Hematopoietic System Research Articles

Genomic instability and genetic heterogeneity in aging: insights from clonal hematopoiesis (CHIP), monoclonal gammopathy (MGUS), and monoclonal B-cell lymphocytosis (MBL).

Aging is a multifaceted process characterized by a gradual decline in physiological function and increased susceptibility to a range of chronic diseases. Among the molecular and cellular mechanisms driving aging, genomic instability is a fundamental hallmark, contributing to increased mutation load and genetic heterogeneity within cellular populations. This review explores the role of genomic instability and genetic heterogeneity in aging in the hematopoietic system, with a particular focus on clonal hematopoiesis of indeterminate potential (CHIP), monoclonal gammopathy of undetermined significance (MGUS), and monoclonal B-cell lymphocytosis (MBL) as biomarkers. CHIP involves the clonal expansion of hematopoietic stem cells with somatic mutations. In contrast, MGUS is characterized by the presence of clonal plasma cells producing monoclonal immunoglobulins, while MBL is characterized by clonal proliferation of B cells. These conditions are prevalent in the aging population and serve as measurable indicators of underlying genomic instability. Studying these entities offers valuable insights into the mechanisms by which somatic mutations accumulate and drive clonal evolution in the hematopoietic system, providing a deeper understanding of how aging impacts cellular and tissue homeostasis. In summary, the hematopoietic system serves as a powerful model for investigating the interplay between genomic instability and aging. Incorporating age-related hematological conditions into aging research, alongside other biomarkers such as epigenetic clocks, can enhance the precision and predictive power of biological age assessments. These biomarkers provide a comprehensive view of the aging process, facilitating the early detection of age-related diseases and hopefully enabling personalized healthcare strategies.

Diagnosis of acute lymphoblastic leukaemia: an overview of the current genomic classification, diagnostic approaches, and future directions.

B-acute lymphoblastic leukaemia (B-ALL) is a haematological disease resulting from haematopoietic system dysfunction, leading to the unchecked growth of immature B lymphoblasts. The disease's complexity is underscored by the spectrum of genetic aberrations that underlie B-ALL entities, necessitating advanced genetic analyses for precise classification and risk determination. Prior to the adoption of next-generation sequencing into standard diagnostic practices, up to 30% of B-ALL cases were not assigned to specific entities due to the limitations of traditional diagnostic methods. The advent of comprehensive genomic analysis, especially whole-genome transcriptome sequencing, has significantly enhanced our understanding of B-ALL's molecular heterogeneity, paving the way for the exploration of novel, tailored treatment strategies. Furthermore, recent technological innovations, such as optical genome mapping, methylation profiling, and single-cell sequencing, have propelled forward the fields of cancer research and B-ALL management. These innovations introduce novel diagnostic approaches and prognostic markers, facilitating a deeper, more nuanced understanding of individual patient disease profiles. This review focuses on the latest diagnostic standards and assays for B-ALL, the importance of new technologies and biomarkers in enhancing diagnostic accuracy, and the expected role of innovative advancements in the future diagnosis and treatment of B-ALL.

Sparse inference of the human haematopoietic system from heterogeneous and partially observed genomic data

Abstract Haematopoiesis is the process of blood cells’ formation, with progenitor stem cells differentiating into mature forms such as white and red blood cells or platelets. While progenitor cells share regulatory pathways involving common nuclear factors, specific networks shape their fate towards particular lineages. This paper analyses the complex regulatory network that drives the formation of mature red blood cells and platelets from their common precursors. Using the latest reverse transcription quantitative real-time PCR genomic data, we develop a dedicated graphical model that incorporates the effect of external genomic data and allows inference of regulatory networks from the high-dimensional and partially observed data.

