Experimental hematology最新文献_第3页

Vesicle-mediated information transfer in cardiovascular cell differentiation 心血管细胞分化中囊泡介导的信息传递。

IF 2.5 4区医学

Experimental hematology Pub Date : 2025-05-09 DOI: 10.1016/j.exphem.2025.104800

Jun K. Yamashita

{"title":"Vesicle-mediated information transfer in cardiovascular cell differentiation","authors":"Jun K. Yamashita","doi":"10.1016/j.exphem.2025.104800","DOIUrl":"10.1016/j.exphem.2025.104800","url":null,"abstract":"<div><div>Extracellular vesicles (EVs)—including exosomes, microvesicles, and apoptotic bodies—are membrane-bound carriers of diverse molecular cargo such as nucleic acids, proteins, and lipids. They are increasingly recognized as critical mediators of information transfer during cardiovascular cell differentiation, development, diseases, and regeneration. Emerging evidence highlights the capacity of EV-encapsulated microRNAs (miRNAs) to drive cardiomyocyte differentiation and support angiogenesis. We recently discovered a novel EV-mediated mechanism termed “phenotypic synchronization of cells” (PSyC). When protein kinase A (PKA) is activated in pluripotent stem cells, the speed of mesodermal differentiation increases, partly through elevated EV-encapsulated miR-132. miR-132, transferred to neighboring cells with EVs, reactivates PKA signaling in recipient cells, synchronizing differentiation stages. Additionally, ex vivo assays reveal that EVs derived from PKA-activated cells can induce cardiomyocyte differentiation in early-stage embryos, underscoring the potency of EV-based signaling in shaping cardiovascular phenotypes. We recently uncovered a novel modality of vesicle-mediated intercellular communication, named direct intercellular vesicle exchange (DIVE), a distinct pathway enabling rapid and direct vesicle transfer between adjacent cells. By facilitating the direct traverse of nucleic acid-laden vesicles across the plasma membrane, DIVE may reinforce conventional EV-based signaling in cardiovascular differentiation. Together, these findings underscore the fundamental role of vesicle-mediated information exchange in orchestrating cardiac and vascular cell fates. Exploiting vesicle-mediated communication may open new avenues in regenerative medicine, disease modeling, and therapeutic interventions aimed at modulating cardiovascular cell function.</div></div>","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":"148 ","pages":"Article 104800"},"PeriodicalIF":2.5,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143976599","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

Ontogeny, dynamics, and characteristics of neutrophils during the perinatal period 围产期中性粒细胞的个体发生、动态和特征。

IF 2.5 4区医学

Experimental hematology Pub Date : 2025-05-09 DOI: 10.1016/j.exphem.2025.104798

Ryo Ishiwata

{"title":"Ontogeny, dynamics, and characteristics of neutrophils during the perinatal period","authors":"Ryo Ishiwata","doi":"10.1016/j.exphem.2025.104798","DOIUrl":"10.1016/j.exphem.2025.104798","url":null,"abstract":"<div><div>This review examined the dynamic development and unique characteristics of neutrophils during the perinatal period, a critical window when the immune system undergoes rapid reprogramming, based on the mouse studies. In the mouse fetal liver—the primary hematopoietic niche before birth—hematopoietic stem cells and progenitor cells expand in parallel, with granulocyte–monocyte progenitors preferentially differentiating into neutrophils during late gestation. This process, partly driven by granulocyte colony-stimulating factor (G-CSF), substantially increases the number of neutrophils, preparing the neonates for microbial challenges after birth. After birth, there is a surge in circulating neutrophils, likely due to the mobilization of neutrophils from the liver, followed by a microbiota-dependent activation of granulopoiesis in the bone marrow. In addition to their antimicrobial functions, neonatal neutrophils exhibit immunomodulatory characteristics, such as reduced proinflammatory signaling and diminished neutrophil extracellular trap formation. These traits may contribute to tolerance to the microbes and help mitigate excessive inflammation. Finally, unresolved issues related to the phenotypic diversity and precise physiological roles of neutrophils during the perinatal period are addressed, highlighting the need for further research.</div></div>","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":"148 ","pages":"Article 104798"},"PeriodicalIF":2.5,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143965069","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

