short lifespan. To maintain immune homeostasis, approximately 1 billion neutrophils per kilogram of body weight are produced and cleared each day, a highly regulated and energy-intensive process. Neutrophil death is a highly heterogeneous process, with neutrophils undergoing different forms of cell death depending on the stimuli, signaling, and microenvironment. Even during aging or cell death, neutrophils continue to exert significant effects on the immune landscape. In this review, we discuss the dynamics of neutrophil turnover during homeostasis and inflammation, the diversity of mechanisms governing their death, and the multifaceted roles of neutrophils in modulating the immune environment both during and after their demise.</p>","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":" ","pages":"104857"},"PeriodicalIF":2.1,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12376072/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144625615","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Asrij/OCIAD1 expression delineates functionally distinct hematopoietic stem cells in the bone marrow.","authors":"Aishwarya Prakash, Souvik Halder, Maneesha S Inamdar","doi":"10.1016/j.exphem.2025.105266","DOIUrl":"https://doi.org/10.1016/j.exphem.2025.105266","url":null,"abstract":"<p><p>Hematopoietic stem cells (HSCs) within the bone marrow (BM) display significant molecular and functional heterogeneity. Deciphering intrinsic factors that govern HSC diversity is key to enriching specific HSC subtypes for predictable and clinically relevant differentiation outcomes. Here, we show that the mitochondrial protein Asrij/OCIAD1, a conserved regulator of hematopoietic homeostasis, contributes to HSC heterogeneity. Asrij depletion is known to cause loss of quiescence, myeloid bias and aging-like changes in mouse BM HSCs. Interestingly, Asrij expression is inherently heterogeneous and enriched in only 47% of the HSC population. To investigate whether Asrij expression levels influence HSC fate, we generated a novel Asrij-mNeonGreen knock-in reporter mouse using CRISPR-Cas9 technology. We show that the Asrij reporter faithfully recapitulates its heterogeneous expression in the BM HSCs, allowing isolation of live cells based on Asrij expression levels. Ex-vivo culture of HSCs demonstrated that Asrij^low HSCs exhibit enhanced self-renewal capacity, whereas Asrij^high HSCs are primed for differentiation. Transplantation assays further revealed that Asrij^low HSCs have enhanced reconstitution in the BM hematopoietic stem and progenitor cell (HSPC) and myeloid cell compartments. Transcriptomic analysis uncovered signatures of quiescence in Asrij^low HSCs, while Asrij^high HSCs exhibit hallmarks of HSC activation. In summary, we show that Asrij levels impact the quiescence, self-renewal, and differentiation potential of HSCs, thereby contributing to the functional diversity of the HSC pool. Further, the Asrij-mNeonGreen reporter mouse provides a powerful and versatile model for investigating the molecular underpinnings of functional diversity within the HSC compartment. TEASER ABSTRACT: Our study addresses the complexities of hematopoietic stem cell (HSC) heterogeneity and uncovers novel determinants that govern long-term (LT) reconstituting HSC function. Using a novel Asrij-mNeonGreen fluorescent reporter mouse, we show that the mitochondrial protein Asrij/OCIAD1 regulates HSC heterogeneity. We show that low Asrij expression marks quiescent HSCs with robust self-renewal capacity, whereas high Asrij expression identifies activated, differentiation-primed HSCs. These findings position Asrij as a novel determinant of HSC heterogeneity and introduce the Asrij-mNeonGreen reporter as a versatile tool for dissecting stem cell fate decisions in-vivo.</p>","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":" ","pages":"105266"},"PeriodicalIF":2.1,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145225340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mer receptor expression promotes multiple myeloma disease development via a cell-extrinsic mechanism","authors":"Justine R. Clark ,&nbsp;Vasilios Panagopoulos ,&nbsp;Jacqueline E. Noll ,&nbsp;Krzysztof M. Mrozik ,&nbsp;Alanah L. Bradey ,&nbsp;Peter I. Croucher ,&nbsp;Andrew C.W. Zannettino ,&nbsp;Kate Vandyke ,&nbsp;Duncan R. Hewett","doi":"10.1016/j.exphem.2025.104842","DOIUrl":"10.1016/j.exphem.2025.104842","url":null,"abstract":"<div><div>Multiple myeloma (MM) is an incurable hematologic malignancy characterized by the uncontrolled proliferation of bone marrow resident plasma cells (PCs). Two members of the TAM (TYRO3, AXL, and MER) receptor family have previously been implicated in distinct aspects of neoplastic PC biology. AXL expression in MM PCs has been associated with the induction of a dormant, noncycling state within the bone marrow, whereas expression of MER has been implicated in PC proliferation and survival. Here, the generation of single TAM receptor-expressing 5TGM1 murine MM cell lines enabled the individual functional assessment of the effects of Axl and Mer receptor expression on MM development. Axl expression did not affect proliferation, cell cycling, or stromal cell-induced dormancy in vitro. Development of 5TGM1 tumors in C57BL/KaLwRij mice was also unaltered by Axl expression. By contrast, Mer expression conferred an increase in cell proliferation to 5TGM1 cells in vitro and increased 5TGM1 tumor burden in C57BL/KaLwRij mice. The protumorigenic properties of Mer were only observed following intravenous cell delivery into mice with an intact adaptive immune system. Thus, Axl is neither necessary nor sufficient for the induction of MM cancer cell dormancy, whereas MER remains a promising target for therapeutic intervention in patients with MM.</div></div>","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":"150 ","pages":"Article 104842"},"PeriodicalIF":2.1,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144309787","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}