Evaluation of the chronic oral toxicity of the classical ancient prescription Kai-Xin-San

Ethnopharmacological relevanceThe Kai-Xin-San (KXS), as an ancient classic prescription, has been used for the treatment of amnesia for thousands of years. Modern clinical and non-clinical pharmacological studies have found that it has significant therapeutic effects on dementia and depression, but there are relatively few studies on its safety. Aim of the studySubacute and chronic toxicity studies were conducted to investigate the symptoms, severity, target organs, development and recovery of toxic reactions, as well as the toxic dose. These studies provide technical data for ensuring the safety of KXS. Materials and methodsIn the sub-acute toxicity study, rats were orally administered KXS at doses of 0.80, 1.61, 3.22, and 6.43 g/kg body weight for a duration of 4 weeks. In the chronic toxicity study, rats were orally administered KXS at doses of 0.27, 0.81, and 2.43 g/kg body weight for a duration of 26 weeks, and a withdrawal study was conducted for a period of 4 weeks after the treatment.The rats were observed daily for clinical signs and mortality. Changes in body weight, food consumption, and water consumption were periodically monitored. Additionally, urinalysis results, hematological and biochemical parameters, relative organ weights, and pathology were monitored at specific observation time points. ResultsIn the sub-acute toxicity study, necropsy of dead and moribund rats revealed evident distension and swelling of the gastrointestinal tract, as well as thinning of the intestinal wall. The main adverse reactions observed included flatulence, piloerection, abnormal breathing sounds, and emaciation. Doses of 1.61 g/kg and below did not cause animal death. The gastrointestinal system is the main target organ of toxicity. In the chronic toxicity study, the no-observed-adverse-effect-level (NOAEL) of KXS was 0.27 g/kg, and its toxic effects were primarily concentrated in the gastrointestinal system. This led to secondary pathological changes in the immune system, hematopoietic system, and heart, suggesting that relevant indicators should be monitored when large doses are used clinically for an extended period of time. ConclusionsDuring the rodent toxicity evaluation, severe gastrointestinal damage was observed when KXS, powdered with crude drugs, was administered. The NOAEL for rats was found to be 0.27 g/kg/day.

Mesenchymal stromal cells surface engineering for efficient hematopoietic reconstitution

Mesenchymal stromal cells (MSCs) are believed to migrate to injury sites, release chemical attractants, and either recruit local stem cells or modulate the immune system positively. Although MSCs are highly desired for their potential to reduce inflammation and promote tissue regeneration, their limited lifespan restricts their applications. This study presents a simple approach for protecting MSCs with epigallocatechin-3-gallate (EGCG) and magnesium (Mg) based metal-organic framework coatings (E-Mg@MSC). The layer strengthens MSCs resistant to harmful stresses and creates a favorable microenvironment for repair by providing Mg to facilitate MSCs' osteogenic differentiation and using EGCG to neutralize excessive reactive oxygen species (ROS). E-Mg@MSC serves as a treatment for hematopoietic injury induced by ionizing radiation (IR). Coated MSCs exhibit sustained secretion of hematopoietic growth factors and precise homing to radiation-sensitive tissues. In vivo studies show substantial enhancement in hematopoietic system recovery and multi-organ protection. Mechanistic investigations suggest that E-Mg@MSC mitigates IR-induced ROS, cell apoptosis, and ferroptosis, contributing to reduced radiation damage. The system represents a versatile and compelling strategy for cell-surface engineering with functional materials to advance MSCs therapy.

Failure of metabolic checkpoint control during late-stage granulopoiesis drives neutropenia in reticular dysgenesis

AbstractCellular metabolism is highly dynamic during hematopoiesis, yet the regulatory networks that maintain metabolic homeostasis during differentiation are incompletely understood. Herein, we have studied the grave immunodeficiency syndrome reticular dysgenesis caused by loss of mitochondrial adenylate kinase 2 (AK2) function. By coupling single-cell transcriptomics in samples from patients with reticular dysgenesis with a CRISPR model of this disorder in primary human hematopoietic stem cells, we found that the consequences of AK2 deficiency for the hematopoietic system are contingent on the effective engagement of metabolic checkpoints. In hematopoietic stem and progenitor cells, including early granulocyte precursors, AK2 deficiency reduced mechanistic target of rapamycin (mTOR) signaling and anabolic pathway activation. This conserved nutrient homeostasis and maintained cell survival and proliferation. In contrast, during late-stage granulopoiesis, metabolic checkpoints were ineffective, leading to a paradoxical upregulation of mTOR activity and energy-consuming anabolic pathways such as ribonucleoprotein synthesis in AK2-deficient cells. This caused nucleotide imbalance, including highly elevated adenosine monophosphate and inosine monophosphate levels, the depletion of essential substrates such as NAD+ and aspartate, and ultimately resulted in proliferation arrest and demise of the granulocyte lineage. Our findings suggest that even severe metabolic defects can be tolerated with the help of metabolic checkpoints but that the failure of such checkpoints in differentiated cells results in a catastrophic loss of homeostasis.

