A5032584662- Acute Myeloid Leukemia Research
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Cancer Genomics and Diagnostics
- Single-cell and spatial transcriptomics
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Epigenetics and DNA Methylation
- Hematopoietic Stem Cell Transplantation
- Dermatology and Skin Diseases
- Retinoids in leukemia and cellular processes
- RNA Research and Splicing
- Nuclear Structure and Function
- Acute Lymphoblastic Leukemia research
- Health, Environment, Cognitive Aging
- Genetics and Neurodevelopmental Disorders
- Zebrafish Biomedical Research Applications
- RNA modifications and cancer
- Cancer-related molecular mechanisms research
- Skin Protection and Aging
- Skin and Cellular Biology Research
- Breast Cancer Treatment Studies
Josep Carreras Leukaemia Research Institute
2022-2025
Abstract Skin aging is characterized by structural and functional changes that contribute to age-associated frailty. This probably depends on synergy between alterations in the local niche stem cell-intrinsic changes, underscored proinflammatory microenvironments drive pleotropic changes. The nature of these inflammatory cues, or how they affect tissue aging, unknown. Based single-cell RNA sequencing dermal compartment mouse skin, we show a skew towards an IL-17-expressing phenotype T helper...
Abstract Recent findings suggest that Hematopoietic Stem Cells (HSC) and progenitors arise simultaneously independently of each other already in the embryonic aorta-gonad mesonephros region, but it is still unknown how their different features are established. Here, we uncover IκBα ( Nfkbia , inhibitor NF-κB) as a critical regulator HSC proliferation throughout development. balances retinoic acid signaling levels together with epigenetic silencer, PRC2, specifically HSCs. Loss decreases...
Abstract Alterations in epigenetic marks, such as DNA methylation, represent a hallmark of cancer that has been successfully exploited for therapy myeloid malignancies. Hypomethylating agents (HMA), azacitidine, have become standard-of-care to treat myelodysplastic syndromes (MDS), neoplasms can evolve into acute leukemia. However, our capacity identify who will respond HMAs, and the duration response, remains limited. To shed light on this question, we leveraged unprecedented analytic power...
Rett syndrome (RTT) is a severe neurodevelopmental disorder primarily caused by loss-of-function mutations in the MECP2 gene, resulting diverse cellular dysfunctions. Here, we investigated role of long noncoding RNA (lncRNA) NEAT1 context MeCP2 deficiency using human neural cells and RTT patient samples. Through single-cell sequencing molecular analyses, found that markedly downregulated knockout (KO) at various stages differentiation. downregulation correlated with aberrant activation mTOR...
The indexed individual, from now on termed M116, was the world's oldest verified living person January 17th 2023 until her passing August 19th 2024, reaching age of 117 years and 168 days (https://www.supercentenarian.com/records.html). She a Caucasian woman born March 4th 1907 in San Francisco, USA, Spanish parents settled Spain since she 8. Although centenarians are becoming more common demographics human populations, so-called supercentenarians (over 110 old) still rarity. In Catalonia,...
Summary Recent findings are challenging the classical hematopoietic model in which long-term stem cells (LT-HSC) base of system. Clonal dynamics analysis system indicate that LT-HSC not main contributors normal hemapoiesis physiological conditions and is mainly maintained by multipotent progenitors (MPPs, hereafter HPC) LT-HSCs mostly a non-active state. The first HSCs emerge from aorta-gonad mesonephros (AGM) region along with (HPC) within clusters. Molecular pathways determine HSC fate...
<p>Clonal landscape of MDS patients</p>
<p>Impact of AZA treatment on mutant cell populations in patients with hematological improvement (HI)</p>
<div>Abstract<p>Alterations in epigenetic marks, such as DNA methylation, represent a hallmark of cancer that has been successfully exploited for therapy myeloid malignancies. Hypomethylating agents (HMA), azacitidine, have become standard-of-care to treat myelodysplastic syndromes (MDS), neoplasms can evolve into acute leukemia. However, our capacity identify who will respond HMAs, and the duration response, remains limited. To shed light on this question, we leveraged...
<p>Karyotype and mutations (bulk NGS single-cell DNAseq) at diagnosis for the studied MDS cases</p>
<p>Clonal evolution of responder and nonresponder patients with MDS upon AZA treatment. <b>A,</b> Clonal phylogenies #3 #14 (responders) #4 #8 (nonresponders) at diagnosis. Dot size represents clone size. <b>B,</b> Fishplots (nonresponders), illustrating the clonal distribution diagnosis after <b>C,</b> Proportion mutant cells (left) predominant (right) in Dx, diagnosis; Aza, treatment.</p>
<p>Distribution of mutant cells within the BM compartments defined by immunophenotype. <b>A,</b> Percentage progenitor, immature erythroid and myeloid (Pro_Ery_Mye) compared with lymphoid in each patient at diagnosis (top); percentage (bottom, left); or T, B, NK right) diagnosis. <b>B,</b> UMAP from all samples colored number mutations per cell (left); type proportions according to (right). <b>C,</b> gene mutational status. WT, wild-type; MUT,...
<p>Effect of AZA treatment on wild-type cell populations in responder patients</p>
<p>Distribution of mutations in CHIP-associated genes at diagnosis according to response status</p>
<p>Karyotype and mutations (bulk NGS single-cell DNAseq) at diagnosis for the studied MDS cases</p>
<p>Antibodies used for single cell surface protein sequencing</p>
<p>Amplicon coverage for the custom single cell DNA sequencing panel</p>
<p>Mutational landscape of patients with the studied MDS. <b>A,</b> Summary study workflow. <b>B,</b> Oncoprint indicating mutations present in patient cohort, at diagnosis and after AZA treatment, colored by coding impact. Multi-hit means presence more than one mutation same impact (missense, nonsense, or frameshift) gene. <b>C,</b> UpSet plot illustrating exclusive intersection mutated pathways The are according to response status (green,...
<p>Mutational landscape of patients with the studied MDS. <b>A,</b> Summary study workflow. <b>B,</b> Oncoprint indicating mutations present in patient cohort, at diagnosis and after AZA treatment, colored by coding impact. Multi-hit means presence more than one mutation same impact (missense, nonsense, or frameshift) gene. <b>C,</b> UpSet plot illustrating exclusive intersection mutated pathways The are according to response status (green,...
<p>Clinicopathologic information of the studied MDS patients</p>
<p>Fisher exact test for each mutated pathway, comparing responders vs. non-responders at diagnosis</p>
<p>Characterization of BM cell populations patients with MDS based on scProt-seq data. <b>A,</b> UMAP cells from all samples colored by abundance the depicted proteins. <b>B,</b> type annotation. <b>C,</b> Cell proportions at diagnosis and after AZA treatment in responders. *, scCODA FDR <0.1. <b>D,</b> UMAPs for responder patients. Dx, diagnosis; Aza, treatment.</p>
<p>Clonal evolution of responder and nonresponder patients with MDS upon AZA treatment. <b>A,</b> Clonal phylogenies #3 #14 (responders) #4 #8 (nonresponders) at diagnosis. Dot size represents clone size. <b>B,</b> Fishplots (nonresponders), illustrating the clonal distribution diagnosis after <b>C,</b> Proportion mutant cells (left) predominant (right) in Dx, diagnosis; Aza, treatment.</p>
<p>Clonal landscape of the progenitor, immature erythroid, myeloid and lymphoid compartments at diagnosis for each patient</p>