Macrophages provide a transient muscle stem cell niche via NAMPT secretion.

Skeletal muscle regenerates through the activation of resident stem cells. Termed satellite cells, these normally quiescent cells are induced to proliferate by wound-derived signals1. Identifying the source and nature of these cues has been hampered by an inability to visualize the complex cell interactions that occur within the wound. Here we use muscle injury models in zebrafish to systematically capture the interactions between satellite cells and the innate immune system after injury, in real time, throughout the repair process. This analysis revealed that a specific subset of macrophages 'dwell' within the injury, establishing a transient but obligate niche for stem cell proliferation. Single-cell profiling identified proliferative signals that are secreted by dwelling macrophages, which include the cytokine nicotinamide phosphoribosyltransferase (Nampt, which is also known as visfatin or PBEF in humans). Nampt secretion from the macrophage niche is required for muscle regeneration, acting through the C-C motif chemokine receptor type 5 (Ccr5), which is expressed on muscle stem cells. This analysis shows that in addition to their ability to modulate the immune response, specific macrophage populations also provide a transient stem-cell-activating niche, directly supplying proliferation-inducing cues that govern the repair process that is mediated by muscle stem cells. This study demonstrates that macrophage-derived niche signals for muscle stem cells, such as NAMPT, can be applied as new therapeutic modalities for skeletal muscle injury and disease.

Repression of Igf1 expression by Ezh2 prevents basal cell differentiation in the developing lung.

Epigenetic mechanisms involved in the establishment of lung epithelial cell lineage identities during development are largely unknown. Here, we explored the role of the histone methyltransferase Ezh2 during lung lineage determination. Loss of Ezh2 in the lung epithelium leads to defective lung formation and perinatal mortality. We show that Ezh2 is crucial for airway lineage specification and alveolarization. Using optical projection tomography imaging, we found that branching morphogenesis is affected in Ezh2 conditional knockout mice and the remaining bronchioles are abnormal, lacking terminally differentiated secretory club cells. Remarkably, RNA-seq analysis revealed the upregulation of basal genes in Ezh2-deficient epithelium. Three-dimensional imaging for keratin 5 further showed the unexpected presence of a layer of basal cells from the proximal airways to the distal bronchioles in E16.5 embryos. ChIP-seq analysis indicated the presence of Ezh2-mediated repressive marks on the genomic loci of some but not all basal genes, suggesting an indirect mechanism of action of Ezh2. We found that loss of Ezh2 de-represses insulin-like growth factor 1 (Igf1) expression and that modulation of IGF1 signaling ex vivo in wild-type lungs could induce basal cell differentiation. Altogether, our work reveals an unexpected role for Ezh2 in controlling basal cell fate determination in the embryonic lung endoderm, mediated in part by repression of Igf1 expression.

The needed link between open science and science diplomacy-A Latin American perspective.

The relevance of science diplomacy and open science in today's world is undeniable. Science diplomacy enables countries to jointly address pressing global challenges, such as climate change, pandemics, and food security. Open science, promoting accessible and transparent research, plays a pivotal role in this context. Nevertheless, the degree of openness is subject to specific circumstances, contingent upon varying factors, including local knowledge and resources. Latin America has not only been at the forefront of pioneering open access strategies, making it an interesting case to study, but it has also shown a tangible interest in using science diplomacy. Our research employs a mixed-methods approach, incorporating a quantitative survey involving 50 organizations and initiatives dedicated to promoting open science in Latin America, along with two qualitative focus group studies. Our primary objective is to assess if and how these entities use science diplomacy to achieve their objectives. Non-policy entities were prioritized due to their institutional stability in the region. We highlight successful strategies and delve into the existing barriers hindering the full implementation of open science principles. Our research aims to enhance collaboration between these organizations and policy and decision-makers by providing a set of recommendations in that direction. By shedding light on the current landscape and dynamics of open science in Latin America, we aspire to focus on science diplomacy, facilitate informed decision-making, and formulate policies that further propel the region along the path of openness, collaboration, and innovation in scientific research.

Organized Scientific Diaspora and Its Contributions to Science Diplomacy in Emerging Economies: The Case of Latin America and the Caribbean.

The current knowledge society has driven an unprecedented mobility of people, especially scientists, from emerging economies to developed countries. This mobility can allow the development of human talent and the access to first class infrastructure and resources, but it can also mean a loss for emerging economies due to the phenomenon of brain drain. To counteract this situation, some countries in Latin America and the Caribbean have developed models for the articulation of their scientific diaspora in projects and programs, with the aim of exchanging knowledge and capitalizing on human and technical resources to advance science, technology and innovation systems. Likewise, science diplomacy has become a tool for interlinking the work of various actors in order to advance the solution of national, transnational or global problems through scientific advice. Scientific diasporas are vital in new structures of cooperation, enabling them to innovate and solve problems jointly, advising their countries of origin and articulating policies and programs. This research seeks to analyze the interactions and initiatives identified between the organized scientific diaspora from Latin America and the Caribbean and their countries of origin in relation to science diplomacy processes, providing recommendations and proposals for public policy to improve the interaction between the diaspora and the governments of their countries of origin. Results show that diaspora organizations from Latin America and the Caribbean engage with governmental and non-state actors and are active science diplomacy stakeholders promoting the scientific developments of their country or their researchers, as well as enabling access to research resources creating alliances for scientific, institutional and academic collaborations. In the cases studied, these efforts are planned and executed by the diaspora without responding to any science diplomacy strategy of the country. Policies and programs are needed to effectively link the scientific diaspora organizations to the interests of the countries.

Transcriptome and H3K27 tri-methylation profiling of Ezh2-deficient lung epithelium.

The adaptation of the lungs to air breathing at birth requires the fine orchestration of different processes to control lung morphogenesis and progenitor cell differentiation. However, there is little understanding of the role that epigenetic modifiers play in the control of lung development. We found that the histone methyl transferase Ezh2 plays a critical role in lung lineage specification and survival at birth. We performed a genome-wide transcriptome study combined with a genome-wide analysis of the distribution of H3K27 tri-methylation marks to interrogate the role of Ezh2 in lung epithelial cells. Lung cells isolated from Ezh2-deficient and control mice at embryonic day E16.5 were sorted into epithelial and mesenchymal populations based on EpCAM expression. This enabled us to dissect the transcriptional and epigenetic changes induced by the loss of Ezh2 specifically in the lung epithelium. Here we provide a detailed description of the analysis of the RNA-seq and ChIP-seq data, including quality control, read mapping, differential expression and differential binding analyses, as well as visualisation methods used to present the data. These data can be accessed from the Gene Expression Omnibus database (super-series accession number GSE57393).