A5018532888- Hemoglobinopathies and Related Disorders
- Erythrocyte Function and Pathophysiology
- Iron Metabolism and Disorders
- RNA modifications and cancer
- Pluripotent Stem Cells Research
- Genomics and Chromatin Dynamics
- Epigenetics and DNA Methylation
- RNA and protein synthesis mechanisms
- MicroRNA in disease regulation
- Congenital heart defects research
- DNA and Nucleic Acid Chemistry
- Blood groups and transfusion
- RNA Research and Splicing
- Prenatal Screening and Diagnostics
- Cancer Cells and Metastasis
- CRISPR and Genetic Engineering
- Neurogenesis and neuroplasticity mechanisms
- Tissue Engineering and Regenerative Medicine
- Cancer-related molecular mechanisms research
- Renal and related cancers
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Blood disorders and treatments
- Erythropoietin and Anemia Treatment
- Acute Myeloid Leukemia Research
- T-cell and Retrovirus Studies
University of Milano-Bicocca
2012-2025
European Institute of Oncology
2003-2014
IFOM
2014
University of Milan
1995-2013
Harvard University
2009-2012
Brigham and Women's Hospital
2011-2012
University of Modena and Reggio Emilia
2012
Montefiore Medical Center
2011
Beth Israel Deaconess Medical Center
2011
Albert Einstein College of Medicine
2011
In many species, the Sox2 transcription factor is a marker of nervous system from beginning its development, and we have previously shown that expressed in embryonic neural stem cells. It also in, essential for, totipotent inner cell mass cells other multipotent lineages, ablation causes early lethality. To investigate role system, generated different mouse mutant alleles: null allele(Sox2β-geo `knock-in'), regulatory allele (Sox2ΔENH), which cell-specific enhancer deleted. precursors...
ABSTRACT Sox2 is one of the earliest known transcription factors expressed in developing neural tube. Although it throughout early neuroepithelium, we show that its later expression must depend on activity more than regionally restricted enhancer element. Thus, by using transgenic assays and homologous recombination-mediated deletion, identify a region upstream (−5.7 to −3.3 kb) which can not only drive β-geo transgene dorsal telencephalon, but required do so context endogenous gene. The...
We investigated the mechanism whereby expression of a transgene encoding locally acting isoform insulin-like growth factor 1 (mIGF-1) enhances repair skeletal muscle damage. Increased recruitment proliferating bone marrow cells to injured MLC / mIgf-1 transgenic muscles was accompanied by elevated stem cell production in response distal trauma. Regenerating contained increased populations expressing markers, exhibited accelerated myogenic differentiation, expressed markers regeneration and...
Male mice lacking expression of Plzf, a DNA sequence-specific transcriptional repressor, show progressive germ cell depletion due to exhaustion the spermatogonial stem population. This is likely deregulated genes controlling switch between self-renewal and differentiation. Here we that Plzf directly represses transcription kit, hallmark both endogenous kit reporter gene under control promoter region. A discrete sequence promoter, required for Plzf-mediated repression, bound by in vivo vitro....
The transcription factor Sox2 is active in neural stem cells, and Sox2`knockdown' mice show defects stem/progenitor cells the hippocampus eye, possibly some neurons. In humans, heterozygous deficiency associated with eye abnormalities, hippocampal malformation epilepsy. To better understand role of Sox2, we performed vitro differentiation studies on cultured from embryonic adult brains `knockdown' mutants. expression high undifferentiated declines differentiation, but remains visible at...
The stem cell-determining transcription factor Sox2 is required for the maintenance of normal neural cells. In this study, we investigated requirement in cancer stem-like cells using a conditional genetic deletion mutant mouse model platelet-derived growth factor-induced malignant oligodendroglioma. Transplanting wild-type oligodendroglioma into brain generated lethal tumors, but mice transplanted with Sox2-deleted remained free tumors. Loss tumor-initiating ability was reversed by...
The SOX2 transcription factor is critical for neural stem cell (NSC) maintenance and brain development. Through chromatin immunoprecipitation (ChIP) interaction analysis (ChIA-PET), we determined genome-wide SOX2-bound regions Pol II-mediated long-range interactions in brain-derived NSCs. DNA was highly enriched distal interacting with promoters carrying epigenetic enhancer marks. Sox2 deletion caused widespread reduction of decreased gene expression. Genes showing reduced expression...
