Uncovering the Number and Clonal Dynamics of Mesp1 Progenitors during Heart Morphogenesis.

The heart arises from distinct sources of cardiac progenitors that independently express Mesp1 during gastrulation. The precise number of Mesp1 progenitors that are specified during the early stage of gastrulation, and their clonal behavior during heart morphogenesis, is currently unknown. Here, we used clonal and mosaic tracing of Mesp1-expressing cells combined with quantitative biophysical analysis of the clonal data to define the number of cardiac progenitors and their mode of growth during heart development. Our data indicate that the myocardial layer of the heart derive from ∼250 Mesp1-expressing cardiac progenitors born during gastrulation. Despite arising at different time points and contributing to different heart regions, the temporally distinct cardiac progenitors present very similar clonal dynamics. These results provide insights into the number of cardiac progenitors and their mode of growth and open up avenues to decipher the clonal dynamics of progenitors in other organs and tissues.S.C. and N.M. are supported by fellowship of the FRS/FRIA. F.L has been supported by the EMBO longterm fellowship. B.D.S. and S.R. are supported by Wellcome Trust (grant number 098357/Z/12/Z). C.B. is an investigator of WELBIO. This work was supported by the FNRS, the ULB foundation, the European Research Council (ERC), and the foundation Bettencourt Schueller (C.B. and F.L.).This is the final version of the article. It first appeared from Elsevier/Cell Press via http://dx.doi.org/10.1016/j.celrep.2015.12.01

El Estado colombiano ante el emprendimiento en clave de género

La formulación de políticas públicas diferenciadas tiene como base no sólo las demandas internacionales a las que se ha acogido el Estado colombiano, sino también las realidades del territorio como lo es el porcentaje de crecimiento del grupo de mujeres: De acuerdo con las proyecciones de crecimiento poblacional (DANE, 2005), para 2011, las mujeres representarían el 50,6% de la población total colombiana, equivalente a 23.313.302 millones de mujeres, frente a 22.731.299 millones de hombres que representarían el 49,4%. Con una mayor concentración en las zonas urbanas, con el 75,6%. Con base en las anteriores consideraciones, es fundamental traer a colación a la población femenina que abarca más del 50% de la población colombiana. Por lo tanto, es pertinente el presente trabajo de grado al tener como principal énfasis las políticas públicas del Estado colombiano para las mujeres enfocadas en el área del emprendimiento, ya que su potencialización llevaría al Estado a contar con una herramienta para la erradicación de la pobreza y lograr un país más equitativo no solo desde la formulación de políticas sino en su implementación. Se hace necesario, en un primer momento, identificar los principales debates teóricos sobre la relación de las mujeres y su participación política en cuanto al emprendimiento y a la construcción social de país. En contraposición a los enfoques institucionales que han posicionado a la mujer desde un paradigma asistencialista, seguido por uno de riesgo, vulnerabilidad y violencia, para, finalmente, llegar a un enfoque de desarrollo integral. El análisis se presenta en el primer capítulo. En un segundo momento, es decir el capítulo dos, se presentará el componente teórico del desarrollo del emprendimiento en Colombia. Posteriormente, en el tercer capítulo, se analizarán las entrevistas realizadas a mujeres emprendedoras de los diferentes niveles sociales y a hombres, empleados y funcionarios tanto del sector público como privado. El análisis da cuenta de la influencia de las políticas públicas de emprendimiento, al tener como punto de referencia las relaciones instituciones estatales como mujer emprendedora y sus relaciones dentro de organizaciones y cómo esto repercute en su participación política y en la construcción del desarrollo social en Colombia. Se identificarán, igualmente, las causas y variables que impiden llevar a la realidad las políticas públicas de emprendimiento en clave de género y así medir o cualificar la manera en que el Estado colombiano aporta al desarrollo de los emprendimientos de las mujeres en el periodo 2000 – 2018.The formulation of differentiated public policies is based not only on the international demands to which the Colombian State has accepted, but also on the realities of the territory, as is the percentage of growth of the group of women: According to the projections of population growth (DANE, 2005), for 2011, women would represent 50.6% of the total Colombian population, equivalent to 23,313,302 million women, compared to 22,731,299 million men who would represent 49.4%. With a greater concentration in urban areas, with 75.6%. Based on the above considerations, it is essential to bring up the female population that covers more than 50% of the Colombian population. Therefore, the present degree work is relevant, having as main emphasis the public policies of the Colombian State for women focused in the area of entrepreneurship, because that potentialization would lead the State to have a tool for the eradication of poverty and achieve a more equitable country not only from the formulation of policies, but also in its implementation. It is necessary, at first, to identify the main theoretical debates on the relationship of women and their political participation in terms of entrepreneurship and the social construction of the country. In contrast to the institutional approaches that have positioned women from a welfare paradigm, followed by one of risk, vulnerability and violence, to finally reach an integral development approach. The analysis is presented in the first chapter. In a second moment, that is to say chapter two, the theoretical component of the development of entrepreneurship in Colombia will be presented. Subsequently, in the third chapter, the interviews conducted with women entrepreneurs from different social levels and men, employees and officials from both the public and private sectors will be analyzed. The analysis explains of the influence of public policies on entrepreneurship, having as a point of reference the relations between state institutions as an entrepreneur and their relationships within organizations and how this affects their political participation and the construction of social development in Colombia. It will also identify the causes and variables that prevent the realization of public policies of entrepreneurship in terms of gender and thus measure or qualify the way in which the Colombian State contributes to the development of women's enterprises in the period 2000 - 2018Magíster en Estudios PolíticosMaestrí

