Dissecting the Complexity of Early Heart Progenitor Cells.

Early heart development depends on the coordinated participation of heterogeneous cell sources. As pioneer work from Adriana C. Gittenberger-de Groot demonstrated, characterizing these distinct cell sources helps us to understand congenital heart defects. Despite decades of research on the segregation of lineages that form the primitive heart tube, we are far from understanding its full complexity. Currently, single-cell approaches are providing an unprecedented level of detail on cellular heterogeneity, offering new opportunities to decipher its functional role. In this review, we will focus on three key aspects of early heart morphogenesis: First, the segregation of myocardial and endocardial lineages, which yields an early lineage diversification in cardiac development; second, the signaling cues driving differentiation in these progenitor cells; and third, the transcriptional heterogeneity of cardiomyocyte progenitors of the primitive heart tube. Finally, we discuss how single-cell transcriptomics and epigenomics, together with live imaging and functional analyses, will likely transform the way we delve into the complexity of cardiac development and its links with congenital defects.Grant support PGC2018-096486-B-I00 from the Spanish Ministerio de Ciencia eInnovación and Grant H2020-MSCA-ITN-2016-722427 from the EU Horizon 2020 program to MT.MS was supported by a La Caixa Foudation PhD fellowship (LCF/BQ/DE18/11670014) and TheCompany of Biologists travelling fellowship (DEVTF181145). OH.O. is supported by the Ministerio deCiencia e Innovación (grant RTI2018-097617-J-I00). The CNIC is supported by the Spanish Ministeryof Science and the ProCNIC Foundation.S

Snail blocks the cell cycle and confers resistance to cell death

The Snail zinc-finger transcription factors trigger epithelial-mesenchymal transitions (EMTs), endowing epithelial cells with migratory and invasive properties during both embryonic development and tumor progression. During EMT, Snail provokes the loss of epithelial markers, as well as changes in cell shape and the expression of mesenchymal markers. Here, we show that in addition to inducing dramatic phenotypic alterations, Snail attenuates the cell cycle and confers resistance to cell death induced by the withdrawal of survival factors and by pro-apoptotic signals. Hence, Snail favors changes in cell shape versus cell division, indicating that with respect to oncogenesis, although a deregulation/increase in proliferation is crucial for tumor formation and growth, this may not be so for tumor malignization. Finally, the resistance to cell death conferred by Snail provides a selective advantage to embryonic cells to migrate and colonize distant territories, and to malignant cells to separate from the primary tumor, invade, and form metastasis

Cre recombinase microinjection for single-cell tracing and localised gene targeting.

Tracing and manipulating cells in embryos are essential to understand development. Lipophilic dye microinjections, viral transfection and iontophoresis have been key to map the origin of the progenitor cells that form the different organs in the post-implantation mouse embryo. These techniques require advanced manipulation skills and only iontophoresis, a demanding approach of limited efficiency, has been used for single-cell labelling. Here, we perform lineage tracing and local gene ablation using cell-permeant Cre recombinase (TAT-Cre) microinjection. First, we map the fate of undifferentiated progenitors to the different heart chambers. Then, we achieve single-cell recombination by titrating the dose of TAT-Cre, which allows clonal analysis of nascent mesoderm progenitors. Finally, injecting TAT-Cre to Mycnflox/flox embryos in the primitive heart tube revealed that Mycn plays a cell-autonomous role in maintaining cardiomyocyte proliferation. This tool will help researchers identify the cell progenitors and gene networks involved in organ development, helping to understand the origin of congenital defects.This research was supported by grant PGC2018-096486-B-I00 from the Spanish Ministerio de Ciencia e Innovación and grant H2020-MSCA-ITN-2016-722427 from the EU Horizon 2020 program to M.T. M.S. was supported by a “la Caixa” Foundation PhD fellowship (LCF/BQ/DE18/11670014) and The Company of Biologists travelling fellowship (DEVTF181145). O.H.O. is supported by the Ministerio de Ciencia e Innovación (grant RTI2018-097617-J-I00). J.N.D. received funding from grant 1380918 from the European Regional Development Fund Andalucıa 2014-2020 ́ Operating Program. Open access funding provided by Centro Nacional de Investigaciones Cardiovasculares. Deposited in PMC for immediate release.S

Angular emission properties of a layer of rare-earth based nanophosphors embedded in one-dimensional photonic crystal coatings

