搜索结果：Stem cell reports

Studying neural-related questions is inherently challenging due to the limited number of suitable cell models. Here, we characterize a previously reported immortalized human neural stem cell line, HNSC.100, serving as a robust model for a wide range of neurobiological research questions. The cell line expresses key neural stem cell markers, including SOX2, vimentin, nestin, and allows for efficient genetic manipulation. Furthermore, HNSC.100 cells can be differentiated into neurons, astrocytes, and oligodendrocytes, thereby covering a wide spectrum of major neural cell types. We adapted corresponding differentiation protocols and established a comprehensive panel of molecular markers to validate successful differentiation, enabling precise characterization of the resulting cell population. In addition, we provide a complete dataset of RNA expression levels for all detectable genes in HNSC.100 cells. Based on this dataset, we assembled a list of expressed genes implicated in neural disorders that can be studied with this cell line. Together, we present a detailed characterization of the HNSC.100 cell line and provide new tools and reference data to facilitate its use. This resource enables researchers to evaluate the line's suitability for specific applications and to rapidly integrate HNSC.100 cells into their experimental workflows.

Neurogenesis in adult mammalian brain persists in restricted areas, especially the subgranular zone (SGZ) of the hippocampus and the ventricular-subventricular zone (V-SVz), where neural stem cells (NSCs) occupy neurogenic niches. These NSC niches provide signals that regulate stem cell behavior. Among extrinsic modulators, Growth Differentiation Factor 11 (GDF11 or BMP11) which is a transforming growth factor-β (TGF-β) superfamily member, was shown to play key role in the NSC biology and brain aging. In this review, the most recent molecular mechanisms of GDF11 signaling in the regulation of NSC will be addressed. GDF11 plays mainly through activin type II receptors (ActRIIA/B) and ALK4/ALK5, activating classical Smad2/3 pathways that impact transcriptional networks controlling neural cell behavior. Moreover, GDF11 stimulates non-Smad signaling pathways - including ERK, p38, JNK, and PI3K/AKT - providing context-dependent integration of proliferative and anti-proliferative signals. Furthermore, GDF11 functions as a feedback regulator limiting the number of progenitor cells and organizing neurogenic timing. In the adult brain, GDF11 plays important role in neurovascular remodeling, glial inflammatory states, and extracellular matrix interactions. Despite its recognized roles, the effect of GDF11 on aging remains a subject of intense debate, characterized by conflicting reports regarding its circulating levels, tissue-specific dynamics, and dose-dependent effects. Recent evidence suggests that GDF11 acts as a context-dependent modulator, integrating systemic, vascular, and cellular cues to maintain NSC homeostasis and neurogenic potential. Therefore, elucidating the exact cellular and molecular mechanisms by which GDF11 controls NSC behavior is vital to advancing novel therapeutic strategies for neurodegenerative disorders and age-related cognitive decline.

Stem cell research offers unique opportunities for authentic scientific engagement, yet infrastructure requirements have confined participation to elite institutions, perpetuating workforce disparities. We developed an integrated framework combining stem cell engineering, cloud-connected microscopy, and psychometric assessment. The framework integrates a doxycycline-inducible NGN2 mouse embryonic stem cell (mESC) system, low-cost cloud microscopy, and the Stem Cell Research Identity Scale (SCRIS). Implementation across a high school and a community college demonstrated significant increases in scientific identity. Students using differentiating PSCs showed broader science identity gains than those using neuroblastoma cells, particularly in competence, research readiness, and recognition. High school students showed enhanced research competence gains compared to community college students despite equivalent intervention duration. Demographic analyses revealed enhanced effectiveness for Hispanic and first-generation college students. This framework provides a scalable model for broadening participation in biomedical research.

