Experimental hematology最新文献_第4页

Hematopoietic stem cells in human fetal liver selectively express CD49f. 人胎儿肝脏造血干细胞选择性表达CD49f。

IF 2.5 4区医学

Experimental hematology Pub Date : 2025-04-29 DOI: 10.1016/j.exphem.2025.104788

Margarita E MacAldaz, Jeremy Shu, Glenn Edin, Margaret Hale, Connie J Eaves

{"title":"Hematopoietic stem cells in human fetal liver selectively express CD49f.","authors":"Margarita E MacAldaz, Jeremy Shu, Glenn Edin, Margaret Hale, Connie J Eaves","doi":"10.1016/j.exphem.2025.104788","DOIUrl":"10.1016/j.exphem.2025.104788","url":null,"abstract":"<p><p>Identification of phenotypes of human hematopoietic cells that display long-term mature cell outputs in vitro and repopulating capability in immunodeficient mice has been important to anticipating the therapeutic potential of fresh harvests of bone marrow or cord blood before or after their physical or genetic manipulation. However, characterizing their key properties and strategies for their isolation from multiple sources at increasing cell purities and elucidating the mechanisms that regulate their ability to sustain mature blood cell production continues to be of major interest. Previous studies have shown that fetal and adult human cells with long-term blood cell output potential are highly enriched in their respective glycosylphosphatidylinositol (GPI)-anchored surface protein GPI80+ and CD49f+ subsets of a developmentally preserved CD45+CD34+CD38-CD45RA-CD90+ population. The so-called \"GPI80\" hematopoietic cells found in first-trimester human fetal liver are of particular interest because of their very high regenerative capability compared with their adult or even neonatal (cord blood) \"CD49f\" counterparts. Here, it was hypothesized that high regenerative activity of the GPI80+ cells could be further enriched within a CD49f+ subset. We now demonstrated that coexpression of CD49f within the GPI80+ population identifies a subset with reduced short-term myeloid colony-forming activity in semisolid medium and greater progeny outputs in both 12-week growth factor-supplemented stromal cocultures and in transplanted immunodeficient mice. These findings demonstrated that CD49f is a pervasive marker of human hematopoietic stem cells (HSCs) throughout ontogeny and aging.</p>","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":" ","pages":"104788"},"PeriodicalIF":2.5,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143980895","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}

引用次数: 0

Development and aging of resident endothelial stem cells in pre-existing blood vessels. 血管内皮干细胞的发育和衰老。

IF 2.5 4区医学

Experimental hematology Pub Date : 2025-04-29 DOI: 10.1016/j.exphem.2025.104795

Fitriana N Rahmawati, Nobuyuki Takakura

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Engineered cytokine-expressing MSCs support ex vivo culture of human HSPCs and AML cells 表达工程化细胞因子的MSCs支持人造血干细胞和AML细胞的体外培养。

IF 2.5 4区医学

Experimental hematology Pub Date : 2025-04-22 DOI: 10.1016/j.exphem.2025.104790

Johannes Foßelteder , Thomas Brauchart , Angelika Schlacher , Tommaso Sconocchia , Erdem Özkaya , Lisa Auinger , Peter Schlenke , Heinz Sill , Armin Zebisch , Andreas Reinisch

{"title":"Engineered cytokine-expressing MSCs support ex vivo culture of human HSPCs and AML cells","authors":"Johannes Foßelteder , Thomas Brauchart , Angelika Schlacher , Tommaso Sconocchia , Erdem Özkaya , Lisa Auinger , Peter Schlenke , Heinz Sill , Armin Zebisch , Andreas Reinisch","doi":"10.1016/j.exphem.2025.104790","DOIUrl":"10.1016/j.exphem.2025.104790","url":null,"abstract":"<div><div>CD34<sup>+</sup> human hematopoietic stem and progenitor cells and primary patient-derived leukemia cells are important tools for basic and translational research. Their limited availability demands additional expansion ex vivo in many cases. The use of either cytokine cocktails or cocultures with mesenchymal stromal cells (MSCs) has advanced cell expansion but combinations of both have not been addressed extensively so far. Here, we presented a novel approach to generating human cytokine-expressing MSCs (ceMSCs) using genetic engineering. Coculture with ceMSCs and their culture supernatant led to an efficient expansion and maintenance of functional CD34<sup>+</sup>CD45RA<sup>-</sup>CD90<sup>+</sup>CD201<sup>+</sup>CD49c<sup>+</sup> hematopoietic stem cells ex vivo. Similarly, ceMSCs and their culture supernatant support the growth of cytokine-dependent leukemic cell lines in vitro and improve the survival, maintenance, and expansion of patient-derived acute myeloid leukemia cells, a cell population very challenging to be cultured ex vivo<em>.</em> ceMSCs even surpass the support provided by wild-type MSCs or external cytokines alone. Therefore, ceMSCs offer a cost-effective, straightforward alternative to traditional cytokine supplementation, enhancing the feasibility of ex vivo studies on healthy and leukemic stem and progenitor cells, including therapeutic drug testing and mechanistic investigations.</div></div>","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":"147 ","pages":"Article 104790"},"PeriodicalIF":2.5,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144001276","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}

