BCL11A, a zinc finger repressor, is a stage-specific transcription factor that controls the switch from fetal (HbF, αγ) to adult (HbA, αβ) hemoglobin in erythroid cells. While BCL11A was known as a factor critical for B-lymphoid cell development, its relationship to erythroid cells and HbF arose through genome-wide association studies (GWAS). Subsequent work validated its role as a silencer of γ-globin gene expression in cultured cells and mice. Erythroid-specific loss of BCL11A rescues the phenotype of engineered sickle cell disease (SCD) mice, thereby suggesting that downregulation of BCL11A expression might be beneficial in patients with SCD and β-thalassemia. Common genetic variation in GWAS resides in an erythroid-specific enhancer within the BCL11A gene that is required for its own expression. CRISPR/Cas9 gene editing of the enhancer revealed a GATA-binding site that confers a large portion of its regulatory function. Disruption of the GATA site leads to robust HbF reactivation. Advancement of a guide RNA targeting the GATA-binding site in clinical trials has recently led to approval of first-in-man use of ex vivo CRISPR editing of hematopoietic stem/progenitor cells (HSPCs) as therapy of SCD and β-thalassemia. Future challenges include expanding access and infrastructure for delivery of genetic therapy to eligible patients, reducing potential toxicity and costs, exploring prospects for in vivo targeting of hematopoietic stem cells (HSCs), and developing small molecule drugs that impair function of BCL11A protein as an alternative option.
Visual analysis of peripheral blood smear slides using medical image analysis is required to diagnose red blood cell (RBC) morphological deformities caused by anemia. The absence of a complete anaemic RBC dataset has hindered the training and testing of deep convolutional neural networks (CNNs) for computer-aided analysis of RBC morphology. We introduce a benchmark RBC image dataset named Anemic RBC (AneRBC) to overcome this problem.
Hyperbaric oxygen (HBO) therapy has emerged as a potential treatment, shown to enhance blood flow and angiogenesis. However, specific effects and mechanisms of HBO on limb ischaemia responding to a hypoxic environment remain largely unknown. We aimed to investigate the therapeutic potential of HBO in the treatment of limb ischaemia.
Background: Oxidative stress and microglial activation are critical pathomechanisms in ischemic white matter injury. Microglia, as resident immune cells in the brain, are the main cells undergoing oxidative stress response. However, the role and molecular mechanism of oxidative stress in microglia have not been clearly elucidated during white matter ischemia.
University of Stuttgart, Institute of Biomedical Genetics, Department of Eukaryotic Genetics, Allmandring 31, 70569 Stuttgart, Germany. Electronic address:
Erythropoiesis is controlled by transcription factors that recruit epigenetic cofactors to establish and maintain erythrocyte-specific gene expression patterns while repressing alternative lineage commitment. The transcription factor TAL1 is critical for establishing erythroid gene expression. It acts as an activator or repressor of genes, depending on associated epigenetic cofactors.
Exposure to potassium dichromate (KCrO) is well known for its nephrotoxic effects on humans and animals. This study investigated the protective effects of vitamin C against KCrO-induced nephrotoxicity, focusing on its impact on altered carbohydrate metabolism, mitochondrial dysfunction, and associated molecular mechanisms in the cortical and medullary kidney segments. Male Wistar rats (n = 8) were divided into four groups: Group I received saline, Group II received a single 250 mg/kg body weight (bwt) intraperitoneal (i.