Notch1 activation and inhibition in T-cell acute lymphoblastic leukemia subtypes Notch1在T细胞急性淋巴细胞白血病亚型中的激活和抑制作用。

IF 2.5 4区医学

Experimental hematology Pub Date : 2025-05-08 DOI: 10.1016/j.exphem.2025.104771

Jiawen Lu , Xiuhua Xue , Haitao Wang , Ying Hao , Qiong Yang

引用次数: 0

A distinct alternative mRNA splicing profile identifies the oncogenic CD44 transcript variant 3 in KMT2A-rearranged pediatric T-cell acute lymphoblastic leukemia cells 在kmt2a重排的儿童t细胞急性淋巴细胞白血病细胞中，一种独特的替代mRNA剪接谱鉴定了致癌CD44转录物变体3

IF 2.5 4区医学

Experimental hematology Pub Date : 2025-05-01 DOI: 10.1016/j.exphem.2025.104712

Amanda Ramilo Amor , Sabina Enlund , Indranil Sinha , Qingfei Jiang , Ola Hermanson , Anna Nilsson , Shahrzad Shirazi Fard , Frida Holm

{"title":"A distinct alternative mRNA splicing profile identifies the oncogenic CD44 transcript variant 3 in KMT2A-rearranged pediatric T-cell acute lymphoblastic leukemia cells","authors":"Amanda Ramilo Amor , Sabina Enlund , Indranil Sinha , Qingfei Jiang , Ola Hermanson , Anna Nilsson , Shahrzad Shirazi Fard , Frida Holm","doi":"10.1016/j.exphem.2025.104712","DOIUrl":"10.1016/j.exphem.2025.104712","url":null,"abstract":"<div><div>T-cell acute lymphoblastic leukemia (T-ALL), which constitutes of 10–15% of all pediatric acute lymphoblastic leukemia (ALL) cases, is known for its complex pathology due to pervasive genetic and chromosomal abnormalities. Although most children are successfully cured, chromosomal rearrangements involving the KMT2A gene is considered a poor prognostic factor. In a cohort of 171 pediatric T-ALL samples, we have studied differences in gene and splice variant patterns in KMT2A-rearranged (KMT2A-r) T-ALL compared with KMT2A-negative (KMT2A-wt) T-ALL samples. Our results have identified a distinct gene expression and splice variant expression pattern in pediatric KMT2A-r patient samples including significant expression of splicing regulatory markers ESRP1 and MBNL3. Additionally, the prosurvival long transcript variant of BCL2 were upregulated in KMT2A-r compared with KMT2A-wt T-ALL samples. Lastly, increased levels of activating methylation in the promoter region of CD44 were identified followed by an upregulation of the oncogenic transcript variant CD44v3 in KMT2A-r T-ALL. Together, this suggests that CD44v3 could play a potential role as gene expression–based risk stratification of KMT2A-r T-ALL and could possibly serve as a therapeutic target using splicing modulators.</div></div>","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":"145 ","pages":"Article 104712"},"PeriodicalIF":2.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142964310","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

Advantages and challenges of ex vivo generation and expansion of human hematopoietic stem cells from pluripotent stem cells 多能干细胞体外生成和扩增人造血干细胞的优势和挑战。