Blood-generating heart-forming organoids recapitulate co-development of the human haematopoietic system and the embryonic heart.

Despite the biomedical importance of haematopoietic stem cells and haematopoietic progenitor cells, their in vitro stabilization in a developmental context has not been achieved due to limited knowledge of signals and markers specifying the multiple haematopoietic waves as well as ethically restricted access to the human embryo. Thus, an in vitro approach resembling aspects of haematopoietic development in the context of neighbouring tissues is of interest. Our established human pluripotent stem cell-derived heart-forming organoids (HFOs) recapitulate aspects of heart, vasculature and foregut co-development. Modulating HFO differentiation, we here report the generation of blood-generating HFOs. While maintaining a functional ventricular-like heart anlagen, blood-generating HFOs comprise a mesenchyme-embedded haemogenic endothelial layer encompassing multiple haematopoietic derivatives and haematopoietic progenitor cells with erythro-myeloid and lymphoid potential, reflecting aspects of primitive and definitive haematopoiesis. The model enables the morphologically structured co-development of cardiac, endothelial and multipotent haematopoietic tissues equivalent to the intra-embryonic haematopoietic region in vivo, promoting research on haematopoiesis in vitro.

Proteomic analysis of HeLa cells after stable transfection with the Chlamydia trachomatis CT143 gene

BackgroundThe CT143 protein of Chlamydia trachomatis (Ct) is a key immunodominant antigen and candidate type-III secretion substrate. Although CT143 expression has not been detected in the cytosol of infected cells, it is known to interfere with the physiological behavior of HeLa cells. This study aims to investigate how the CT143 protein affects the protein expression profile of HeLa cells, providing a basis for further research into Ct’s pathogenic mechanisms. MethodsWe constructed a stably transfected HeLa cell line, pCD513B-1-CT143-HeLa, and a control cell line, pCD513B-1-HeLa. Protein expression profiles of these cell lines were determined using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Differentially expressed proteins were identified, constructed into a database, and verified using parallel reaction monitoring (PRM). Bioinformatics software facilitated the preliminary analysis of the biological functions of these differential proteins. ResultsA total of 221 host proteins were differentially expressed, with 68 upregulated and 153 downregulated. These variations influence the regulation of peptidase activity and are crucial in biological processes such as cell secretion and protease activity. Significant changes were noted in protein processing, alcohol dehydrogenase activity, Aldo-Keto reductase activity, and peptidase regulator activity. Furthermore, alterations were observed in cellular components like the plasma membrane and cell periphery. Pathways involving the hematopoietic system, glycosaminoglycan degradation, retinol metabolism, and cytochrome P450-mediated exogenous drug metabolism were notably affected. Indirect interactions among differentially expressed proteins included three key nodal proteins: C3, IFIT3, and IFIT1. ConclusionThe successful construction of a host differential protein expression profile was achieved through stable transfection of HeLa cells with the CT143 gene. The differential proteins identified are implicated in regulating various biological processes such as intracellular signal transduction, cell secretion, protein processing, hydrolysis, and enzyme activity. These findings suggest that the CT143 protein may influence the host cell’s biological behavior by altering host protein expression, potentially hindering Ct growth and development.

Early developmental anomalies in zebrafish (Danio rerio) embryos induced by the Clematis florida Thunb.

Ethnopharmacological relevanceThe C.florida. is one of the common medicines used by She population in China, with therapeutic effects of promoting blood circulation and anti-inflammatory. According to the acute toxicity grading standard of chemical substances, this herb is a low-toxicity herb. At present, the safety of C.florida., especially its impact on early embryonic development, is still unclear. Aim of the studyThis study investigated the toxic effects of C. florida. on early embryonic development using a zebrafish embryo model. Materials and methodsIn this study, we used zebrafish embryos exposed to C.florida. at early stage to assess the early developmental toxicity by analyzing the developmental toxicity phenotype, oxidative stress, cell apoptosis, total enzyme activity, behavioral trajectory, and gene expression levels. ResultsEmbryos of the zebrafish exposed to different concentrations of C.florida. exhibited multiple organs and systems developmental disorders, including the heart, vessels, brain, bone, liver, and so on. Especially, with the increase of drug concentration, it is observed that the developmental malformations of the cardiovascular structure and function in larvae are becoming increasingly severe. In addition, results show that the abnormalities in embryonic development may be attributed to oxidative stress induced by apoptosis and activation of immune system resulting from an imbalance in the hematopoietic system. ConclusionsThis study provides a comprehensive and detailed summary of the toxic effects of C.florida. on embryonic development, which contributes to a deeper understanding of the potential adverse developmental consequences, and also prompt people to pay considerable attention to its treatment in medicinal practice.

