BFU-E

Diamond-Blackfan anemia (DBA) was the first ribosomopathy described in humans. DBA is a congenital hypoplastic anemia, characterized by macrocytic aregenerative anemia, manifesting by differentiation blockage between the BFU-e/CFU-e developmental erythroid progenitor stages. In 50 % of the DBA cases, various malformations are noted. Strikingly, for a hematological disease with a relative erythroid tropism, DBA is due to ribosomal haploinsufficiency in 24 different ribosomal protein (RP) genes. A few other genes have been described in DBA-like disorders, but they do not fit into the classical DBA phenotype (Sankaran et al...

BACKGROUND: Induction with daratumumab-based regimens followed by autologous stem cell transplantation is the current standard for newly diagnosed multiple myeloma (NDMM) patients eligible for intensive chemotherapy. However, concerns emerged regarding potential negative effects following daratumumab-based treatment on CD34+ mobilization. We here compared CD34+ mobilization and clonogenic potential between daratumumab and non-daratumumab based therapy without upfront plerixafor administration among patients affected by NDMM...

Recombinant human erythropoietin (rHuEPO) is a prevalent treatment for anemia in patients with chronic kidney disease. However, up to 10% of these patients exhibit EPO resistance or hyporesponsiveness, which may be caused by the depletion of erythroid progenitor cells. Thrombopoietin (TPO) has the potential to promote the growth of early progenitor cells and correct the depletion. In this study, we investigate the efficacy and the underlying mechanism of the combination therapy of TPO and EPO to EPO resistance...

Techniques allowing the long-term culture of the burst-forming unit of erythroid (BFU-E) progenitor cells are essential for understanding erythropoiesis. Here, we present a protocol for sorting mouse BFU-E cells and culturing them in a medium that promotes BFU-E cell expansion. We describe steps for isolating BFU-E cells from mouse fetal livers by combining magnetic microbeads with flow cytometry and culturing BFU-E cells with a specific expansion media. This approach can enhance the production of BFU-E cells...

Background: Severe trauma and hemorrhagic shock lead to persistent anemia. Although biologic gender is known to modulate inflammatory responses after critical illness, the impact of gender on anemia recovery after injury remains unknown. The aim of this study was to identify gender-specific differences in anemia recovery after critical illness. Materials and Methods: Male and proestrus female Sprague-Dawley rats (n = 8-9 per group) were subjected to lung contusion and hemorrhagic shock (LCHS) or LCHS with daily chronic stress (LCHS/CS) compared with naïve...

INTRODUCTION: Pneumonia is a common complication after severe trauma that is associated with worse outcomes with increased mortality. Critically ill trauma patients also have persistent inflammation and bone marrow dysfunction that manifests as persistent anemia. Terminal erythropoiesis, which occurs in bone marrow structures called erythroblastic islands (EBIs), has been shown to be impacted by trauma. Using a preclinical model of polytrauma and pneumonia, we sought to determine the effect of infection on bone marrow dysfunction and terminal erythropoiesis...

Today cord blood (CB) is a valuable source of hematopoietic stem cells to treat many hematological disorders. One of the limitations of CB utilization is the reduced number of nucleated cells including stem cells. Therefore, CB banks around the world have developed strategies in an attempt to improve donor selection and the quality of the CB inventory. This study aimed to determine the impact of passive smoking and caffeine consumption on CB quality. CBs were obtained from mothers who gave birth at King Abdulaziz Medical City...

Red blood cells supply the oxygen required for all human cells and are in demand for emerging blood-loss therapy. Here we identified N6-methyl-2'-deoxyadenosine (6mdA) as an agonist that promotes the hyperproliferation of burst-forming unit erythroid (BFU-E) progenitor cells. In addition, 6mdA represses the apoptosis of erythroid progenitor cells (EPCs). Combined use of with SCF and EPO enabled cultures of isolated BFU-E to be expanded up to 5,000-fold. Transcriptome analysis showed that 6mdA upregulates the expression of the EPC-associated factors c-Kit, Myb, and Gata2 and downregulates that of the erythroid maturation-related transcription factors Gata1, Spi1, and Klf1...

BACKGROUND: Sickle cell disease (SCD) is a highly prevalent genetic disease caused by a point mutation in the HBB gene, which can lead to chronic hemolytic anemia and vaso-occlusive events. Patient-derived induced pluripotent stem cells (iPSCs) hold promise for the development of novel predictive methods for screening drugs with anti-sickling activity. In this study, we evaluated and compared the efficiency of 2D and 3D erythroid differentiation protocols using a healthy control and SCD-iPSCs...

OBJECTIVE: To investigate the effect and relative mechanism of Recombinant Human Thrombopoietin (rhTPO) on long-term hematopoietic recovery in mice with acute radiation sickness. METHODS: Mice were intramuscularly injected with rhTPO (100 μg/kg) 2 hours after total body irradiation with 60 Co γ-rays (6.5 Gy). Moreover, six months after irradiation, peripheral blood, hematopoietic stem cells (HSC) ratio, competitive transplantation survival rate and chimerization rate, senescence rate of c-kit+ HSC, and p16 and p38 mRNA expression of c-kit+ HSC were detected...

