Luis del Peso

Autonomous University of Madrid | UAM · Department Biochemistry

Knowledge of the molecular mechanisms that underlie the regulation of major adaptive responses to an unbalanced oxygen tension is central to understanding tissue homeostasis and disease. Hypoxia-inducible transcription factors (HIFs) coordinate changes in the transcriptome that control these adaptive responses. Here, we focused on the functional ro...

Single-cell transcriptomics techniques, such as scRNA-seq, attempt to characterize gene expression profiles in each cell of a heterogeneous sample individually. Due to growing amounts of data generated and the increasing complexity of the computational protocols needed to process the resulting datasets, the demand for dedicated training in mathemat...

Knowledge of the molecular mechanisms that underlie the regulation of the major adaptive responses to an unbalanced oxygen tension is central to understanding tissue homeostasis and disease. Hypoxia-inducible transcription factors (HIFs) coordinate changes in the transcriptome that control these adaptive responses. Here, we focused on the functiona...

Background: Differentiation of mouse stem cells (mESC) to embryonic bodies (EBs) is a widely used approach to model early stages of development. In this study, we employed single-cell transcriptomics to examine the effect of hypoxia on the differentiation of different cell populations in EBs. Results: We differentiated EBs for 8 or 10 days, with t...

Single-cell transcriptomics techniques, such as scRNA-seq, attempt to characterize gene expression profiles in each cell of a heterogeneous sample individually. Due to growing amounts of data generated and the increasing complexity of the computational protocols needed to process the resulting datasets, the demand for dedicated training in mathemat...

Preservation of blood vessel integrity, which is critical for normal physiology and organ function, is controlled at multiple levels, including endothelial junctions. However, the mechanism that controls the adequate assembly of endothelial cell junctions is not fully defined. Here, we uncover TAp73 transcription factor as a vascular architect that...

Integrating transcriptional profiles results in identifying gene expression signatures that are more robust than those obtained for individual datasets. However, a direct comparison of datasets derived from heterogeneous experimental conditions is problematic, hence their integration requires applying of specific meta-analysis techniques. The trans...

Sarcomas are a heterogeneous group of tumors in which the role of ERK5 is poorly studied. To clarify the role of this MAPK in sarcomatous pathology, we used a murine 3-methyl-cholanthrene (3MC)-induced sarcoma model. Our data show that 3MC induces pleomorphic sarcomas with muscle differentiation, showing an increased expression of ERK5. Indeed, thi...

Molecular gene signatures are useful tools to characterize the physiological state of cell populations, but most have developed under a narrow range of conditions and cell types and are often restricted to a set of gene identities. Focusing on the transcriptional response to hypoxia, we aimed to generate widely applicable classifiers sourced from t...

Vascular development comprises vasculogenesis, sprouting and non-sprouting angiogenesis and vessel assembly and remodeling. These processes require the coordinated regulation of intercellular junctions to maintain vascular architecture and vessel barrier. Here we demonstrate a key function for p73 transcription factor orchestrating transcriptional...

Molecular gene signatures are useful tools to characterize the physiological state of cell populations, but most have developed under a narrow range of conditions and cell types and are often restricted to a set of gene identities. Focusing on the transcriptional response to hypoxia, we aimed to generate widely applicable classifiers sourced from t...

Molecular gene signatures are useful tools to characterize the physiological state of cell populations, but most have developed under a narrow range of conditions and cell types and are often restricted to a set of gene identities. Focusing on the transcriptional response to hypoxia, we aimed to generate widely applicable classifiers sourced from t...

Background Integrating transcriptional profiles results in the identification of gene expression signatures that are more robust than those obtained for individual datasets. However, direct comparison of datasets derived from heterogeneous experimental conditions is not possible and their integration requires the application of specific meta-analys...

Colon and rectal tumors, often referred to as colorectal cancer, show different gene expression patterns in studies that analyze whole tissue biopsies containing a mix of tumor and non-tumor cells. To better characterize colon and rectal tumors, we investigated the gene expression profile of organoids generated from endoscopic biopsies of rectal tu...

Cells adapt to environmental changes, including fluctuations in oxygen levels, through the induction of specific gene expression programs. However, most transcriptomic studies do not distinguish the relative contribution of transcription, RNA processing and RNA degradation processes to cellular homeostasis. Here we used metabolic labeling followed...

Angiogenesis, the main mechanism that allows vascular expansion for tissue regeneration or disease progression, is often triggered by an imbalance between oxygen consumption and demand. Here, by analyzing changes in the transcriptomic profile of endothelial cells (ECs) under hypoxia we uncovered that the repression of cell cycle entry and DNA repli...