New insights into the endothelial origin of hematopoietic system inspired by "TIF" approaches.

Hematopoietic stem progenitor cells (HSPCs) are derived from a specialized subset of endothelial cells named hemogenic endothelial cells (HECs) via a process of endothelial-to-hematopoietic transition during embryogenesis. Recently, with the usage of multiple single-cell technologies and advanced genetic lineage tracing techniques, namely, "TIF" approaches that combining transcriptome, immunophenotype and function/fate analyses, massive new insights have been achieved regarding the cellular and molecular evolution underlying the emergence of HSPCs from embryonic vascular beds. In this review, we focus on the most recent advances in the enrichment markers, functional characteristics, developmental paths, molecular controls, and the embryonic site-relevance of the key intermediate cell populations bridging embryonic vascular and hematopoietic systems, namely HECs and pre-hematopoietic stem cells, the immediate progenies of some HECs, in mouse and human embryos. Specifically, using expression analyses at both transcriptional and protein levels and especially efficient functional assays, we propose that the onset of Kit expression is at the HEC stage, which has previously been controversial.

Effect of Tumor Suppressor Gene Kmt2c Heterozygous Deletion on Hematopoietic System in Mice

To explore the effect of heterozygous deletion of histone methyltransferase Kmt2c gene on the hematological system of mice. CRISPR/Cas9 technology was used to construct mice model of Kmt2c heterozygous deletion (Kmt2c+/-) and the changes of whole blood cell count in mice were continuously monitored by blood routine test. The clonal expansion ability of bone marrow cells was explored by colony formation assay in vitro and the proportion of primitive hematopoietic cells, including long-term hematopoietic stem cell (LT-HSC), short-term hematopoietic stem cell (ST-HSC), and multipotent progenitor cell in mutant mice was analyzed by flow cytometry. Kmt2c+/- mice model was successfully constructed, and the mRNA expression level of Kmt2c was 28% of that of C57BL/6J mice. The colony formation ability of bone marrow cells of Kmt2c+/- mice in vitro increased with the passage times, and the colony number in the fourth generation was significantly higher than that of control group (P <0.05). The proportions of LT-HSC and ST-HSC in the primitive hematopoietic cell population of Kmt2c+/- mice was 19.6%±3.3% and 28.9%±4.9%, respectively, which showed an increasing trend compared with 16.9%±2.6% and 18.9%±2.5% in control group, but the difference was not statistically significant (P >0.05). The white blood cell count of Kmt2c+/- mice gradually increased after 12 weeks of monitoring and reached (9.8±1.0)×109/L at the 14th week, which was significantly higher than (7.3±1.4)×109/L of control group (P < 0.05). The bone marrow cells of Kmt2c+/- mice have potential of clonal expansion.

A DESCRIPTIVE STUDY TO ASSESS KNOWLEDGE REGARDING UMBILICAL CORD BLOOD BANKING AMONG WOMEN IN THE REPRODUCTIVE AGE

Umbilical cord blood stem cells are the name given to the blood remaining in the umbilical cord and placenta after childbirth. Umbilical cord blood has the potential to be a huge source of primitive hematopoietic stem and progenitor cells that can be used to reconstruct the hematopoietic system and restore immunological function in individuals who require treatment. A descriptive research methodology was adopted in this study and 100 reproductive age group women in Sharda Hospital were selected in the present study. Convenience sampling technique was adopted for the data collection. The information was gathered via a knowledge questionnaire, which was used to assess knowledge regarding umbilical cord blood banking. The result revealed that 30 women had poor knowledge, 63 women had moderate knowledge and 7 had knowledge about umbilical cord blood banking. The importance of umbilical cord blood banking information was given among selected 100 participating women via the help of a pamphlet to raise awareness of uses of umbilical cord bloodbanking.