Human endometrium sheds and regenerates each month during the menstrual cycle. N-cadherin+ (CDH2) glandular epithelial progenitors and SUSD2+ mesenchymal stem cells (MSCs) and their niches have been identified, but their signaling interactions remain unknown. SSEA1+ epithelial cells resurface the endometrium, generating a new luminal epithelium each cycle. Using these markers, we characterized the gene expression of human endometrial stem/progenitor cell-enriched populations derived from fluorescence-activated cell sorting (FACS)-sorted hysterectomy endometrium by single-cell RNA sequencing (scRNA-seq). Two of 10 epithelial clusters contained CDH2+SOX9+ cells with high TRH and IHH expressions. N-cadherin and IHH, and SSEA1 and Hedgehog co-receptor BOC immunoco-localized in the basal layer of endometrial glands, from which the new functional layer glands regenerate each menstrual cycle. Two of six mesenchymal clusters contained SUSD2+ MSCs, one with high MUSTN1 expression. Epithelial progenitors and endometrial MSCs transitioned to their respective progeny. We provide new insights into the human endometrial stem/progenitor cell signaling pathways and niche interactions regulating their function.

Brainstem metastasis from small-cell lung cancer (SCLC) is exceedingly rare and is associated with a dismal prognosis. This study presents a case of brainstem metastasis from SCLC treated with the TMEp-CI-M platform, achieving no evidence of disease (NED) for more than 20 months. The TMEp-CI-M platform is designed to overcome resistance in immunologically "cold" tumors through sequential tumor microenvironment priming (TMEp), checkpoint inhibition (CI), and microbiome modulation. We have previously reported its efficacy in pancreatic neuroendocrine carcinoma, hepatocellular carcinoma, pancreatic ductal adenocarcinoma, non-small cell lung cancer (NSCLC), and colorectal cancer. A 60-year-old male with programmed death ligand 1 (PD-L1)-negative extensive-stage small-cell lung cancer (ES-SCLC) and brainstem metastasis received the TMEp-CI-M regimen. The TMEp phase integrated stereotactic body radiotherapy (SBRT), low-dose etoposide, and anlotinib, followed by CI with the programmed death 1 (PD-1)/cytotoxic T lymphocyte antigen 4 (CTLA-4) bispecific antibody cadonilimab and concurrent probiotic supplementation. The patient's pro-gastrin-releasing peptide (ProGRP) level normalized after the first cycle (from 1803 pg/mL to 23.71 pg/mL) during a total of 6 treatment cycles. At the time of this report (20 months after treatment initiation), the patient remains NED, with only Grade 1 hypothyroidism as an adverse event. The TMEp-CI-M platform may enhance the efficacy of immunotherapy in ES-SCLC, enabling durable responses even in patients with brainstem metastases. Although this platform has demonstrated promise across multiple tumor types, further prospective and mechanistic studies are warranted to confirm its clinical utility.

Here, we ask how adult neural stem cells (NSCs) arise developmentally, focusing on murine cortical precursors that generate excitatory neurons embryonically and interneurons and glial cells postnatally. Using complementary single-cell spatial, transcriptomic, and epigenomic approaches, we show that postnatal NSC state acquisition involves a gradual transcriptional and epigenetic shift in the entire embryonic cortical precursor cell population and identify a distinct transition precursor state at E17/18 when both embryonic and the first postnatal progeny are being generated. Non-proliferative adult NSCs are also first seen at this transition timepoint, but they arise in a spatial domain distinct from that of the first postnatal progeny, indicating that NSC state acquisition is not a necessary prelude to the switch in cell genesis. These findings support a gradual epigenetically continuous model for the transition from developing cortical precursors to NSCs and show that this is spatially separable from the transition to generating postnatal cell types.

