Lineage decision-making within normal haematopoietic and leukemic stem cells

This article belongs to the Special Issue Cellular and Molecular Mechanisms of Hematopoiesis.To produce the wide range of blood and immune cell types, haematopoietic stem cells can “choose” directly from the entire spectrum of blood cell fate-options. Affiliation to a single cell lineage can occur at the level of the haematopoietic stem cell and these cells are therefore a mixture of some pluripotent cells and many cells with lineage signatures. Even so, haematopoietic stem cells and their progeny that have chosen a particular fate can still “change their mind” and adopt a different developmental pathway. Many of the leukaemias arise in haematopoietic stem cells with the bulk of the often partially differentiated leukaemia cells belonging to just one cell type. We argue that the reason for this is that an oncogenic insult to the genome “hard wires” leukaemia stem cells, either through development or at some stage, to one cell lineage. Unlike normal haematopoietic stem cells, oncogene-transformed leukaemia stem cells and their progeny are unable to adopt an alternative pathway.This project received funding from the European Union’s Seventh Framework Programme for research, technological development and demonstration under grant agreement no 315902. Research in ISG group is partially supported by SAF2015-64420-R MINECO/FEDER,UE, RTI2018-093314-B-I00 MCIU/AEI/FEDER,UE, by Junta de Castilla y León (UIC-017, CSI001U16, and CSI234P18), by the German Carreras Foundation (DJCLS 02R-2016; DJCLS 07R/2019) and by the German Federal Office for Radiation Protection (BfS)-Germany (FKZ: 3618S32274), and by the Fundacion Unoentrecienmil (CUNINA project).Peer reviewe

Editorial: Special Issue "Stem Cell Biology and Cancer"

Cancer stem cells (CSCs) are now well-established as key players in tumor initiation, progression, and therapy resistance. Understanding the mechanisms underlying CSC generation, maintenance, and developing targeted therapies against them is crucial to improving cancer treatment outcomes. CSCs are suggested to be responsible for cancer relapse and drug resistance due to their ability to self-renew and differentiate into a heterogeneous population of cancer cells. Conventional chemotherapeutics and radiotherapy are often very effective against the bulk cells of cancer, which proliferate, but they forgive CSCs that are responsible for disease relapse. In this regard, therapeutics that specifically target CSCs may provide an effective cure for cancer.Peer reviewe

Editorial:epigenetic reprogramming and cancer development

Editorial on the Research Topic: Epigenetic Reprogramming and Cancer Development.Research in the CV-D group was partially supported by FEDER, Miguel Servet Grant (CP14/00082-AES 2013-2016) from the Instituto de Salud Carlos III (Ministerio de Economía y Competitividad), Fondo de Investigaciones Sanitarias/Instituto de Salud Carlos III (PI17/00167). Research in IS-G group was partially supported by SAF2015-64420-R MINECO/FEDER, UE, RTI2018-093314-B-I00 MCIU/AEI/FEDER, UE, by Junta de Castilla y León (UIC-017, CSI001U16, and CSI234P18), and by the German Carreras Foundation (DJCLS R13/26 and DJCLS 02R/2016). IS-G lab is a member of the EuroSyStem and the DECIDE Network funded by the European Union under the FP7 program. IS-G and CV-D have been supported by the German Federal Office for Radiation Protection (BfS) (FKZ: 3618S32274). GB lab is a member of the DECIDE Network funded by the European Union under the FP7 program.Peer reviewe

Cancer Stem Cells as a Result of a Reprogramming-Like Mechanism

Open Access: under CC BY-NCSA 3.0 license.Research in our groups is partially supported by FEDER and by MICINN (SAF2009-08803 to ISG), by Junta de Castilla y León (Proyecto Biomedicina 2009-2010 to ISG, and Proyecto Biomedicina 2010-2011 to CVD), by MEC OncoBIO Consolider-Ingenio 2010 (Ref. CSD2007- 0017) to ISG, by NIH grant (R01 CA109335-04A1) to ISG, by Sandra Ibarra Foundation to ISG, and by Group of Excellence Grant (GR15) from Junta de Castilla y Leon to ISG and JJC.Peer reviewe