IF 2.5 4区医学

Experimental hematology Pub Date : 2025-05-01 DOI: 10.1016/j.exphem.2025.104752

Min Ding , Yu Lu , Quan-Kai Lei , Yun-Wen Zheng

{"title":"Advantages and challenges of ex vivo generation and expansion of human hematopoietic stem cells from pluripotent stem cells","authors":"Min Ding , Yu Lu , Quan-Kai Lei , Yun-Wen Zheng","doi":"10.1016/j.exphem.2025.104752","DOIUrl":"10.1016/j.exphem.2025.104752","url":null,"abstract":"<div><div>Hematopoietic stem cell transplantation (HSCT) is an essential and increasing therapeutic approach for treating conditions such as leukemia, lymphoma, and other blood cancers. However, its widespread use faces significant challenges, including limited donor availability, pathogens, and the risk of immune rejection. The emergence of pluripotent stem cells (PSCs) offers a potential solution to these challenges. By enabling the generation of hematopoietic stem cells (HSCs) and blood cells in vitro, PSCs open pathways to address the limitations of traditional HSC sources. Self-induced or gene-edited PSCs from patients may provide an accessible and personalized option for clinical applications. In this review, we examine the current protocols for differentiating PSCs into HSCs and blood cells, highlighting their benefits and shortcomings. Despite advancements in this field, two primary challenges persist: low differentiation efficiency and difficulties in isolating and enriching functional HSCs. These problems make it difficult to obtain HSCs for long-term survival. Thus, we propose innovative strategies and potential improvements including induction scheme optimization, reprogramming, and cell fate tracking. Future research should prioritize the development of efficient and reliable differentiation protocols for PSCs to obtain more functional HSCs. Additionally, establishing effective methods for enriching functional HSCs and blood cells will be critical for optimizing their use in clinical applications. These efforts hold the promise of overcoming current limitations and advancing the therapeutic potential of PSC-derived blood cells.</div></div>","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":"145 ","pages":"Article 104752"},"PeriodicalIF":2.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143630286","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

Sex differences alter primitive progenitors in the C57BL/6 Tet2 knockout mouse model 性别差异改变C57BL/6 Tet2敲除小鼠模型中的原始祖细胞。

IF 2.5 4区医学

Experimental hematology Pub Date : 2025-05-01 DOI: 10.1016/j.exphem.2025.104747

Samantha M. Holmes , Christopher J. Wells , Christine Hall , Amy J.M. McNaughton , Michael J. Rauh , Sheela A. Abraham

{"title":"Sex differences alter primitive progenitors in the C57BL/6 Tet2 knockout mouse model","authors":"Samantha M. Holmes , Christopher J. Wells , Christine Hall , Amy J.M. McNaughton , Michael J. Rauh , Sheela A. Abraham","doi":"10.1016/j.exphem.2025.104747","DOIUrl":"10.1016/j.exphem.2025.104747","url":null,"abstract":"<div><div>The precancerous expansion of hematopoietic cells, termed clonal hematopoiesis (CH), has been correlated to disease development and all-cause mortality. Despite multiple observations that hematopoietic stem cell and progenitors (HSPCs) are significantly affected by both sex and age, there remain few studies quantifying male and female HSPC populations in wild-type and transgenic <em>Tet2</em> models over time. Here, we determine that male mice (with a hematopoietic deficiency of <em>Tet2</em> and control) have more Lin<sup>−</sup>Sca-1<sup>+</sup>c-kit<sup>+</sup> (LSK) cells, that include multipotent progenitor cells (MPPs; LSK CD48<sup>−</sup>CD150<sup>−</sup>) and long-term hematopoietic stem cells (LT-HSC; LSK CD48<sup>−</sup>CD150<sup>+</sup>) compared with females. LT-HSC, MPP, and progenitor populations were observed to possess equal male/female ratios in mice at 6 weeks of age; however, the LSK compartment was found most susceptible to sex-based effects in transgenic mice between 6 weeks and 4 months. In contrast, all differentiated progenitor populations analyzed in mice were observed to be unaffected by sex between 6 weeks to 4 months. This study provides a comprehensive analysis of bone-sourced HSPCs in <em>Tet2</em>-deficient mouse models and reveals important sex and age considerations that must be taken into account when using C57BL/6 mice for transgenic studies.</div></div>","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":"145 ","pages":"Article 104747"},"PeriodicalIF":2.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143523041","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

IFC Editorial Board IFC编委会

IF 2.5 4区医学

Experimental hematology Pub Date : 2025-05-01 DOI: 10.1016/S0301-472X(25)00064-5

引用次数: 0

Large-scale mediator Mendelian randomization analysis identifies multiple immune cells mediating the causal link between gut microbes and chronic graft-versus-host disease risk 大规模中介孟德尔随机化分析确定了多种免疫细胞介导肠道微生物和慢性移植物抗宿主病风险之间的因果关系。