Brexucabtagene autoleucel (brexu-cel) is an autologous CD19-directed CAR T-cell therapy approved for relapsed/refractory (R/R) mantle cell lymphoma (MCL) based on the pilot study ZUMA-2. Since then, several US and European real-world studies have demonstrated comparable efficacy outcomes. However, these reports have also suggested potentially higher rates of acute toxicities, particularly immune effector cell-associated neurotoxicity syndrome (ICANS), raising concerns regarding its use, especially in vulnerable populations. At Singapore General Hospital, five patients (median age 75 years) received brexu-cel from April 2025 to Dec 2025 for R/R MCL. Historical cohort MCL patients received allogeneic haematopoietic stem cell transplantation (allo-HSCT) were extracted and compared. For brexu-cel cohort, the overall response rate (ORR) was 100%, with a complete response rate (CRR) of 80%. Cytokine release syndrome (CRS) occurred in 80% of patients, with no grade 3 events, and only one patient developed grade 1 ICANS (20%). These efficacy and safety outcomes compare favourably with historical cohorts of patients who underwent allo-HSCT locally (total 6 patients, 2 relapsed, 2 NRM), despite potentially higher-risk features and less controlled disease at baseline. Efficacy and toxicity of both clinical trial and real-world CAR-T studies for R/R MCL were summarized. To our knowledge, this represents the first real-world report from Asia on brexu-cel in R/R MCL, supporting its use in this region, where published data have thus far predominantly originated from the United States and Europe.

CAR T-cell therapy has become a highly effective treatment for hematological malignancies, and emerging evidence indicates promising benefits for non-oncohematological conditions. As its clinical use broadens, understanding long-term outcomes and late complications is crucial. One critical yet understudied area is fertility, for which current evidence remains limited and no formal guidelines provide direction for patients undergoing CAR T-cell therapy. To address this gap, we conducted a cross-sectional survey on behalf of the Cellular Therapy and Immunobiology Working Party (CTIWP) of the European Society for Blood and Marrow Transplantation (EBMT) focusing on current practices, existing challenges, and reported reproductive outcomes. Questionnaires were distributed electronically (via SurveyMonkey) between Jan 8, 2025 and April 18, 2025 to 247 EBMT-affiliated centers assessing current fertility-related practices and procedures around CAR T-cell therapy. A second, complementary questionnaire was circulated between Dec 23, 2025 and April 9, 2026 to gather detailed information on reported pregnancies following CAR T treatment. 99 of 247 (40%) centers answered and were included in the analysis. At data censoring, 24 pregnancies were reported in 19 patients, resulting in 18 live births, 2 ongoing pregnancy (one with twins), and 4 miscarriages. Eighteen pregnancies occurred in female CAR T-cell recipients, and six were reported by male recipients through their partners. In patients achieving pregnancy, B cell lymphoma was the most common indication for treatment. Pregnancies in the female cohort occurred naturally in 83% of cases (15/18). Among patients with data, the median time between CAR T-cell infusion and delivery or miscarriage was 3 years (range 4 months-6 years). Although both low- and high-grade Cytokine Release Syndrome (CRS) and Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) were reported among these patients, these events did not appear to influence pregnancy outcomes, acknowledging the small sample size. While most centers (52/63, 83%) reported offering fertility counselling before CAR T-cell infusion, 11 centers (17%) indicated that they do not routinely inform patients of the potential reproductive risks. Most centers (79%) offered fertility preservation procedures to male and female patients. The most common barriers to fertility preservation referral were the urgency of initiating bridging therapy to CAR T-cell infusions due to active or rapidly progressive disease in aggressive disease and extensive prior chemotherapy exposure, defined as more than three previous treatment lines. For female patients, the predominant approaches were oocyte cryopreservation (63%) and ovarian tissue cryopreservation (59%). Among male patients, semen collection and cryopreservation was the most frequently used method (93%). Endocrinologic follow-up practices after CAR T-cell therapy varied substantially across centers. We report the largest series of pregnancies and live births after CAR T in patients with hematological malignancies and autoimmune diseases, and the first within Europe. As CAR T-cell therapy is increasingly administered earlier in the treatment algorithms and to younger populations, integrating standardized fertility counselling and preservation strategies into routine care will be essential. The reproductive success highlights the urgent need for robust research and formalized guidelines in this evolving field. None.