Intestine is a major target of vitamin D and several studies indicate an association between vitamin D deficiency and inflammatory bowel diseases (IBD), but also increased colorectal cancer (CRC) risk and mortality. However, the putative effects of 1α,25‐dihydroxyvitamin D3 (calcitriol), the active vitamin D metabolite, on human colonic stem cells...

The computational identification of the transcription factors (more generally, transcription regulators, TR) responsible for the co-regulation of a specific set of genes is a common problem found in genomic analysis. Herein, we describe TFEA.ChIP, a tool that makes use of ChIP-seq datasets to estimate and visualize TR enrichment in gene lists repre...

Cells adapt to environmental changes, including fluctuations in oxygen levels, through the induction of specific gene expression programs. However, most transcriptomic studies do not distinguish the relative contribution of transcription, RNA processing and RNA degradation processes to cellular homeostasis. Here we used metabolic labeling followed...

The Wnt/β-catenin signalling pathway is essential for intestinal epithelium homeostasis, but its aberrant activation is a hallmark of colorectal cancer (CRC). Several studies indicate that the bioactive vitamin D metabolite 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) inhibits proliferation and promotes epithelial differentiation of colon carcinoma cell...

Objective— Pathological neovascularization is crucial for progression and morbidity of serious diseases such as cancer, diabetic retinopathy, and age-related macular degeneration. While mechanisms of ongoing pathological neovascularization have been extensively studied, the initiating pathological vascular remodeling (PVR) events, which precede neo...

Hypoxia or reduced oxygen availability has been studied extensively for its ability to activate specific genes. Hypoxia-induced gene expression is mediated by the HIF transcription factors, but not exclusively so. Despite the extensive knowledge about how hypoxia activates genes, much less is known about how hypoxia promotes gene repression. In thi...

The identification of transcription factors (TFs) responsible for the co-regulation of specific sets of genes is a common problem in transcriptomics. Herein we describe TFEA.ChIP, a tool to estimate and visualize TF enrichment in gene lists representing transcriptional profiles. To generate the gene sets representing TF targets, we gathered ChIP-Se...

Hypoxia, or reduced oxygen availability, has been studied extensively for its ability to activate specific genes. Hypoxia induced gene expression is mediated by the HIF transcription factors, although not exclusively so. Despite the great knowledge on the mechanisms by which hypoxia activates genes, much less is known about how hypoxia promotes gen...

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Cells adapt to environmental changes, including fluctuations in oxygen levels, through the induction of specific gene expression programs. To identify genes regulated by hypoxia at the transcriptional level, we pulse-labeled HUVEC cells with 4-thiouridine and sequenced nascent transcripts. Then, we searched genome-wide binding profiles from the ENC...

Colorectal cancer results from the malignant transformation of colonic epithelial cells. Stromal fibroblasts are the main component of the tumour microenvironment, and play an important role in the progression of this and other neoplasias. Wnt/β-catenin signalling is essential for colon homeostasis, but aberrant, constitutive activation of this pat...

Cells adapt to environmental changes, including fluctuations in oxygen levels, through the induction of specific gene expression programs. To identify genes regulated by hypoxia at the transcriptional level, we pulse-labeled HUVEC cells with 4-thiouridine and sequenced nascent transcripts. Then, we searched genome-wide binding profiles from the ENC...

Rationale: Global Lung Function Initiative recommends reporting lung function measures as z-score, and a classification of airflow limitation (AL) based on this parameter has recently been proposed. Objective: To evaluate the prognostic capacity of the AL classifications based on z-score or percentage predicted in patients with chronic obstructi...

A wide range of diseases course with an unbalance between the consumption of oxygen by tissues and its supply. This situation triggers a transcriptional response, mediated by the hypoxia inducible factors (HIFs), that aims to restore oxygen homeostasis. Little is known about the inter-individual variation in this response and its role in the progre...

Abstract The hypoxic areas of solid cancers represent a negative prognostic factor irrespective of which treatment modality is chosen for the patient. Still, after almost 80 years of focus on the problems created by hypoxia in solid tumours, we still largely lack methods to deal efficiently with these treatment-resistant cells. The consequences of...

The presence of hypoxic regions in solid tumors is an adverse prognostic factor for patient outcome. Here, we show that hypoxia induces the expression of Ephrin-A3 through a novel hypoxia-inducible factor (HIF)-mediated mechanism. In response to hypoxia, the coding EFNA3 mRNA levels remained relatively stable, but HIFs drove the expression of previ...

Chromatin immunoprecipitation (ChIP) coupled to high-throughput sequencing (ChIP-Seq) techniques can reveal DNA regions bound by transcription factors (TF). Analysis of the ChIP-Seq regions is now a central component in gene regulation studies. The need remains strong for methods to improve the interpretation of ChIP-Seq data and the study of speci...