IF 2.5 4区医学

Experimental hematology Pub Date : 2025-04-30 DOI: 10.1016/j.exphem.2025.104794

Yiyin Chen , Xinghao Yu , Yiming Cai , Zhou Jin , Yang Xu

{"title":"Large-scale mediator Mendelian randomization analysis identifies multiple immune cells mediating the causal link between gut microbes and chronic graft-versus-host disease risk","authors":"Yiyin Chen , Xinghao Yu , Yiming Cai , Zhou Jin , Yang Xu","doi":"10.1016/j.exphem.2025.104794","DOIUrl":"10.1016/j.exphem.2025.104794","url":null,"abstract":"<div><div>Disorders of gut microbiota and immune cells have been observed to be involved in the occurrence of chronic graft-versus-host disease (cGVHD), but their causal connections have yet to be fully understood. This study utilized Mendelian randomization (MR), integrating genome-wide association study (GWAS) meta-analyses from the MiBioGen consortium (microbial taxa), the SardiNIA project (immune traits), and disease data from the Fred Hutchinson Cancer Research Center (FHCRC) cohort to investigate their relationships. The aim was to explore the causal effects of microbiota and immune traits on the incidence of cGVHD, using mediation analysis to identify which immune traits might mediate the effects of microbiota on this condition. The main analysis observed significant causal associations of 3 specific microbial taxa with cGVHD: <em>Lactococcus.id.1851</em> (odds ratio [OR] = 1.989, 95% confidence interval [CI] = 1.311–3.019, <em>p =</em> 0.001), <em>Ruminiclostridium9.id.11357</em> (OR = 3.273, 95% CI = 1.604–6.679, <em>p =</em> 0.001), and <em>Intestinimonas.id.2062</em> (OR = 0.400, 95% CI = 0.230–0.697, <em>p =</em> 0.001). Sensitivity analysis and multivariable MR analysis ruled out possible horizontal pleiotropy and bias. Additionally, 10 immune traits, predominantly covering regulatory T cells (Tregs) and B cells, were identified as influencing cGVHD risk. The two-step mediation MR analysis presented the effect of identified microbial taxa on Tregs and B cells and detailed the pathways through which <em>Intestinimonas</em> impacts cGVHD via CD27 on memory B cells (proportion mediated = 4.2%). Similarly, the role of interactions between <em>Ruminiclostridium9</em> and effector memory double-negative T cells in mediating cGVHD was quantified, accounting for 9.5% of the total effect.</div></div>","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":"147 ","pages":"Article 104794"},"PeriodicalIF":2.5,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143980232","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

Mtg16 NHR1 mutations cause defects in lymphopoiesis and the response to anemia Mtg16 NHR1突变导致淋巴系统缺陷和对贫血的反应。

IF 2.5 4区医学

Experimental hematology Pub Date : 2025-04-30 DOI: 10.1016/j.exphem.2025.104793

Monica Bomber , Pankaj Acharya , Anna E. Johnson , Shilpa Sampathi , David K. Flaherty , Brittany K. Matlock , Jacob D. Ellis , Luke N. Bartlett , Christopher S. Williams , Scott W. Hiebert , Kristy R. Stengel