Universality of clone dynamics during tissue development.

The emergence of complex organs is driven by the coordinated proliferation, migration and differentiation of precursor cells. The fate behaviour of these cells is reflected in the time evolution their progeny, termed clones, which serve as a key experimental observable. In adult tissues, where cell dynamics is constrained by the condition of homeostasis, clonal tracing studies based on transgenic animal models have advanced our understanding of cell fate behaviour and its dysregulation in disease (1, 2). But what can be learned from clonal dynamics in development, where the spatial cohesiveness of clones is impaired by tissue deformations during tissue growth? Drawing on the results of clonal tracing studies, we show that, despite the complexity of organ development, clonal dynamics may converge to a critical state characterized by universal scaling behaviour of clone sizes. By mapping clonal dynamics onto a generalization of the classical theory of aerosols, we elucidate the origin and range of scaling behaviours and show how the identification of universal scaling dependences may allow lineage-specific information to be distilled from experiments. Our study shows the emergence of core concepts of statistical physics in an unexpected context, identifying cellular systems as a laboratory to study non-equilibrium statistical physics.Wellcome Trus

Early lineage restriction in temporally distinct populations of Mesp1 progenitors during mammalian heart development.

Cardiac development arises from two sources of mesoderm progenitors, the first heart field (FHF) and the second (SHF). Mesp1 has been proposed to mark the most primitive multipotent cardiac progenitors common for both heart fields. Here, using clonal analysis of the earliest prospective cardiovascular progenitors in a temporally controlled manner during early gastrulation, we found that Mesp1 progenitors consist of two temporally distinct pools of progenitors restricted to either the FHF or the SHF. FHF progenitors were unipotent, whereas SHF progenitors were either unipotent or bipotent. Microarray and single-cell PCR with reverse transcription analysis of Mesp1 progenitors revealed the existence of molecularly distinct populations of Mesp1 progenitors, consistent with their lineage and regional contribution. Together, these results provide evidence that heart development arises from distinct populations of unipotent and bipotent cardiac progenitors that independently express Mesp1 at different time points during their specification, revealing that the regional segregation and lineage restriction of cardiac progenitors occur very early during gastrulation.This is the author's accepted manuscript and will be under embargo until the 24th of February 2015. The final version is published by NPG in Nature Cell Biology here: http://www.nature.com/ncb/journal/v16/n9/full/ncb3024.html