The Second Oncogenic Hit Determines the Cell Fate of ETV6-RUNX1 Positive Leukemia

ETV6-RUNX1 is almost exclusively associated with childhood B-cell acute lymphoblastic leukemia (B-ALL), but the consequences of ETV6-RUNX1 expression on cell lineage decisions during B-cell leukemogenesis are completely unknown. Clinically silent ETV6-RUNX1 preleukemic clones are frequently found in neonatal cord blood, but few carriers develop B-ALL as a result of secondary genetic alterations. The understanding of the mechanisms underlying the first transforming steps could greatly advance the development of non-toxic prophylactic interventions. Using genetic lineage tracing, we examined the capacity of ETV6-RUNX1 to instruct a malignant phenotype in the hematopoietic lineage by cell-specific Cre-mediated activation of ETV6-RUNX1 from the endogenous Etv6 gene locus. Here we show that, while ETV6-RUNX1 has the propensity to trigger both T- and B-lymphoid malignancies, it is the second hit that determines tumor cell identity. To instigate leukemia, both oncogenic hits must place early in the development of hematopoietic/precursor cells, not in already committed B-cells. Depending on the nature of the second hit, the resulting B-ALLs presented distinct entities that were clearly separable based on their gene expression profiles. Our findings give a novel mechanistic insight into the early steps of ETV6-RUNX1+ B-ALL development and might have major implications for the potential development of ETV6-RUNX1+ B-ALL prevention strategies

Grade V small bowel injury after blunt abdominal trauma: a case report

Injury of the small intestine or mesentery that requires surgical intervention is relatively uncommon, presenting less than 1% of all trauma. Unstable hemodynamically patients with peritoneal irritation signs and stable hemodynamically patients with radiological signs of intestine or mesentery lesions need an exploratory laparotomy. A 33-year-old male patient, suffered a car accident in which he had a frontal impact collision and was between two structures for 30 minutes, and rescued by the fire department. Physical examination of the abdomen presents generalized pain on palpation of moderate intensity and rebound sign. An exploratory laparotomy was performed, the findings were: hemoperitoneum of 1500 ml was found, lesion in the bucket loop of 1.2 meters, 1.8 meters from the Treitz angle and 70 cm from the ileocecal valve. We managed with drainage, vascular control, resection of the devascularized intestinal loop and small bowel shotgun stoma were. The patient was transferred to the intensive care unit for hemodynamic management and a second look was performed 5 days after surgery where cavity lavage, stoma dismantling and end-to-end anastomosis of the small intestine in two planes were performed. On post-operative day 7 drains were removed, and the patient was discharged from the surgical service due to improvement, without complications. We recommend a multidisciplinary approach to patients with polytrauma, since they lead to a better and faster recovery, in the same way it allows us to detect and treat any abnormality that impacts the quality of life of patients early

PAT Ciencias: Actividades del Programa de Acción Tutorial de la Facultad de Ciencias

El principal objetivo de este proyecto es organizar una serie de actividades que puedan ser de interés general para todos los estudiantes de la Facultad de Ciencias. Estas actividades, ya sean cursos, seminarios o reuniones, tendrán diferentes objetivos: ayudar al estudiante a mejorar su organización y planificación; fomentar los programas de movilidad europea y no europea; y preparar a los estudiantes para enfrentarse a su futura vida laboral. Todas estas actividades, junto con la información que pueda ser de interés para el estudiante, serán promovidas gracias a la creación de una página de Facebook para el PAT de la Facultad de Ciencias. Con la organización de las actividades propuestas, desde el PAT de la Facultad de Ciencias se pretende favorecer el desarrollo de las competencias transversales de sus estudiantes, ayudándoles y apoyándoles para la superación de las asignaturas matriculadas. Asimismo, se pretende también fomentar la movilidad de nuestros estudiantes tanto a nivel europeo como no europeo, y prepararlos para su futura incursión en el mundo laboral

Human DNA methylomes of neurodegenerative diseases show common epigenomic patterns