Evaluation of Immuno-Hematological Parameters of Severe and Mild COVID-19 Cases in Babylon Province, Iraq

The hematopoietic system plays a very important role in contracting the corona virus infection. Hematology indicators are among the factors related to the clinical results of patients with covid-19 due to their cost-effectiveness, availability, speed and convenience of testing. The aim of this study was comparing hematological parameters including the number of Red Blood Cells (RBC), hemoglobin, hematocrit, and platelet count among mild and severe COVID-19 patients. Methods: The study was conducted on 100 Iraqi patients COVID-19 patients. Subjects were classified into two groups with mild (n= 50) and severe (n=50) COVID-19 infection symptoms based on the clinical criteria. The hematological parameters measurement included Red Blood Cell (RBC) count, Hemoglobin (Hb) levels, White Blood Cell (WBC) count, Platelet count (PLT), Hematocrit (HCT) levels, Platelet Distribution Width (PDW), and Mean Platelet Volume (MPV). An independent sample T-test was used to compare the means of hematological parameters between two groups. Results: The RBC count was significantly lower in severe group compared to mild group (P ≤ 0.05). HCT levels were significantly reduced in the severe group compared to mild group (P ≤ 0.05). The severe patients had a significantly lower PLT than mild patients (P ≤ 0.05). No significant difference in Hb levels was observed between severe and mild patients. The severe patients had a significantly higher PDW than mild patients (P ≤ 0.05). Additionally, the severe patients had a significantly higher MPV than mild patients (P ≤ 0.05). Conclusion: The findings of this study indicate that complete blood count measurements can be used as useful biomarkers to assess the severity of Covid-19. Early identification of severe COVID-19 patients using these markers can help to better manage and accelerate the treatment process for COVID-19 patients.

Obesity modulates hematopoietic stem cell fate decision via IL-1β induced p38/MAPK signaling pathway

BackgroundObesity is accompanied by inflammation, which significantly affects the homeostasis of the immune microenvironment. Hematopoietic stem cells (HSCs), residing primarily in the bone marrow, play a vital role in maintaining and producing diverse mature blood cell lineages for the adult hematopoietic and immune systems. However, how HSCs development is affected by obese-promoting inflammation, and the mechanism by which HSC hematopoietic potency is affected by inflammatory signals originating from the obese-promoting changes on bone marrow niche remain unclear. This study elucidates the relationship between obesity-promoting inflammation and HSC fate determination.MethodsThe obesity mice model was established by feeding C57BL/6J mice a high-fat diet (HFD) containing 60% kcal fat. After 6 weeks, HSCs were analyzed using flow cytometry and identified key inflammation cytokine. Transcriptome sequencing techniques were used to discern the distinct pathways in HSCs. Ultimately, confirming the biological mechanism of obesity-induced HSC fate changes via Anakinra blocking specific inflammatory signals.ResultsObesity caused by HFD changed the physical and biochemical properties of the bone marrow niche. In the HFD mice, the population of long-term HSCs in the bone marrow was decreased and facilitated HSCs differentiation towards the myeloid lineage. In addition, HFD increased expression of the inflammatory factor IL-1β in the bone marrow, and a significantly increased expression of IL-1r1 and active p38/MAPK signaling pathway were detected in the HSCs. Inhibition of IL-1β further normalized the expression of genes in p38/MAPK pathway and reversed HSC fate.ConclusionsThese findings have been demonstrated that the p38/MAPK signaling pathway in HSCs is activated by elevated levels of IL-1β within the HSC niche in obese models, thereby regulating HSC differentiation. It suggested a direct link between obesity-promoting inflammation and myeloid differentiation bias of HSCs in the HFD mice.Graphical abstract

Polycythemia under Clozapine: A Case Study

Clozapine is widely recognized as a last-resort treatment for resistant schizophrenia, due to its efficacy in reducing persistent symptoms and lowering the risk of suicidal behavior. However, its use is limited by severe side effects, including hematological complications such as agranulocytosis. A less documented but significant complication is clozapine-induced polycythemia. This case study explores the development of polycythemia in a patient undergoing clozapine treatment for refractory schizophrenia. Despite the reduction of clozapine doses, polycythemia persisted, necessitating continued treatment due to the lack of alternative therapeutic options. The patient’s hematological abnormalities were managed through regular phlebotomies, and close collaboration between psychiatric and hematological services. This case emphasizes the importance of rigorous hematological monitoring in patients on clozapine and calls for further research into its effects on the hematopoietic system, particularly concerning polycythemia. The mechanisms underlying this association are not well understood but may involve immune-mediated responses, bone marrow alterations, and metabolic changes, necessitating multidisciplinary management for optimal patient care.