{"title":"Mtg16 NHR1 mutations cause defects in lymphopoiesis and the response to anemia","authors":"Monica Bomber , Pankaj Acharya , Anna E. Johnson , Shilpa Sampathi , David K. Flaherty , Brittany K. Matlock , Jacob D. Ellis , Luke N. Bartlett , Christopher S. Williams , Scott W. Hiebert , Kristy R. Stengel","doi":"10.1016/j.exphem.2025.104793","DOIUrl":"10.1016/j.exphem.2025.104793","url":null,"abstract":"<div><div>The Eight-Twenty-One (ETO)/Myeloid Translocation Gene (MTG) family of transcriptional corepressors play a key role in adult stem cell function across multiple tissues and may be affected by mutation, deletion, or translocation in solid tumors and leukemia. Structural studies of the first conserved domain identified residues that make specific contacts with E proteins, such as HEB and E2A. We generated mice with a mutation in a critical phenylalanine (F210A) in Mtg16 to test the physiological significance of Mtg16 association with E proteins and compared these mice to mice containing a nearby cancer-associated mutation (P209T). We found that <em>Mtg16<sup>−/−</sup></em> and <em>Mtg16<sup>F210A/F210A</sup></em> mice showed impaired lymphopoiesis following competitive bone marrow transplant, suggesting that the repression of E protein-dependent transcription is critical for B- and T-cell development. Although <em>Mtg16<sup>−/−</sup>, Mtg16<sup>P209T/P209T</sup></em>, and <em>Mtg16<sup>F210A/F210A</sup></em> animals showed significant defects in burst forming potential (BFU-E) after phenylhydrazine treatment, only <em>Mtg16<sup>−/−</sup></em> mice showed overt signs of anemia. Thus, we propose that, although Mtg16 is a critical regulator of hematopoietic stem and progenitor cell (HSPC) function, response to hemolytic anemia, and lymphoid development, the interaction between Mtg16 and E proteins is particularly important for lymphopoiesis.</div></div>","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":"147 ","pages":"Article 104793"},"PeriodicalIF":2.5,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144005446","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

Distinct transcriptional changes in hematopoietic progenitor subsets on LPS-induced emergency granulopoiesis lps诱导的紧急粒细胞生成中造血祖细胞亚群的明显转录变化。

IF 2.5 4区医学

Experimental hematology Pub Date : 2025-04-30 DOI: 10.1016/j.exphem.2025.104792

Sladjana Kosanovic , Karolina Vanickova , Mirko Milosevic , Irina Ribeiro Bas , Mateusz Chilinski , Dariusz Plewczynski , Petr Danek , Jakub Rohlena , Katerina Rohlenova , Meritxell Alberich-Jorda

{"title":"Distinct transcriptional changes in hematopoietic progenitor subsets on LPS-induced emergency granulopoiesis","authors":"Sladjana Kosanovic , Karolina Vanickova , Mirko Milosevic , Irina Ribeiro Bas , Mateusz Chilinski , Dariusz Plewczynski , Petr Danek , Jakub Rohlena , Katerina Rohlenova , Meritxell Alberich-Jorda","doi":"10.1016/j.exphem.2025.104792","DOIUrl":"10.1016/j.exphem.2025.104792","url":null,"abstract":"<div><div>Emergency granulopoiesis is a critical process by which hematopoietic progenitors and stem cells facilitate enhanced granulocytic production during severe infections. However, the role of distinct multipotent progenitors (MPPs) at early stages of this process remains underexplored. Here, we investigated the contribution of MPPs to granulocytic production following lipopolysaccharide (LPS) administration in wild-type mice, simulating a bacterial infection. Transplantation assays demonstrated that LPS exposure reduces the engraftment capacity of lymphoid-biased MPP4 and enhances lymphoid production, rather than supporting myeloid lineage output. Further, single-cell RNA sequencing (scRNA-seq) of MPPs isolated from control and LPS-challenged mice revealed transcriptional reprogramming of nonlineage committed MPPs toward myeloid- and erythroid-biased progenitors. Notably, inflammatory progenitor populations emerged on activation of LPS-induced emergency granulopoiesis, displaying chromatin accessibility changes that align with a commitment to myeloid and erythroid fates. Pseudotime analysis elucidated cellular trajectories that suggest a developmental pathway where unbiased progenitors, present under nonstress conditions, transition toward myeloid and erythroid lineage outputs on LPS administration. In line with our functional MPP4 assessment, scRNA-seq suggested that lymphoid-biased progenitors do not transcriptionally rewire during early stages of emergency granulopoiesis. Collectively, our data highlight the critical role of specific MPP subsets in responding to LPS-induced inflammatory signals and underscore the dynamic adaptations that occur during granulocyte production in response to infection.</div></div>","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":"147 ","pages":"Article 104792"},"PeriodicalIF":2.5,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143963814","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