Pigment epithelium-derived factor (PEDF), a member of the serine protease inhibitor superfamily, has potent anti-metastatic effects in cutaneous melanoma through its direct actions on endothelial and melanoma cells. Here we show that PEDF expression positively correlates with microphthalmia-associated transcription factor (MITF) in melanoma cell li...

Extracellular signal-regulated kinase 5 (ERK5), also known as big mitogen-activated protein kinase (MAPK) 1, is implicated in a wide range of biologic processes, which include proliferation or vascularization. Here, we show that ERK5 is degraded through the ubiquitin-proteasome system, in a process mediated by the tumor suppressor von Hippel-Lindau...

This article describes the transition from a traditional instructor-centered course, based on lectures, to a student-centered course based on active learning methodologies as part of the reform of the Spanish higher education system within the European Higher Education Area (EHEA). Specifically, we describe the use of active learning methodologies...

Hypoxia-inducible factors (HIFs) mediate the transcriptional adaptation of hypoxic cells. The extensive transcriptional programm regulated by HIFs involves the induction of genes controlling angiogenesis, cellular metabolism, cell growth, metastasis, apoptosis, extracellular matrix remodeling and others. HIF is a heterodimer of HIF-α and HIF-β subu...

The transcriptional response driven by Hypoxia-inducible factor (HIF) is central to the adaptation to oxygen restriction. Despite recent characterization of genome-wide HIF DNA binding locations and hypoxia-regulated transcripts in different cell types, the molecular bases of HIF target selection remain unresolved. Herein, we combined multi-level e...

HRE, AP1, CREB, CEBPB binding sites and control mutations introduced in LDHA, CA9 and GYS1 promoter constructs. (XLSX)

Correlation between normoxic basal expression and hypoxia inducibility (known HIF targets). (XLSX)

Enriched gene annotation clusters in core HIF binding regions. (XLSX)

Enriched gene annotation terms in transcription factors associated to sequence motifs overrepresented in core HIF binding regions. (XLSX)

Construction of a background set of control sequences resembling core HIF binding regions. (PDF)

Candidate HIF1alpha-binding regions identified by ChIP-chip analysis in HeLa cells. (XLSX)

Distribution of conserved HBSs in ChIP-chip results across different cell types. (XLSX)

Integrated set of core HIF binding regions. (XLSX)

Ischemia/reperfusion (I/R) is at the basis of renal transplantation and acute kidney injury. Molecular mechanisms underlying proximal tubule response to I/R will allow the identification of new therapeutic targets for both clinical settings. microRNAs have emerged as crucial and tight regulators of the cellular response to insults including hypoxia...

Scheme of in vitro H/R and transfection protocols. (A) Schematic representation of H/R protocol where changes in nutrients and oxygen tension are indicated for each condition, represented in different arrows. DMEM medium is used for NRK-52E cells, whereas DMEM-F12 is employed for HK-2 cell culture. HBSS is a minimum medium with balanced salt concen...

Schematic representation of vectors used in reporter assays experiments. (A) Scheme of luciferase-KIF3B 3′UTR vectors S1A and S3B. Two independent KIF3B-3′UTR vectors, named as S1A and S3B were. (B) Empty vector (PGL3 control) used as control in luciferase reporter experiments. (C) Renilla luciferase vector used for normalization. (TIF)

Ischemia/Reperfusion in rats produces renal dysfunction and proximal tubules damage. (A) Renal function studies in rats submitted to I/R protocol. Serum creatinine and urea were measured for renal function studies. Data are presented as mean±s.e.m. of five animals per condition and asterisks indicate statistical significance compared to Sham condit...

Here we present the Transcription Factor Encyclopedia (TFe), a new web-based compendium of mini review articles on transcription factors (TFs) that is founded on the principles of open access and collaboration. Our consortium of over 100 researchers has collectively contributed over 130 mini review articles on pertinent human, mouse and rat TFs. No...

Classification of transcription factors in TFe. There are 803 human, mouse, and rat articles in TFe, most of which are organized into groups, families and subfamilies of TFs. The classification scheme utilized in TFe is derived from the work of Fulton et al. [5] in TFCat. There are 8 large groups, which are further subclassified into 34 families. S...

PDF of released article. The PDF version of the human FOXL2 article. Other PDF versions of released TFe articles can be accessed on the TFe website.

Relationship Between Pfam domains and PDB records. A list of Pfam binding domains followed by PDB records in which the domains can be found.

Data of released articles. Additional data related to the released mini review articles to supplement the four-page PDF versions, arranged in alphabetical order by TF name.

The TFe article structure. Articles in TFe are organized into ten tabs labeled 'Summary', 'Structure', 'TFBS', 'Targets', 'Protein', 'Interactions', 'Genetics', 'Expression', 'Ontologies', and 'Papers'. Each tab, with the exception of the Ontologies and Papers tabs, typically begins with a brief overview written by the authors, followed by a mixtur...