Evaluation of disease activity in systemic lupus erythematosus using standard deviation of lymphocyte volume combined with red blood cell count and lymphocyte percentage

Systemic lupus erythematosus (SLE) commonly damages the blood system and often manifests as blood cell abnormalities. The performance of biomarkers for predicting SLE activity still requires further improvement. This study aimed to analyze blood cell parameters to identify key indicators for a SLE activity prediction model. Clinical data of 138 patients with SLE (high activity, n = 40; moderate activity, n = 44; mild activity, n = 37; low activity, n = 17) and 100 healthy controls (HCs) were retrospectively analyzed. Data from 89 paired admission–discharge patients with SLE were collected. Differences and associations between blood cell parameters and disease indicators, as well as the relationship between the these parameters and organ damage, were examined. Machine-learning methods were employed to develop a prediction model for disease activity evaluation. Most blood cell parameters (22/26, 84.62%) differed significantly between patients with SLE and HCs. Analysis of 89 paired patients with SLE revealed significant changes in most blood cell parameters at discharge. The standard deviation of lymphocyte volume (SD-V-LY), red blood cell (RBC) count, lymphocyte percentage (LY%), hemoglobin(HGB), hematocrit(HCT), and neutrophil percentage(NE%) correlated with disease activity. By employing machine learning, an optimal model was established to predict active SLE using SD-V-LY, RBC count, and LY% (area under the curve [AUC] = 0.908, sensitivity = 0.811). External validation indicated impressive performance (AUC = 0.940, sensitivity = 0.833). Correlation analysis revealed that SD-V-LY was positively correlated with ESR, IgG, IgA, and IgM but was negatively correlated with C3 and C4. The RBC count was linked to renal and hematopoietic system impairments, whereas LY% was associated with joint/muscle involvement. In conclusion, SD-V-LY is associated with SLE disease activity. SD-V-LY combined with RBC count and LY% contributes to a prediction model, which can be utilized as an effective tool for assessing SLE activity.

Impacts of X-Ray irradiation on RBC, WBC and PLT by low doses (40kV and 80kV).

This study aimed to assess the impact of irradiation on red blood cells (RBCs), white blood cells (WBCs), and platelets (PLTs) using modest doses of X-ray radiation (40 kV and 80 kV). The blood samples were exposed to X-ray irradiation at 40 and 80 kV. A haematology analyzer system with automated capability was used to quantify cellular components, specifically WBCs, RBCs, and PLTs, both before and after exposure to radiation. The study found that irradiation reduced WBC and PLT numbers. When exposed to 40 kV and 80 kV voltages, the WBC and PLT improved statistically significantly (p = 0.001). Nonetheless, the statistical analysis revealed no statistically significant difference (p > 0.05) in red blood cell count between 40 and 80 kV doses. It can be concluded that the haematopoietic system exhibits a high degree of sensitivity to radiation exposure.

Essential role of Dhx16-mediated ribosome assembly in maintenance of hematopoietic stem cells.

Hematopoietic stem cells (HSCs) are vital for the differentiation of all mature blood cells, with their homeostasis being tightly regulated by intrinsic and extrinsic factors. Alternative splicing, mediated by the spliceosome complex, plays a crucial role in regulating HSC homeostasis by increasing protein diversity. This study focuses on the ATP-dependent RNA helicase DHX16, a key spliceosome component, and its role in HSC regulation. Using conditional knockout mice, we demonstrate that loss of Dhx16 in the hematopoietic system results in significant depletion of hematopoietic stem and progenitor cells, bone marrow failure, and rapid mortality. Dhx16-deficient HSCs exhibit impaired quiescence, G2-M phase cell cycle arrest, reduced protein synthesis, abnormal ribosome assembly, increased apoptosis, and decreased self-renewal capacity. Multi-omics analysis identified intron 4 retention in Emg1 mRNA in Dhx16 knockout HSCs, leading to reduced EMG1 protein expression, disrupted ribosome assembly, and nucleolar stress, activating the p53 pathway. Overexpression of Emg1 in Dhx16-deficient HSCs partially restored ribosome assembly and HSC function, suggesting Emg1 as a potential therapeutic target for ribosomopathies. Our findings reveal the critical role of Dhx16 in HSC homeostasis through the regulation of alternative splicing and ribosome assembly, providing insights into the molecular mechanisms underlying hematopoietic diseases and potential therapeutic strategies.