The angular properties of light emitted from rare-earth based nanophosphors embedded in optical resonators built in one-dimensional photonic crystal coatings are herein investigated. Strong directional dependence of the photoluminescence spectra is found. Abrupt angular variations of the enhancement caused by the photonic structure and the extraction power are observed, in good agreement with calculated polar emission patterns. Our results confirm that the optical cavity favors the extraction of different wavelengths at different angles and that integration of nanophosphors within photonic crystals provides control over the directional emission properties that could be put into practice in phosphorescent displays.Fil: Sánchez Sobrado, O.. Universidad de Sevilla. Consejo Superior de Investigaciones Cientificas. Instituto de Ciencia de Materiales de Sevilla; EspañaFil: Yacomotti, A. M.. No especifíca;Fil: Calvo, M. E.. Universidad de Sevilla. Consejo Superior de Investigaciones Cientificas. Instituto de Ciencia de Materiales de Sevilla; EspañaFil: Martinez, Oscar Eduardo. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Ocaña, M.. Universidad de Sevilla. Consejo Superior de Investigaciones Cientificas. Instituto de Ciencia de Materiales de Sevilla; EspañaFil: Núñez, N.. Universidad de Sevilla. Consejo Superior de Investigaciones Cientificas. Instituto de Ciencia de Materiales de Sevilla; EspañaFil: Levenson, J. A.. No especifíca;Fil: Míguez, H.. Universidad de Sevilla. Consejo Superior de Investigaciones Cientificas. Instituto de Ciencia de Materiales de Sevilla; Españ

Diversity of Zoanthids (Anthozoa: Hexacorallia) on Hawaiian Seamounts: Description of the Hawaiian Gold Coral and Additional Zoanthids

The Hawaiian gold coral has a history of exploitation from the deep slopes and seamounts of the Hawaiian Islands as one of the precious corals commercialised in the jewellery industry. Due to its peculiar characteristic of building a scleroproteic skeleton, this zoanthid has been referred as Gerardia sp. (a junior synonym of Savalia Nardo, 1844) but never formally described or examined by taxonomists despite its commercial interest. While collection of Hawaiian gold coral is now regulated, globally seamounts habitats are increasingly threatened by a variety of anthropogenic impacts. However, impact assessment studies and conservation measures cannot be taken without consistent knowledge of the biodiversity of such environments. Recently, multiple samples of octocoral-associated zoanthids were collected from the deep slopes of the islands and seamounts of the Hawaiian Archipelago. The molecular and morphological examination of these zoanthids revealed the presence of at least five different species including the gold coral. Among these only the gold coral appeared to create its own skeleton, two other species are simply using the octocoral as substrate, and the situation is not clear for the final two species. Phylogenetically, all these species appear related to zoanthids of the genus Savalia as well as to the octocoral-associated zoanthid Corallizoanthus tsukaharai, suggesting a common ancestor to all octocoral-associated zoanthids. The diversity of zoanthids described or observed during this study is comparable to levels of diversity found in shallow water tropical coral reefs. Such unexpected species diversity is symptomatic of the lack of biological exploration and taxonomic studies of the diversity of seamount hexacorals

Management of acute diverticulitis with pericolic free gas (ADIFAS). an international multicenter observational study

Background: There are no specific recommendations regarding the optimal management of this group of patients. The World Society of Emergency Surgery suggested a nonoperative strategy with antibiotic therapy, but this was a weak recommendation. This study aims to identify the optimal management of patients with acute diverticulitis (AD) presenting with pericolic free air with or without pericolic fluid. Methods: A multicenter, prospective, international study of patients diagnosed with AD and pericolic-free air with or without pericolic free fluid at a computed tomography (CT) scan between May 2020 and June 2021 was included. Patients were excluded if they had intra-abdominal distant free air, an abscess, generalized peritonitis, or less than a 1-year follow-up. The primary outcome was the rate of failure of nonoperative management within the index admission. Secondary outcomes included the rate of failure of nonoperative management within the first year and risk factors for failure. Results: A total of 810 patients were recruited across 69 European and South American centers; 744 patients (92%) were treated nonoperatively, and 66 (8%) underwent immediate surgery. Baseline characteristics were similar between groups. Hinchey II-IV on diagnostic imaging was the only independent risk factor for surgical intervention during index admission (odds ratios: 12.5, 95% CI: 2.4-64, P =0.003). Among patients treated nonoperatively, at index admission, 697 (94%) patients were discharged without any complications, 35 (4.7%) required emergency surgery, and 12 (1.6%) percutaneous drainage. Free pericolic fluid on CT scan was associated with a higher risk of failure of nonoperative management (odds ratios: 4.9, 95% CI: 1.2-19.9, P =0.023), with 88% of success compared to 96% without free fluid ( P <0.001). The rate of treatment failure with nonoperative management during the first year of follow-up was 16.5%. Conclusion: Patients with AD presenting with pericolic free gas can be successfully managed nonoperatively in the vast majority of cases. Patients with both free pericolic gas and free pericolic fluid on a CT scan are at a higher risk of failing nonoperative management and require closer observation