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Unbiased analysis of NUP98-KDM5A-induced murine leukemia reveals phenotypic heterogeneity recapitulating human disease subtypes 对nup98 - kdm5a诱导的小鼠白血病的无偏分析揭示了再现人类疾病亚型的表型异质性。

IF 2.5 4区医学

Experimental hematology Pub Date : 2025-04-20 DOI: 10.1016/j.exphem.2025.104791

Marilaine Fournier , Marion Dubuissez , Mathieu Neault , Jean-Sébastien Delisle , Frédérick A. Mallette , Heather J. Melichar

{"title":"Unbiased analysis of NUP98-KDM5A-induced murine leukemia reveals phenotypic heterogeneity recapitulating human disease subtypes","authors":"Marilaine Fournier , Marion Dubuissez , Mathieu Neault , Jean-Sébastien Delisle , Frédérick A. Mallette , Heather J. Melichar","doi":"10.1016/j.exphem.2025.104791","DOIUrl":"10.1016/j.exphem.2025.104791","url":null,"abstract":"<div><div>NUP98-KDM5A (NK5) is an oncogenic fusion protein implicated in the development of several types of acute myeloid leukemia (AML) in humans, including rare pediatric acute megakaryoblastic leukemia (AMKL). NK5 expression in murine hematopoietic progenitor cells can induce AML in mice. However, the limited number of animals and phenotypic markers used in previous studies preclude the full characterization of the AML subtypes that develop. We used NK5-transduced hematopoietic progenitor cells from murine fetal liver to generate a large cohort of mice. We then assessed the expression of a panel of myeloid markers to characterize the lineage of leukemic blasts using flow cytometry. Finally, we used bioinformatic tools to perform an unbiased analysis of mouse-to-mouse heterogeneity in leukemic cellular phenotypes. We identified phenotypically distinct subgroups among the NK5 leukemias that were predominantly segregated based on the expression of the AMKL-associated marker CD41. Our findings indicate that NK5 expression in fetal liver cells causes different types of leukemia similar in proportion to that observed in pediatric patients. The heterogeneity and mixed phenotypes observed might explain the difficulty in accurately diagnosing leukemia in some patients carrying the NK5 fusion. In addition, this approach may enable the identification of the molecular or cellular basis of the diverse NK5-driven AML types.</div></div>","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":"147 ","pages":"Article 104791"},"PeriodicalIF":2.5,"publicationDate":"2025-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144001277","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}

引用次数: 0

Patterns of hemolysis, erythropoiesis, and iron distribution define unique disease trajectories in three mouse models of genetic anemia 在三种遗传性贫血小鼠模型中，溶血、红细胞生成和铁分布的模式定义了独特的疾病轨迹。