Collagen XVIIα1, encoded by COL17A1 and historically known as BP180/BPAG2, is a type II transmembrane collagen enriched in hemidesmosomes of basal keratinocytes. Through interactions with integrin α6β4, laminin-332 and other dermal-epidermal junction (DEJ) components, collagen XVIIα1 links the keratin cytoskeleton to the basement membrane. Recent studies indicate that this junctional anchorage supports epidermal homeostasis by preserving stem cell adhesion, polarity and regenerative capacity. During aging, collagen XVIIα1 levels decline and proteolytic processing increases, including ADAM9/ADAM10-dependent ectodomain shedding and cleavage by inflammatory proteases. These changes weaken DEJ integrity and are associated with photoaging and impaired repair. In hair follicles, collagen XVIIα1 is also required for hair follicle stem cell (HFSC) maintenance, and its reduction is linked to HFSC exhaustion, hair aging phenotypes and altered niche signals that may influence melanocyte stem cell-dependent pigmentation. This review summarizes translational approaches targeting collagen XVIIα1 and proposes practical in vivo readouts for target engagement. Key gaps include mechanism attribution, durable functional restoration at the DEJ, persistence within the epidermal-follicular niche and a shortage of rigorous human studies.

Chronic systemic inflammation is a key driver of disease progression in rheumatoid arthritis and chronic kidney disease (CKD), particularly in patients undergoing long-term hemodialysis. Persistent elevation of proinflammatory cytokines contributes to pain, anemia, endothelial dysfunction, and increased cardiovascular risk, while therapeutic options are often limited by comorbidities and drug intolerance. Mesenchymal stem cells (MSCs) possess immunomodulatory properties that may offer an alternative strategy for systemic inflammatory control. We report on the case of a 56-year-old woman with juvenile-onset rheumatoid arthritis and dialysis-dependent CKD who received three consecutive systemic administrations of MSCs. Baseline evaluation demonstrated elevated inflammatory markers, including C-reactive protein, interleukin-6, and tumor necrosis factor-α. Following treatment, inflammatory parameters were consistently reduced, which was accompanied by improvement in hemoglobin levels and favorable trends in renal function markers. Additionally, pain assessment scores (Western Ontario and McMaster Universities Arthritis Index, Knee Injury and Osteoarthritis Outcome Score, Visual Analogue Scale) showed clinically significant improvement. The patient also reported significant subjective pain relief and improved overall well-being. Although limited by its single-case design, this report supports the biological plausibility of systemic MSC therapy as a potential immunomodulatory approach in patients with overlapping autoimmune and uremia-associated chronic inflammation. Further controlled studies are warranted.

Hyperuricemia (HUA) affects diverse biological processes and signaling pathways across multiple organ systems; however, its impact on the intestine remains poorly understood. Here, we show that HUA disrupts intestinal barrier function primarily by impairing intestinal stem cell (ISC) function, which is essential for epithelial renewal. Mechanistically, elevated uric acid (UA) directly binds to the mitochondrial protein CCDC90B, leading to excessive mitochondrial ROS accumulation, activation of the NLRP3 inflammasome, and subsequent initiation of downstream pyroptotic signaling. The resulting exhaustion of the intestinal stem cell pool impairs epithelial regeneration and further weakens intestinal barrier integrity. Collectively, these findings reveal a previously unrecognized mechanism linking UA to ISC dysfunction and highlight CCDC90B as a potential therapeutic target for HUA-associated intestinal dysfunction.