Radiation protection of sodium alginate and its regulatory effect on intestinal microflora in mice

Prolonged or high-dose exposure to ionizing radiation (IR) can cause damage to normal tissues of the body. Therefore, it is imperative to find effective radiation protective agents to mitigate IR-induced damage. This study evaluated the effects of sodium alginate (SA) on the radiation protection and modulatory effects of gut microorganisms using a 60Coγ-induced damage model in mice. Results showed that SA could reduce the damage of hematopoietic system; and alleviate the oxidative damage in irradiated mice by inhibiting the content of malondialdehyde (MDA) and increasing the activities of superoxide dismutase (SOD) and glutathione (GSH) in serum, spleen, jejunum and liver. Moreover, SA treatment ameliorated IR-induced small intestine lesions and alleviated liver injury. This was consistent with decreased levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and tumor necrosis factor-α (TNF-α), and increased levels of interferon-γ (IFN-γ) and interleukin-2 (IL-2) after SA treatment. Furthermore, SA treatment reversed IR-induced gut dysbiosis, elevated the Firmicutes/Bacteroidetes ratio, increased the beneficial bacteria and reduced the pathogenic bacteria in the small intestine. In conclusion, the present study demonstrated that SA exerted good radioprotective effect by improving hematopoietic system, alleviating oxidative stress, attenuating liver injury and inflammatory response, and modulating the intestinal microbiota in irradiated mice.

Deciphering Transcriptomic Variations in Hematopoietic Lineages: HSCs, EBs, and MKs.

In the realm of hematopoiesis, hematopoietic stem cells (HSCs) serve as pivotal entities responsible for generating various blood cell types, initiating both the myeloid and lymphoid branches within the hematopoietic lineage. This intricate process is marked by genetic variations that underscore the crucial role of genes in regulating cellular functions and interactions. Recognizing the significance of genetic factors in this context, this article delves into a genetic perspective, aiming to unravel the biological factors that govern the transition from one cell's fate to another within the hematopoietic system. To gain deeper insights into the genetic traits of three distinct blood cell types-HSCs, erythroblasts (EBs), and megakaryocytes (MKs)-we conducted a comprehensive transcriptomic analysis. Leveraging diverse hematopoietic cell datasets from healthy individuals, sourced from The BLUEPRINT consortium, our investigation targeted the identification of genetic variants responsible for changes in gene expression levels and epigenetic modifications across the entire human genome in each of these cell types. The total number of normalized expressed transcripts includes 14,233 novel trinity lncRNAs, 13,749 mRNAs, and 3092 lncRNAs. This scrutiny revealed a total of 31,074 transcripts, with a notable revelation that 14,233 of them were previously unidentified or novel lncRNAs, highlighting a substantial reservoir of genetic information yet to be explored. Examining their expression across distinct lineages further unveiled 2845 differentially expressed (DE) mRNAs and 354 DE long noncoding RNAs (lncRNAs) notably enriched among the three distinct blood cell types: HSCs, EBs, and MKs. Our investigation extended beyond mRNA to focus on the dynamic expression of lncRNAs, revealing a well-defined pattern that played a significant role in regulating differentiation and cell-fate specification. This coordination of lncRNA dynamics extended to aberrations in both mRNA and lncRNA transcriptomes within HSCs, EBs, and MKs. We specifically characterized lncRNAs with preferential expression in HSCs, as well as in various downstream differentiated lineage progenitors of EBs and MKs, providing a comprehensive perspective on lncRNAs in human hematopoietic cells. Notably, the expression of lncRNAs exhibited substantial cell-to-cell variation, a phenomenon discernible only through single-cell analysis. The comparative analysis undertaken in this study provides valuable insights into the distinctive genetic signatures guiding the differentiation of these crucial hematopoietic cell types.