Different neurodegenerative disorders often show similar lesions, such as the presence of amyloid plaques, TAU-neurotangles and synuclein inclusions. The genetically inherited forms are rare, so we wondered whether shared epigenetic aberrations, such as those affecting DNA methylation, might also exist. The studied samples were gray matter samples from the prefrontal cortex of control and neurodegenerative disease-associated cases. We performed the DNA methylation analyses of Alzheimer's disease, dementia with Lewy bodies, Parkinson's disease and Alzheimer-like neurodegenerative profile associated with Down's syndrome samples. The DNA methylation landscapes obtained show that neurodegenerative diseases share similar aberrant CpG methylation shifts targeting a defined gene set. Our findings suggest that neurodegenerative disorders might have similar pathogenetic mechanisms that subsequently evolve into different clinical entities. The identified aberrant DNA methylation changes can be used as biomarkers of the disorders and as potential new targets for the development of new therapies

Palynological investigations in the Orce Archaeological Zone, Early Pleistocene of Southern Spain

Palynological investigations in the Orce Archaeological Zone (OAZ) (Guadix-Baza Basin, Granada, Spain), Venta Micena 1 (VM1), Barranco Leon (BL) and Fuente Nueva 3 (FN3) are presented. This archaeological region is con-nected with the first Homo populations in Western Eurasia during the Early Pleistocene. The VM1 pollen record is characterized by Ephedra, and to a lesser extent, Pinus, Juniperus and evergreen Quercus, occassionally accompa-nied by Olea, Genisteae, Erica, deciduous Quercus, Alnus, Castanea, Fraxinus, Salix and Phillyrea. BL is dominated by Juniperus, Olea, Pinus, Poaceae, and evergreen Quercus. FN3 is characterized by an open Mediterranean woodland dominated by evergreen Quercus, Pinus, Juniperus and Olea, accompanied by deciduous Quercus, Castanea, Populus, Salix, Ulmus, Fraxinus, Pistacia, Phillyrea, Genisteae, Erica, Cistus, and Ephedra fragilis. Relic Tertiary taxa in OAZ include Carya, Pterocarya, Eucommia, Zelkova, and Juglans. The Early Pleistocene OAZ vegetation is a mosaic of different landscapes embracing mesophytes, thermophytes, xerophytes, xerothermophytes, and Mediterra-nean elements. These finds are compared with former pollen analyses in the region and beyond within the Ibe-rian Peninsula. (c) 2022 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/).Peer reviewe

Sporadic Creutzfeldt-Jakob disease VM1: phenotypic and molecular characterization of a novel subtype of human prion disease

The methionine (M)-valine (V) polymorphic codon 129 of the prion protein gene (PRNP) plays a central role in both susceptibility and phenotypic expression of sporadic Creutzfeldt-Jakob diseases (sCJD). Experimental transmissions of sCJD in humanized transgenic mice led to the isolation of five prion strains, named M1, M2C, M2T, V2, and V1, based on two major conformations of the pathological prion protein (PrPSc, type 1 and type 2), and the codon 129 genotype determining susceptibility and propagation efficiency. While the most frequent sCJD strains have been described in codon 129 homozygosis (MM1, MM2C, VV2) and heterozygosis (MV1, MV2K, and MV2C), the V1 strain has only been found in patients carrying VV. We identified six sCJD cases, 4 in Catalonia and 2 in Italy, carrying MV at PRNP codon 129 in combination with PrPSc type 1 and a new clinical and neuropathological profile reminiscent of the VV1 sCJD subtype rather than typical MM1/MV1. All patients had a relatively long duration (mean of 20.5 vs. 3.5 months of MM1/MV1 patients) and lacked electroencephalographic periodic sharp-wave complexes at diagnosis. Distinctive histopathological features included the spongiform change with vacuoles of larger size than those seen in sCJD MM1/MV1, the lesion profile with prominent cortical and striatal involvement, and the pattern of PrPSc deposition characterized by a dissociation between florid spongiform change and mild synaptic deposits associated with coarse, patch-like deposits in the cerebellar molecular layer. Western blot analysis of brain homogenates revealed a PrPSc type 1 profile with physicochemical properties reminiscent of the type 1 protein linked to the VV1 sCJD subtype. In summary, we have identified a new subtype of sCJD with distinctive clinicopathological features significantly overlapping with those of the VV1 subtype, possibly representing the missing evidence of V1 sCJD strain propagation in the 129MV host genotype