Chimeric antigen receptor (CAR) T cells have shown considerable promise in treating patients with haematological malignancies. We aimed to investigate short-term patient-reported symptomatic adverse events in patients with aggressive B-cell lymphomas treated with CAR T-cell therapy and compare them with those reported by their treating physicians. We also examined factors predicting overall short-term burden of therapy. This was a prospective, observational, multicentre study enrolling patients across 13 centres in Italy. Eligible patients were aged 18 years and older with a confirmed diagnosis of aggressive B-cell lymphoma. All patients were scheduled to undergo CAR T-cell therapy with one of the following products: axicabtagene ciloleucel (axi-cel), tisagenlecleucel (tisa-cel), or brexucabtagene autoleucel (brexu-cel). The primary objective of this analysis was to assess the prevalence of short-term patient-reported symptomatic adverse events overall and by sex and age categories. The primary objective was evaluated on day 10 after infusion via the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE), which includes 19 items selected based on their clinical relevance, including: difficulty swallowing, decreased appetite, nausea, diarrhoea, swelling, hair loss, dizziness, concentration difficulty, memory difficulty, general pain, headache, muscle pain, joint pain, insomnia, fatigue, anxiety, discouragement, sadness, and chills. Prevalence of symptomatic adverse events was also assessed by type of CAR T-cell product. Additionally, the study was designed to allow a corresponding adverse event assessment via the CTCAE by treating haematologists for comparative analysis. Adverse events reported by physicians were matched with corresponding adverse events reported by patients. Furthermore, an overall symptom burden score was computed and used as outcome variable in multivariable analysis to examine factors predicting short-term burden of therapy, including sociodemographic and clinical data and pre-infusion patient-reported physical functioning by the EORTC QLQ-C30. The study is registered with ClinicalTrials.gov, NCT06026644, and is closed to accrual and follow-up is complete. Between June 29, 2022, and Feb 26, 2024, 170 patients were included in the study. The median age of patients was 61·1 years (IQR 51·1-68·5) and the median follow-up was 23·7 months (17·7-24·6). 53 (31%) of 170 enrolled patients were female and 117 (69%) were male. Most patients were diagnosed with diffuse large B-cell lymphoma (118 [69%] patients), followed by mantle cell lymphoma (32 [19%] patients) and primary mediastinal large B-cell lymphoma (20 [12%] patients). 98 (58%) patients were infused with axi-cel, 39 (23%) with tisa-cel, and 32 (19%) with brexu-cel. 165 patients reached the day 10 timepoint, of whom 143 (87%) completed the corresponding PRO-CTCAE item list. We observed a prevalence (any grade) of more than 50% across 12 of the 19 symptomatic adverse events examined: fatigue (123 [87%] of 141 patients), decreased appetite (116 [83%] of 139 patients), insomnia (112 [79%] of 142 patients), chills (103 [73%] of 142 patients), diarrhoea (99 [70%] of 141 patients), sadness (81 [57%] of 141 patients), general pain (78 [55%] of 143 patients), dizziness (78 [55%] of 143 patients), joint pain (74 [52%] of 142 patients), muscle pain (73 [51%] of 143 patients), headache (73 [51%] of 143 patients), and impaired concentration (72 [51%] of 142 patients). Inspection of moderate to severe grades revealed that more than 30% of patients reported fatigue (78 [55%] of 141 patients), decreased appetite (74 [53%] of 139 patients), diarrhoea (63 [45%] of 141 patients), chills (49 [35%] of 142 patients), and insomnia (44 [31%] of 142 patients). Physicians frequently under-reported symptoms in their patients. For example, gastrointestinal symptoms were consistently under-reported, including difficulty swallowing (28 [78%] of 36 patients), decreased appetite (75 [77%] of 98 participants), nausea (43 [70%] of 61 participants), and diarrhoea (60 [71%] of 85 participants). Our findings could assist clinicians in delivering more targeted and timely supportive care interventions and might inform patients about anticipated symptoms during the early post-CAR T-cell infusion period. Moreover, the observed discrepancies between patient-reported and clinician-reported symptoms suggest that more systematic use of patient-reported outcome measures might provide complementary insights beyond those captured through clinician assessment. Fondazione GIMEMA Franco Mandelli Onlus and Novartis Farma Italy.

