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

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

Clonal analysis of Notch1-expressing cells reveals the existence of unipotent stem cells that retain long-term plasticity in the embryonic mammary gland.

Recent lineage tracing studies have revealed that mammary gland homeostasis relies on unipotent stem cells. However, whether and when lineage restriction occurs during embryonic mammary development, and which signals orchestrate cell fate specification, remain unknown. Using a combination of in vivo clonal analysis with whole mount immunofluorescence and mathematical modelling of clonal dynamics, we found that embryonic multipotent mammary cells become lineage-restricted surprisingly early in development, with evidence for unipotency as early as E12.5 and no statistically discernable bipotency after E15.5. To gain insights into the mechanisms governing the switch from multipotency to unipotency, we used gain-of-function Notch1 mice and demonstrated that Notch activation cell autonomously dictates luminal cell fate specification to both embryonic and basally committed mammary cells. These functional studies have important implications for understanding the signals underlying cell plasticity and serve to clarify how reactivation of embryonic programs in adult cells can lead to cancer.Wellcome Trus

Identification of Lineage-Uncommitted, Long-Lived, Label-Retaining Cells in Healthy Human Esophagus and Stomach, and in Metaplastic Esophagus

Background & Aims The existence of slowly cycling, adult stem cells has been challenged by the identification of actively cycling cells. We investigated the existence of uncommitted, slowly cycling cells by tracking 5-iodo-2'-deoxyuridine (IdU) label-retaining cells (LRCs) in normal esophagus, Barrett's esophagus (BE), esophageal dysplasia, adenocarcinoma, and healthy stomach tissues from patients. Methods Four patients (3 undergoing esophagectomy, 1 undergoing esophageal endoscopic mucosal resection for dysplasia and an esophagectomy for esophageal adenocarcinoma) received intravenous infusion of IdU (200 mg/m2 body surface area; maximum dose, 400 mg) over a 30-minute period; the IdU had a circulation half-life of 8 hours. Tissues were collected at 7, 11, 29, and 67 days after infusion, from regions of healthy esophagus, BE, dysplasia, adenocarcinoma, and healthy stomach; they were analyzed by in situ hybridization, flow cytometry, and immunohistochemical analyses. Results No LRCs were found in dysplasias or adenocarcinomas, but there were significant numbers of LRCs in the base of glands from BE tissue, in the papillae of the basal layer of the esophageal squamous epithelium, and in the neck/isthmus region of healthy stomach. These cells cycled slowly because IdU was retained for at least 67 days and co-labeling with Ki-67 was infrequent. In glands from BE tissues, most cells did not express defensin-5, Muc-2, or chromogranin A, indicating that they were not lineage committed. Some cells labeled for endocrine markers and IdU at 67 days; these cells represented a small population (<0.1%) of epithelial cells at this time point. The epithelial turnover time of the healthy esophageal mucosa was approximately 11 days (twice that of the intestine). Conclusions LRCs of human esophagus and stomach have many features of stem cells (long lived, slow cycling, uncommitted, and multipotent), and can be found in a recognized stem cell niche. Further analyses of these cells, in healthy and metaplastic epithelia, is required

Corneal Limbal Microenvironment Can Induce Transdifferentiation of Hair Follicle Stem Cells into Corneal Epithelial-like Cells

The aim of this study was to investigate the transdifferentiation potential of murine vibrissa hair follicle (HF) stem cells into corneal epithelial-like cells through modulation by corneal- or limbus-specific microenvironmental factors. Adult epithelial stem cells were isolated from the HF bulge region by mechanical dissection or fluorescence-activated cell sorting using antibodies to α6 integrin, enriched by clonal expansion, and subcultivated on various extracellular matrices (type IV collagen, laminin-1, laminin-5, fibronectin) and in different conditioned media derived from central and peripheral corneal fibroblasts, limbal stromal fibroblasts, and 3T3 fibroblasts. Cellular phenotype and differentiation were evaluated by light and electron microscopy, real-time reverse transcription-polymerase chain reaction, immunocytochemistry, and Western blotting, using antibodies against putative stem cell markers (K15, α6 integrin) and differentiation markers characteristic for corneal epithelium (K12, Pax6) or epidermis (K10). Using laminin-5, a major component of the corneo-limbal basement membrane zone, and conditioned medium from limbal stromal fibroblasts, clonally enriched HF stem and progenitor cells adhered rapidly and formed regularly arranged stratified cell sheets. Conditioned medium derived from limbal fibroblasts markedly upregulated expression of cornea-specific K12 and Pax6 on the mRNA and protein level, whereas expression of the epidermal keratinocyte marker K10 was strongly downregulated. These findings suggest that adult HF epithelial stem cells are capable of differentiating into corneal epithelial-like cells in vitro when exposed to a limbus-specific microenvironment. Therefore, the HF may be an easily accessible alternative therapeutic source of autologous adult stem cells for replacement of the corneal epithelium and restoration of visual function in patients with ocular surface disorders

p63 regulates Satb1 to control tissue-specific chromatin remodeling during development of the epidermis

Genome organizer Satb1 is regulated by p63 and contributes to epidermal morphogenesis by remodeling chromatin structure and gene expression at the epidermal differentiation complex locus

Diversification of Peptidomimetics and Oligopeptides through Microwave-Assisted Rhodium(III)-Catalyzed Intramolecular Annulation

status: publishe