IF 2.5 4区医学

Experimental hematology Pub Date : 2025-04-15 DOI: 10.1016/j.exphem.2025.104787

Irina L. Dubach, Raphael M. Buzzi, Dominik J. Schaer, Florence Vallelian

{"title":"Patterns of hemolysis, erythropoiesis, and iron distribution define unique disease trajectories in three mouse models of genetic anemia","authors":"Irina L. Dubach, Raphael M. Buzzi, Dominik J. Schaer, Florence Vallelian","doi":"10.1016/j.exphem.2025.104787","DOIUrl":"10.1016/j.exphem.2025.104787","url":null,"abstract":"<div><div>Hemolytic anemias involve premature red blood cell (RBC) destruction and present complex phenotypes, including disturbances in iron metabolism, extramedullary erythropoiesis, and systemic organ involvement. To guide the selection of appropriate <em>murine</em> models for studying pathophysiology and pharmacologic treatments of human hemolytic disorders, we systematically characterized three genetic mouse models commonly used to investigate such conditions: sickle cell disease (SCD), β-thalassemia (THAL), and hereditary spherocytosis (SPH). We sought to clarify how these models differ in the severity and nature of hemolysis, the balance between erythropoietic responses and iron regulation, and the long-term patterns of iron distribution. Our findings reveal that SPH mice exhibit severe intravascular hemolysis and suppressed hepcidin levels, leading to unopposed intestinal iron absorption and extensive tissue iron loading, especially in the liver. In contrast, SCD and THAL mice display predominantly extravascular hemolysis, moderate anemia, relatively stable hepcidin levels, and balanced erythropoiesis with partially regulated iron overload. Single-cell ribonucleic acid (RNA) sequencing of spleens highlighted distinct erythropoietic progenitor distributions, whereas iron-isotope tracing experiments confirmed divergent RBC turnover kinetics and tissue distribution. This study defines distinct disease trajectories for common hemolytic disease models by providing a unique comparative framework. Our work will support more informed model selection and refined experimental design to investigate hemolytic anemia pathobiology and therapeutics.</div></div>","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":"147 ","pages":"Article 104787"},"PeriodicalIF":2.5,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143999402","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}

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Corrigendum to A novel lymphoid progenitor cell population (LSKlow) is restricted by p18INK4c Experimental Hematology Volume 44 Issue 9 (2016), 874-844.e5 一种新的淋巴祖细胞群（LSKlow）受到p18INK4c实验血液学卷44第9期（2016），874-844.e5的限制

IF 2.5 4区医学

Experimental hematology Pub Date : 2025-04-05 DOI: 10.1016/j.exphem.2025.104770

Fang Dong , Sha Hao , Shihu Ma , Hui Cheng , Yajie Wang , Wen Zhou , Weiping Yuan , Hideo Ema , Tao Cheng

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Bcl7b and Bcl7c subunits of BAF chromatin remodeling complexes are largely dispensable for hematopoiesis BAF染色质重塑复合物的Bcl7b和Bcl7c亚基在造血中是必不可少的。

IF 2.5 4区医学

Experimental hematology Pub Date : 2025-04-03 DOI: 10.1016/j.exphem.2025.104769

Pierre Priam , Veneta Krasteva , Alexandre Polsinelli , Laurence Côté , Francis Dilauro , Thérèse-Marie Poinsignon , Pierre Thibault , Julie A. Lessard

{"title":"Bcl7b and Bcl7c subunits of BAF chromatin remodeling complexes are largely dispensable for hematopoiesis","authors":"Pierre Priam , Veneta Krasteva , Alexandre Polsinelli , Laurence Côté , Francis Dilauro , Thérèse-Marie Poinsignon , Pierre Thibault , Julie A. Lessard","doi":"10.1016/j.exphem.2025.104769","DOIUrl":"10.1016/j.exphem.2025.104769","url":null,"abstract":"<div><div>Chromatin remodelers have emerged as prominent regulators of hematopoietic cell development and potential drivers of various human hematological malignancies. ATP-dependent BAF chromatin remodeling complexes, related to yeast SWI/SNF, determine gene expression programs and consequently contribute to the self-renewal, commitment, and lineage-specific differentiation of hematopoietic stem cells (HSCs) and progenitors. Here, we investigated the elusive biological function of the core Bcl7b and Bcl7c subunits of BAF complexes in hematopoietic tissue. Our analysis of mouse constitutive knockout alleles revealed that both Bcl7b and Bcl7c are dispensable for animal survival and steady-state adult hematopoiesis. <em>Bcl7b</em> and <em>Bcl7c</em> double knockout (dKO) mice can maintain long-term hematopoiesis with no observable effect on the HSC compartment. Moreover, we show that <em>Bcl7b/Bcl7c</em> dKO HSCs are capable of normal multilineage hematopoietic reconstitution after competitive serial transplantation. Collectively, these studies suggest that the Bcl7b and Bcl7c subunits of BAF complexes are dispensable for normal hematopoiesis.</div></div>","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":"146 ","pages":"Article 104769"},"PeriodicalIF":2.5,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143788239","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}

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IFC Editorial Board IFC编委会

IF 2.5 4区医学

Experimental hematology Pub Date : 2025-04-01 DOI: 10.1016/j.exphem.2025.104754

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Establishing a low-dose x-ray irradiation protocol for experimental acute graft-versus-host disease 建立实验性急性移植物抗宿主病的低剂量x射线照射方案。