Human pluripotent stem cells (hPSCs) can be used as a scalable source of lymphocytes for adoptive cell therapies, contingent on the robust generation of definitive hematopoietic intermediates. Early WNT activation with CHIR99021 during mesoderm induction promoted the formation of KDR+ ALDH1A2+ mesoderm, which is essential for subsequent generation of T cells in a retinoic acid (RA)-dependent manner. Integrated scRNA-seq and ATAC-seq defined a WNT-dependent developmental trajectory from hPSCs to KDR+ ALDH1A2+ mesoderm. Gene regulatory network modeling predicted HDAC2 and E-box transcription factors as regulators of RA-responsive mesodermal differentiation downstream of WNT. HDAC2 knockout impaired, while HDAC2 overexpression enhanced KDR+ ALDH1A2+ mesoderm formation. E-box factor manipulation had no discernible effect. An orthogonal chemical screen confirmed that HDAC2 inhibition suppressed KDR+ ALDH1A2+ mesoderm, whereas modulating histone methylation enhanced their formation. These findings reveal mechanisms by which WNT signaling promotes RA-responsive mesoderm, and they suggest methods to improve the generation of lymphocytes from hPSCs.

Aging of the hematopoietic system has profound consequences for organismal health and longevity, attributed to the well-characterized functional aging of hematopoietic stem cells (HSCs). Here, we tested whether progenitor cells may demonstrate age resistance to enable hematopoietic homeostasis throughout life despite the functional decline of upstream HSCs. Strikingly, our results revealed unwavering reconstitution capacity by young and old progenitors, demonstrating that intermediate progenitors are functionally unaffected by aging and placing Flk2+ multipotent progenitors (MPPFs) as a potential source of age resilience. This unique finding was emphasized by unchanged transcriptomic, proliferation, and mitochondrial capacity of young and old MPPFs, revealing remarkable similarities upon aging. Considering that HSCs functionally decline with age, yet intermediate progenitors remain unperturbed and "age resilient", we posit that MPPFs may play an essential role in protecting downstream progenitors from inheriting age-related properties from HSCs. We propose three potential mechanisms for how MPPFs maintain hematopoietic integrity and homeostasis with age.

The International Prognostic Index (IPI) is an essential prognostic tool for patients with large B-cell lymphoma (LBCL). To compare outcomes after chimeric antigen receptor T-cell (CART) therapy and allogeneic stem cell transplantation (alloSCT) in relation to IPI risk factors, we analyzed 515 LBCL patients receiving CART (n = 303) or alloSCT (n = 212) as ≥third-line treatment, registered with EBMT (2016-2021). Patients treated with CART were older (median 62.4 vs 51.1 years), had higher IPI scores (48.2% vs 20.8% high/high-intermediate risk), and a higher incidence of refractory disease (84.1% vs 34.6%). At 24 months, overall survival (OS) was 49% vs 41%, progression-free survival (PFS) was 37% vs 32%, relapse-incidence (RI) was 56% vs 38%, and non-relapse-mortality (NRM) was 7% vs 30%, respectively. In multivariate analysis, CART therapy showed superior OS primarily due to significantly lower NRM, while RI was higher. The survival benefit of CART was significant in patients with low/low-intermediate IPI (OS HR 0.43, 95% CI 0.31-0.60), but not observed in high-risk patients. Elevated LDH eliminated the PFS advantage of CART over alloSCT. Poor outcomes after CART in patients with high-risk disease support early preparation for alloSCT for eligible patients.

Huntington's disease (HD) and ankylosing spondylitis (AS) are genetically and pathophysiologically distinct conditions, and their concurrent management may present a complex clinical challenge. A case is reported of a 35-year-old man with genetically confirmed HD and concurrently diagnosed AS, treated with autologous mesenchymal stem cell (MSC) therapy over three consecutive monthly sessions (50 million MSCs per session, total 150 million administered, intravenous and epidural routes). Validated disease-specific assessments were performed at each visit by the treating neurologist before the cell administration of that day: the Unified Huntington's Disease Rating Scale motor score (UHDRS motor), the Bath Ankylosing Spondylitis Functional Index (BASFI), and the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). Three serial assessments captured changes from baseline (cumulative dose 0) through cumulative doses of 50 million and 100 million MSCs, after which the third (final) dose was administered without subsequent reassessment. Over the two-month observation period, UHDRS motor score declined from 19 to 2, BASFI from 4.0 to 1.0 (with a transient increase to 8.5 at the second visit), and BASDAI from 2.0 to 1.0. No serious short-term adverse events were observed during the active treatment period. Given the single-patient design, concurrent pharmacotherapy, unblinded assessment, absence of objective biomarkers, and absence of post-third-dose assessment, causal attribution to MSC therapy cannot be established. The observation is presented as hypothesis-generating and warrants further investigation under controlled conditions.

Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome is a recently discovered acquired autoinflammatory disease caused by a point mutation in the UBA1 gene of myeloid progenitor cells. We present a case of an 81-year-old male with VEXAS syndrome. His manifestations included severe cutaneous symptoms, cytopenias, and other organ inflammation, which initially posed a significant diagnostic challenge, given that VEXAS syndrome had only recently been discovered at that time. Multiple therapies were trialed, including courses of antibiotics and immunomodulatory agents. The diagnosis was ultimately confirmed by bone marrow biopsy and genetic testing, with a positive UBA1 mutation with an allele frequency of 10% in the myeloid progenitor cell line. Symptom control was ultimately achieved with methotrexate and chronic prednisone at low-to-moderate doses. Unfortunately, he developed methotrexate-induced bone marrow toxicity, identified during a hospitalization for community-acquired pneumonia; thus, the methotrexate was discontinued. Shortly thereafter, he achieved not only resolution of his autoinflammatory symptoms and hematologic abnormalities, but also clearance of the UBA1 gene mutation. He has since tapered off prednisone entirely and remains in drug-free biochemical and symptomatic remission. This case raises questions about the possible role of higher-intensity initial treatment in the management of VEXAS syndrome to target the bone marrow. Such therapies could include agents that induce temporary myelosuppression with the goal of subsequent treatment-free remission. Furthermore, we hypothesize that his relatively low UBA1 allele frequency may serve as a diagnostic marker for an increased likelihood of remission.

Long-term culture of human embryonic stem cells (hESCs) often induces chromosomal abnormalities, which limits their clinical use. However, the underlying mechanisms are unclear. Early replication fragile sites (ERFSs) are genomic loci susceptible to breakage in early S-phase and serve as hotspots for chromosomal rearrangements, with established links to carcinogenesis. To map ERFSs in hESCs, we established the early S-phase synchronization protocols and identified ERFSs. These ERFSs are enriched in GC content and short interspersed nuclear elements (SINEs) and are frequently located in promoters or enhancers of genes involved in pluripotency, proliferation, and genomic stability. ERFSs also overlap with regions associated with copy number variants (CNVs) and single nucleotide variants (SNVs) linked to cancers. Furthermore, we found that chromatin accessibility contributes to ERFS formation. Collectively, these findings provide a key resource for advancing ERFS research, offering insights into the phenotypic and genomic alterations observed in long-term hESC cultures.

Physical function frequently declines after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, the influence of disease status and general condition at the time of transplantation on longitudinal functional changes remains unclear. This retrospective study included 135 adult patients with hematological malignancies who underwent their first allo-HSCT and completed physical function assessments before transplantation and at discharge. Handgrip strength and 6-min walk distance (6MWD) were evaluated. Patients were stratified according to disease status (complete remission [CR] vs. non-CR) and general condition (performance status [PS]). Both handgrip strength and 6MWD decreased significantly after transplantation in all groups. No significant differences in functional changes were observed between the CR and non-CR groups. In contrast, patients with poor PS at transplantation tended to show a greater decline in 6MWD than those with good PS. Multiple regression analysis identified PS at transplantation, age, sex, and change in the hemoglobin level as significant factors associated with changes in 6MWD. Pre-transplant PS was associated with a greater post-transplant decline in endurance capacity, regardless of disease status. PS may serve as a practical clinical indicator for identifying patients at higher risk of physical function deterioration and guiding early targeted rehabilitation interventions.