A new regulatory loop in cancer-cell invasion

2 páginas, 1 figura.Work in the laboratory is supported by grants from the Spanish Ministry of Education and Science to M.A.N. (BFU2005-05772, NAN 2004-09230-C04-04 and CON SOLI DER-ING ENIO 2010 CSD2007-00017).Peer reviewe

Mutual exclusion of transcription factors and cell behaviour in the definition of vertebrate embryonic territories

Early embryonic territories are transient entities under permanent remodelling to form newly derived cell populations that will eventually give rise to the adult tissues and organs. A vast effort has been devoted to identifying the determinants and mechanisms that define embryonic territories. Indeed, studies in the vertebrate embryo from the morula stage to the segregation of the main embryonic layers - ectoderm, mesoderm and endoderm - have highlighted the importance of the mutual exclusion/repression between pairs of transcription factors, in coordination with the control exerted over cell division, adhesion and motility. © 2012 Elsevier Ltd.Work in our labs is supported by grants from INRA (to H.A.) and from the Spanish Ministry of Science and Innovation (BFU2008-01042, CONSOLIDER-INGENIO 2010 CSD2007-00017 and CSD2007-00023) and the Generalitat Valenciana (Prometeo 2008/049) to M.A.N.Peer Reviewe

O2. The antagonism between Sox3 and Snail control cell movements to define the ectodermal/mesendodermal boundary in vertebrates

With the exception of the ectodermal derivatives (central nervous system and epidermis), adult tissues and organs are the final product of one or several rounds of epithelial to mesenchymal transitions (EMT) and the reverse process (mesenchymal to epithelial transition or MET) (Thiery et al., 2009). In the embryo itself, the first EMT event occurs at gastrulation. Cells from the single epithelial cell layer (epiblast or primitive ectoderm) move to the midline to form the primitive streak, a linear structure that bisects the embryo along the antero-posterior axis. These are the cells that undergo EMT and internalize to generate the mesoderm and the endoderm, highlighting the importance of the EMT for embryonic development, but also pointing to the need for an EMT repressor in those cells that remain in the ectoderm to become central nervous system and epidermis. Among the key evolutionary conserved factors that induce EMT at gastrulation and at additional developmental processes are the members of the Snail family (Barrallo-Gimeno and Nieto, 2009). However, they need to be downregulated in the adult, as their pathological activation leads to several prominent pathologies including tumour progression and fibrosis (Thiery et al., 2009). Therefore, it is important to identify not only those factors that induce Snail expression but also those that prevent it. These repressors are the candidates to play an important role in protecting cells from undergoing EMT to ensure the formation of ectodermal derivatives during development and to maintain epithelial homeostasis in the adult. I will present data to indicate that Sox3 and Snail factors are mutual repressors that control cells movements to define embryonic territories at gastrulation.Peer reviewe

The mutual repression between Pax2 and Snail factors regulates the epithelial/mesenchymal state during intermediate mesoderm differentiation

This article is a preprint and has not been certified by peer review.The pronephros is the first renal structure in the embryo, arising after mesenchymal to epithelial transition (MET) of the intermediate mesoderm, where Pax2 induces epithelialisation of the mesenchyme. Here we show that, in the early embryo, Snail1 directly represses Pax2 transcription maintaining the intermediate mesoderm in an undifferentiated state. Reciprocally, Pax2 directly represses Snail1 expression to induce MET upon receiving differentiation signals. We also show that BMP7 acts as one such signal by downregulating Snail1 and upregulating Pax2 expression. This, together with the Snail1/Pax2 reciprocal repression, establishes a regulatory loop in a defined region along the anteroposterior axis, the bistability domain within the transition zone, where differentiation of the neural tube and the somites are known to occur. Thus, we show that the antagonism between Snail1 and Pax2 determines the epithelial/mesenchymal state during the differentiation of the intermediate mesoderm and propose that the bistability zone extends to the intermediate mesoderm, synchronizing the differentiation of tissues aligned along the mediolateral embryonic axis.This work was supported by grants from the Spanish Ministry of Science, Innovation and Universities (MICIU RTI2018-096501-B-I00 to MAN), and the European Research Council (ERC AdG 322694) to MAN, who also acknowledges financial support from the Spanish State Research Agency, through the “Severo Ochoa Program” for Centres of Excellence in R&D (SEV-2017-0273).Peer reviewe