IF 2.5 4区医学

Experimental hematology Pub Date : 2025-03-29 DOI: 10.1016/j.exphem.2025.104765

Michelle Klesse , Oliver Schanz , Annkristin Heine

{"title":"Establishing a low-dose x-ray irradiation protocol for experimental acute graft-versus-host disease","authors":"Michelle Klesse , Oliver Schanz , Annkristin Heine","doi":"10.1016/j.exphem.2025.104765","DOIUrl":"10.1016/j.exphem.2025.104765","url":null,"abstract":"<div><div>The investigation of graft-versus-host disease (GvHD) after allogeneic stem cell transplantation heavily relies on the use of experimental animal models and total body irradiation (TBI) as a conditioning regimen. However, <sup>137</sup>Cs is gradually being replaced as the main source of radiation due to safety concerns, and the transfer of established irradiation protocols to x-ray irradiators has proven difficult. Here, we describe the establishment of an x-ray–based irradiation protocol in an experimental mouse model for acute GvHD (C57BL6 → BALB/c). Our data show that commonly reported dosages of 6–9 Gy did not result in a viable model. Instead, irradiation with 5 Gy led to the development of clinical symptoms of GvHD in mice after transplantation with allogeneic bone marrow and T cells. Mice with GvHD displayed altered hemograms and increased serum levels of proinflammatory cytokines compared with mice without GvHD, which was accompanied by sequestration of donor lymphocytes within organs. Donor chimerism and hemogram analyses also indicated sufficient myeloablation and hematopoietic reconstitution. Overall, we show that low-dose x-ray TBI effectively promotes acute GvHD in a mismatched mouse model. We also propose that the transfer of previously established gamma-ray TBI protocols should be carefully evaluated according to individual circumstances.</div></div>","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":"146 ","pages":"Article 104765"},"PeriodicalIF":2.5,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143751820","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}

引用次数: 0

Assessing the impact of cell isolation method on B cell gene expression using next-generation sequencing 利用下一代测序技术评估细胞分离方法对B细胞基因表达的影响。

IF 2.5 4区医学

Experimental hematology Pub Date : 2025-03-29 DOI: 10.1016/j.exphem.2025.104766

Amanda N. Henning, Jordan Pardoe, Darryl Owusu-Ansah, Hong Lei, Kobe Robichaux, Lara Perinet, Samantha Muccilli, Steven L. Highfill, Valeria De Giorgi

{"title":"Assessing the impact of cell isolation method on B cell gene expression using next-generation sequencing","authors":"Amanda N. Henning, Jordan Pardoe, Darryl Owusu-Ansah, Hong Lei, Kobe Robichaux, Lara Perinet, Samantha Muccilli, Steven L. Highfill, Valeria De Giorgi","doi":"10.1016/j.exphem.2025.104766","DOIUrl":"10.1016/j.exphem.2025.104766","url":null,"abstract":"<div><div>Transcriptional profiling of peripheral blood mononuclear cells (PBMCs) is a widely explored research approach across multiple fields. Cell populations of interest are generally isolated before analysis, especially if low-frequency cell populations are desired. B cells, in particular, make up approximately 5%–10% of total PBMCs in healthy individuals, thus, isolation of B cell populations is crucial for researchers investigating B cell malignancies. The most widely used cell isolation methods include negative or positive magnetic cell sorting (MCS) and fluorescence-activated cell sorting (FACS). In contrast to negative MCS, it is widely believed that positive MCS and FACS may affect gene expression due to the direct interaction of cell selection antibodies with surface markers. To the best of our knowledge, no specific studies have examined these effects within CD19<sup>+</sup> B cell populations. To evaluate this, we have performed RNA sequencing (RNA-seq) on B cells isolated from four healthy donors using three distinct methods: positive and negative MCS using the EasySep StemCell Technologies kits and FACS, performed using the MACSQuant Tyto sorter (Miltenyi Biotec). We report significant gene expression changes following CD19-dependent B cell isolation via either positive MCS or FACS relative to negative MCS, including a general upregulation of genes associated with immune activity and receptor signaling and downregulation of RNA processing genes. These results suggest that B cell isolation methods should be taken into consideration when designing experiments or incorporating publicly available sequencing datasets into ongoing research studies, as they may significantly impact the reliability and interpretability of the findings.</div></div>","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":"146 ","pages":"Article 104766"},"PeriodicalIF":2.5,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143751819","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}

引用次数: 0