BACKGROUND: Severe trauma disrupts bone marrow function resulting in persistent anemia and immunosuppression. Exosomes are extracellular vesicles implicated in disease, cellular functions, and immunomodulation. The effects of trauma plasma-derived exosomes on bone marrow hematopoiesis are unstudied; we hypothesized that trauma plasma-derived exosomes suppress bone marrow hematopoietic progenitor cell (HPC) growth and contribute to increased inflammatory cytokines and HPC mobilization...

BACKGROUND: The Jr blood group system includes a single, high-prevalence antigen, Jra , encoded by the ABCG2 gene. The impact of anti-Jra in pregnancy is variable, ranging from no clinical effect to severe anemia including some fetal deaths. Case reports have postulated that anti-Jra mediated fetal anemia is poorly hemolytic, suggesting other mechanisms of anemia may be involved. STUDY DESIGN AND METHODS: We describe the case of severe anti-Jra mediated fetal anemia...

Chronic kidney disease (CKD) is a global health condition characterized by a progressive deterioration of kidney function. It is associated with high serum levels of uremic toxins (UT), such as Indoxyl Sulfate (IS), which may participate in the genesis of several uremic complications. Anemia is one of the major complications in CKD patients that contribute to cardiovascular disease, increase morbi-mortality, and is associated with a deterioration of kidney failure in these patients. Our study aimed to characterize the impact of IS on CKD-related erythropoiesis...

Microgravity is known negatively affect physiology of living beings, including hematopoiesis. Dysregulation of hematopoietic cells and supporting stroma relationships in bone marrow niche may be in charge. We compared the efficacy of ex vivo expansion of hematopoietic stem and progenitor cells (HSPCs) in presence of native or osteocommitted MSCs under simulated microgravity (Smg) using Random Positioning Machine (RPM). In comparison with 1 g, a decrease of MSC-associated HSPCs and an increase of floating HSPCs was observed after 7 days of Smg exposure...

OBJECTIVE: To investigate the hematopoietic protective effect of platelet-derived growth factor (PDGF)-BB on radiation-induced myelosuppression model mice and effect of anti-apoptosis of megakaryocyte line Meg-01 cells, and its possible mechanism. METHODS: Mice were radiated with 4 Gy of 137 Csγ ray to establish the model of myelosuppression. Mice were weighed and peripheral blood cell were counted before radiation (day 0) and day 7, 14 and 21 after radiation...

OBJECTIVE: To explore the hematopoiesis protection effect of Danggui Buxue Tang (DBT) and its main components Angelica polysaccharide (APS) and Astragalus polysaccharide (ASPS) on myelosuppression mice, and the mechanism of anti-apoptosis of Meg-01 cells. METHODS: Mice were radiated with 4 Gy of 137 Csγ ray to establish the model of radiation-induced myelosuppression. DBT, APS or ASPS (10 mg/kg) were injected into irradiated mice. Peripheral blood cell counts were performed on mice before radiation (day 0) and day 7, 14 and 21 after radiation...

Infection caused by extracellular single-celled trypanosomes triggers a lethal chronic wasting disease in livestock and game animals. Through screening of 10 Trypanosoma evansi field isolates, exhibiting different levels of virulence in mice, the current study identifies an experimental disease model in which infection can last well over 100 days, mimicking the major features of chronic animal trypanosomosis. In this model, despite the well-controlled parasitemia, infection is hallmarked by severe trypanosomosis-associated pathology...

Early erythroid progenitors were originally defined by their colony-forming potential in vitro and classified into burst-forming and colony-forming "units" known as BFU-e and CFU-e. Until recently, methods for the direct prospective and complete isolation of pure BFU-e and CFU-e progenitors from freshly isolated adult mouse bone marrow were not available. To address this gap, a single-cell RNA-seq (scRNAseq) dataset of mouse bone marrow was analyzed for the expression of genes coding for cell surface markers...

The RNA exosome complex (EC) post-transcriptionally and co-transcriptionally processes and degrades RNAs in a context-dependent manner. Although the EC functions in diverse cell types, its contributions to stem and progenitor cell development are not well understood. Previously, we demonstrated that the transcriptional regulator of erythrocyte development GATA1 represses EC subunit genes, and the EC maintains erythroid progenitors in vitro. To determine if this mechanism operates in vivo, we utilized the hematopoietic-specific Vav1-Cre and "Conditional Inversion" (Coin = C) mouse system to ablate Exosc3, encoding an EC structural subunit...

Background: Dietary restriction has a profound effect in altering immune system and promoting metabolic health and aging. However, how dietary restriction impacts erythroid system is largely unknown. We found that a short-term caloric restriction (CR) stimulates expression of KLF1, a master regulator of erythroid development, in the spleen of mouse, and thus explored the potential effect of CR on erythropoiesis. Methods: We analyzed the effects of intermittent CR and continuous CR for different lengths of time on parameters of peripheral blood and erythroid profiles in the spleen and bone marrow in C57BL/6 mice...