The Sox2 transcription factor is expressed early in the stem cells of blastocyst inner cell mass and, later, neural cells. We previously identified a 5'-regulatory region directing transgene expression to and precursors forebrain. Here, we identify core enhancer element able specify forebrain mouse embryos, show that same efficiently activates mass-derived embryonic (ES) Mutation POU binding sites, recognize factors Brn1 Brn2, shows these sites contribute activity are also essential for ES...
Cells expressing the herpes simplex-thymidine kinase (HS-TK) gene as a consequence of retroviral transduction, well TK-negative (TK¯) bystander cells, can be killed by treatment with ganciclovir (GCV). In vitro, this "bystander effect," has been attributed to metabolic cooperation through gap junctions or uptake apoptotic vesicles. We show that GCV kills U-87 glioma cells cocultured express TK (TK+) but have lost capacity for releasing particles. A photometric enzyme immunoassay identifies...
Cumulative evidence indicates that myocardium responds to growth or injury by recruitment of stem and/or progenitor cells participate in repair and regenerative processes. Unequivocal identification this population has been hampered lack reagents markers specific the recruited population, leading controversies regarding nature these cells. Use a transgenic mouse expressing green fluorescent protein driven c-kit promoter allows for unambiguous cell population. Green (GFP) labels fraction...
Embryonic and fetal myocardial growth is characterized by a dramatic increase in myocyte number, but whether the expansion of compartment dictated activation commitment resident cardiac stem cells (CSCs), division immature myocytes or both currently unknown.In this study, we tested prenatal development controlled differentiation CSCs c-kit-positive mouse heart triggered spontaneous Ca(2+) oscillations.We report that embryonic-fetal are self-renewing, clonogenic multipotent vitro vivo. The...
How Kit expression is regulated in the germline still an open question. SOHLH1 and SOHLH2, two bHLH transcription factors specifically expressed germ cells, have been recently involved differentiation of spermatogonia oocytes. In male, deletion each factor leads to disappearance Kit-expressing prepuberal testis. female, both SOHLH2 ablations are responsible oocyte loss neonatal ovary. To investigate if might be by these male we first performed study during fetal postnatal development....
Abstract The Sox2 transcription factor is necessary for the long-term self-renewal of neural stem cells (NSCs). Its mechanism action still poorly defined. To identify molecules regulated by Sox2, and acting in mouse NSC maintenance, we transduced, into Sox2-deleted NSC, genes whose expression strongly downregulated following loss (Fos, Jun, Egr2), individually or combination. Fos alone rescued proliferation, as shown vitro cell growth clonal analysis. Furthermore, pharmacological inhibition...
We applied cDNA selection methods to a genomic clone (YAC 761B5) from chromosome 21 located in the so‐called ‘Down critical region’ 21q22.3. Starting human fetal heart and brain mRNAs we obtained sequenced several clones. One of these clones (Down region aspartic protease (DRAP), named also BACE2 according gene nomenclature) revealed striking nucleotide amino acid sequence identity with motifs present members family. In particular sequences comprising two catalytic sites found all mammalian...
ABSTRACI'We investigated the effects of antiviral agent distamycin A and a derivative (FCE 24517) which possesses antineoplastic activity on binding some regulatory proteins to DNA.Both compounds inhibited DNA ubiquitous octamer factor OTF 1 erythroid specific GATAAG protein ( NFE 1).This was shown using electrophoretic mobility shift assay fragment human y-globin gene promoter (-156 -201), same with point mutation (T C mutation) known have an increased affinity for 1, histone H2B mouse al...
The hematological phenotypes of several Mediterranean patients with delta beta-thalassemia and hereditary persistence fetal hemoglobin have been characterized. Although clinical characteristics are essentially superimposable in all heterozygous beta-thalassemics, these show typical G gamma/A gamma ratios their Hb F, ranging from approximately 0.07 Sardinian to 0.15 Sicilian 0.35 Spanish patients. A Sardinian-(isoleucine-75 leads threonine) is found accounts for the production heterozygotes,...
Journal Article The effects of HPFH mutations in the human γ-globin promoter on binding ubiquitous and erythroid specific nuclear factors Get access R. Mantovani, Mantovani Dipartimento di Genetica e Biologia dei Microrganismi, Università Milano Studio MilanMilan, Italy Search for other works by this author on: Oxford Academic PubMed Google Scholar N. Malgaretti, Malgaretti S. Nicolis, Nicolis A. Ronchi, Ronchi B. Giglioni, Giglioni 1Centro per lo della Patologia Cellulare del CNRMilan,...