Defining the Regional and Lineage Contribution of Early Mesp1 Cardiovascular Progenitors During Mammalian Heart Development

The heart arises from two sources of mesoderm progenitors, the first (FHF) and the second heart field (SHF) progenitors. Mesp1 has been proposed to mark the most primitive multipotent cardiac progenitors (MCPs) common for both heart fields. However, it remains unclear whether at the single cell level, Mesp1 progenitors represent a common progenitor for the FHF and SHF. Using mosaic tracing and inducible clonal analysis with a multicolor reporter strategy, we investigated the contribution of Mesp1 cardiovascular progenitors in a temporally controlled manner during the early gastrulation. Our data indicated that the myocardium derives from ~250 Mesp1 expressing cardiac progenitors born during gastrulation. Temporal analysis of clonally labeled Mesp1 cells revealed the existence of temporally distinct populations of Mesp1 progenitors that are restricted to either the FHF or the SHF. FHF progenitors were unipotent, while SHF progenitors, were either uni- or bipotent. Microarray and single cell RT-PCR analysis of Mesp1 progenitors revealed the existence of molecularly distinct populations of Mesp1 progenitors, consistent with their lineage and regional contribution. Moreover biophysical analysis of clonal data revealed that, despite arising at different time points and contributing to different heart regions, the temporally distinct cardiac progenitors present very similar clonal dynamics. Altogether, these results provide insights into the number of cardiac progenitors and their mode of growth. Moreover they provide evidence that heart development arises from distinct populations of unipotent and bipotent cardiac progenitors expressing Mesp1 independently at different time points during gastrulation. Our data reveal that the regional segregation and lineage restriction of cardiac progenitors occurs very early during embryonic development.Doctorat en Sciences biomédicales et pharmaceutiques (Médecine)info:eu-repo/semantics/nonPublishe

Potassium content of irradiated packed red blood cells in different storage media: Is there a need for additive solution-dependent recommendations for infant transfusion?

Prevention of transfusion-associated graft versus host disease (TA-GVHD) by gamma irradiation is known to induce increased K+ in supernatant of packed red blood cells (PRBCs) stored in CPDA-1 and SAGM conservative solutions. However, no data exist for PRBCs in AS-3 medium which is considered safe for neonatal transfusion. We evaluated haemolysis and K+ release from irradiated AS-3 PRBCs and compared our results with reported data for SAGM and CPDA-1 PRBCs. Our results indicate that irradiated PRBCs stored in AS-3 after more than 7days post-irradiation should not be used in massive and/or rapidly infused transfusions in neonates and infants.JOURNAL ARTICLESCOPUS: ar.jinfo:eu-repo/semantics/publishe

Defining the earliest step of cardiovascular progenitor specification during embryonic stem cell differentiation.

During embryonic development and embryonic stem cell (ESC) differentiation, the different cell lineages of the mature heart arise from two types of multipotent cardiovascular progenitors (MCPs), the first and second heart fields. A key question is whether these two MCP populations arise from differentiation of a common progenitor. In this paper, we engineered Mesp1-green fluorescent protein (GFP) ESCs to isolate early MCPs during ESC differentiation. Mesp1-GFP cells are strongly enriched for MCPs, presenting the ability to differentiate into multiple cardiovascular lineages from both heart fields in vitro and in vivo. Transcriptional profiling of Mesp1-GFP cells uncovered cell surface markers expressed by MCPs allowing their prospective isolation. Mesp1 is required for MCP specification and the expression of key cardiovascular transcription factors. Isl1 is expressed in a subset of early Mesp1-expressing cells independently of Mesp1 and acts together with Mesp1 to promote cardiovascular differentiation. Our study identifies the early MCPs residing at the top of the cellular hierarchy of cardiovascular lineages during ESC differentiation.Journal ArticleResearch Support, Non-U.S. Gov'tSCOPUS: ar.jinfo:eu-repo/semantics/publishe