A5088585621- Erythrocyte Function and Pathophysiology
- Hemoglobinopathies and Related Disorders
- Acute Myeloid Leukemia Research
- Single-cell and spatial transcriptomics
- CRISPR and Genetic Engineering
- Epigenetics and DNA Methylation
- Immune cells in cancer
- T-cell and B-cell Immunology
- Genomics and Chromatin Dynamics
- Blood groups and transfusion
- Blood disorders and treatments
- Prenatal Screening and Diagnostics
- Heme Oxygenase-1 and Carbon Monoxide
- RNA modifications and cancer
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Gene Regulatory Network Analysis
- Chronic Myeloid Leukemia Treatments
- Hematopoietic Stem Cell Transplantation
- Immune responses and vaccinations
- Retinoids in leukemia and cellular processes
- Immune Cell Function and Interaction
- Cannabis and Cannabinoid Research
- Lymphoma Diagnosis and Treatment
University of Milano-Bicocca
2006-2020
University College London
2012-2015
University of Oxford
2008-2013
MRC Weatherall Institute of Molecular Medicine
2008-2013
London Cancer
2013
John Radcliffe Hospital
2008-2011
Medical Research Council
2008
We used the paradigmatic GATA-PU.1 axis to explore, at systems level, dynamic relationships between transcription factor (TF) binding and global gene expression programs as multipotent cells differentiate. combined ChIP-seq of GATA1, GATA2, PU.1 with profiling during differentiation erythroid neutrophil lineages. Our analysis reveals (1) differential complexity sequence motifs bound by PU.1; (2) scope interplay GATA1 GATA2 within, transitions between, different cell compartments, extent...
d We present a method for inferring gene regulatory networks (GRNs) from single cells Lineage cross-antagonism is key property of GRNs early lineage commitment Ddit3 node in erythroid programming A Ddit3-Gata2 axis antagonizes myeloid and enables programs
Prospective isolation is critical for understanding the cellular and molecular aspects of stem cell heterogeneity. Here, we identify surface antigen CD9 as a positive marker that provides simple alternative hematopoietic at high purity. Crucially, affords capture all cells in murine bone marrow absence contaminating populations lack authentic function. Using tool to subdivide stem-cell-containing populations, provide evidence heterogeneity cellular, functional, levels.
We observed that binding sites for the ubiquitously expressed transcription factor CP2 were present in regulatory regions of multiple erythroid genes. In these regions, site was adjacent to a GATA-1. Using three such (from genes encoding factors GATA-1, EKLF, and p45 NF-E2), we demonstrated functional importance CP2/GATA-1 sites. particular, binds GATA-1 HS2 enhancer, generating ternary complex with DNA. Mutations consensus greatly impaired activity transient transfection assays K562 cells....
Abstract SOX6 is a HMG-box transcription factor expressed in wide range of tissues. Recent data show that expression altered different cancers, the majority cases being downregulated. To date, no are available about role hematological malignancies. Here we demonstrate overexpressing BCR-ABL1 + B-ALL cells unable to promote leukemia mouse model. Starting from this observation, extended our study panel human leukemic carrying genetic lesions distinctive types leukemias and myeloproliferative...
Abstract The Sox6 transcription factor is crucial for terminal maturation of definitive red blood cells. Sox6-null mouse fetuses present misshapen and nucleated erythrocytes, due to impaired actin assembly cytoskeleton stability. These defects are accompanied with a reduced survival −/− cells, resulting in compensated anemia. Sox6-overexpression K562 cells human primary ex vivo erythroid cultures enhances differentiation leads hemoglobinization, the hallmark maturation. To obtain an overview...
The human fetal γ-globin gene is repressed in the adult stage through complex regulatory mechanisms involving transcription factors and epigenetic modifiers. Reversing repression, or maintaining its expression by manipulating mechanisms, has become a major clinical goal treatment of β-hemoglobinopathies. Here, we identify orphan nuclear receptor Coup-TFII (NR2F2/ARP-1) as an embryonic/fetal activator expression. We show that expressed early erythropoiesis yolk sac origin, together with...
The identification of drugs capable reactivating γ-globin to ameliorate β-thalassemia and Sickle Cell anemia is still a challenge, as available inducers have limited clinical indications. High-throughput screenings (HTS) aimed identify new potentially therapeutic require suitable first-step-screening methods combining the possibility detect variation in γ/β globin ratio with robustness cell line. We took advantage K562 line variant expressing β-globin (β-K562) set up multiplexed high-content...
Erythroid-Myeloid-Lymphoid cells (EML) are a multipotent haematopoietic cell line of mouse bone marrow origin capable long-term maintenance in vitro the presence SCF (stem factor) (Tsai et al., 1994). The self-renewal capacity EML is conferred by dominant-negative retinoic acid receptor (RAR) originally delivered retroviral transduction 1994), which arrests at an early progenitor stage blocked from normal progression into myeloid differentiation. RAR trans-gene does not interfere with...