Epithelial to mesenchymal transition trajectories in developmental and disease

Resumen del trabajo presentado al 19th International Congress of Developmental Biology, celebrado en El Algarve (Portugal) del 16 al 20 de octubre de 2022.The Epithelial to Mesenchymal transition (EMT) triggers cell plasticity during embryonic development and tissue repair, but it can also promote tumor progression and organ degeneration. The reactivation of EMT in the adult promotes cell dedifferentiation and profound remodeling of the epithelial program, leading to multiple phenotypes, observed in response to injury, during organ fibrosis and cancer cell dissemination. Despite recent advances, identifying universal EMT molecular signatures and understanding how EMT can instructs different outcomes have remained elusive due to the intrinsic complexity and heterogeneity of the process. We have dissected how EMT transcription factors (EMT-TFs) orchestrate TGFBinduced EMT including phenotypic and behavioral states. Further, we have combined lineage tracing and single-cell transcriptomics in three EMT contexts, namely the neural crest, renal fibrosis, and breast cancer to reveal conserved EMT transcription factor codes and signaling pathways that discriminate different EMT states. After inferring cellular trajectories, we have reconstructed the evolution of EMT phenotypic and functional states in all these contexts. Finally, multiplex labeling allowed to spatially allocate distinct EMT programs in mouse and human tumor samples. Altogether, this work unveils distinct EMT trajectories in development and disease, which should also help propase improved therapeutic strategies for organ fibrosis and cancer.Peer reviewe

Two distinct epithelial to mesenchymal transition programmes. Control invasion and inflammation in segregated tumour cell populations

Resumen del trabajo presentado al 19th Christmas Meeting del Instituto de Neurociencias (CSIC-UMH) celebrado el 21 de diciembre de 2022.Epithelial plasticity is at the core of crucial processes including embryonic cell migration, cancer progression, organ tibrosis and tissue repair. The epithelial to mesenchymal transition (EMT) triggers cell plasticity in all these contexts, highlighting its pleiotropy and intrinsic complcxity. Seminal studies have classified EMT states in cancer celllines and animal modcls. This varicty ofEMT phenotypes necds further investigation, particularly those relevant to the progression ofprevalent and dcvastating diseases such as cancer. Our objcctive is to analyse at single-cell level how different EMT states are established in tumours and if different EMT states pcrform different functions during tumour progression.Peer reviewe

EMT-TFs gene regulatory landscape during normal development and in pathological contexts

Trabajo presentado al Seminario de Unidad Neurobiología Celular y de Sistemas del Instituto de Neurociencias, celebrado online el 2 de noviembre de 2021.Peer reviewe

EMT- associated Gene Regulatory Networks in development and disease

Resumen del trabajo presentado al 19th International Congress of Developmental Biology, celebrado en El Algarve (Portugal) del 16 al 20 de octubre de 2022.Epithelial cells lose their apico-basal polarity and cell-cell adhesion properties when undergoing phenotypic changes associated with the Epithelial to Mesenchymal Transition (EMT), which helps them to acquire a migratory behaviour. EMT plays an important role during embryonic development and adult disease progression, including cancer and fibrosis (Nieto, 2016). The Neural Crest (NC) is the best studied model of developmental EMT programmes. NC cells are multipotent embryonic progenitors, which delaminate from the neural tu be during late gastrulation stages of vertebrate embryonic development. By undergoing EMT, NC cells migrate to different parts of embryo where they give rise to different tissues. The EMT develops as a series of molecular events, where the expression of many genes is spatiotemporally regulated by different mechanisms including transcriptional changes, epigenetic regulation and activation of miRNAs, among others. Key players are the so called EMT transcription factors (EMT-TFs), including Snail, Zeb, Twist and Prrx families, which initiate and/or maintain EMT and, when downregulated, can revert the programme. Regulation of target genes by the EMT-TFs leads to the existence of gene regulatory networks (GRNs). We have studied the EMT programme using in-house generated as well as publicly available scRNA-seq data from neural crest and models of cancer and fibrosis. Furthermore, we are building scRNA-Seq based EMT-specific GRNs also inferring both commonalities and specificities in the different contexts to get further insight into this pleiotropic programme that shapes the embryo and favours the progression of devastating diseases.Peer reviewe

A case of Occupational Methemoglobinemia (MetHb): A Rare Entity and Unique Treatment

Methemoglobinemia is acute emergency which have precise and effective treatment if instituted in time. Methemoglobinemia due to chemical exposure is a known entity. But it required a high index of suspicion to look for it in busy casualty. Treatment with methylene blue is safe and truly lifesaving if instituted in time. Here we are presenting a case of Occupational methemoglobinemia who was treated successfully

Evaluation of Maize for Different Methods and Levels of Zinc Application

The different methods of zinc (Zn) application with various doses were studied in maize (Zea mays L.).The methodsadopted namely, seed priming (1, 2 and 3%), seed treatment (2, 4 and 6 g kg-1 seed), soil application (4, 6 and 8kg ha-1) and foliar application (0.25, 0.50 and 0.75%) with three levels of each. Foliar application of Zn at 0.75%has exhibited phytotoxicity initially but later the phytotoxicity disappeared after 8-10 days. Irrespective of theZn application method and level growth, yield, Zn content and quality of maize was significantly enhanced overabsolute control. Seed treatment was found to be the cheapest Zn application method. Seed treatment of Znat 4 g kg-1produced highest maize grain yield, net returns, and the maize grains were enriched with Zn and weresuitable for human consumption as a biofortified Zn source. Maximum residual elemental Zn in soil was found dueto foliar application of Zn at 0.75%. However, seed treatment of Zn at 4 g kg-1resulted suitable for an eco-friendlyand sustainable method of Zn application for agronomic packages and practices

Comparative transcriptome analyses in contrasting onion (Allium cepa L.) genotypes for drought stress.

Onion (Allium cepa L.) is an important vegetable crop widely grown for diverse culinary and nutraceutical properties. Being a shallow-rooted plant, it is prone to drought. In the present study, transcriptome sequencing of drought-tolerant (1656) and drought-sensitive (1627) onion genotypes was performed to elucidate the molecular basis of differential response to drought stress. A total of 123206 and 139252 transcripts (average transcript length: 690 bases) were generated after assembly for 1656 and 1627, respectively. Differential gene expression analyses revealed upregulation and downregulation of 1189 and 1180 genes, respectively, in 1656, whereas in 1627, upregulation and downregulation of 872 and 1292 genes, respectively, was observed. Genes encoding transcription factors, cytochrome P450, membrane transporters, and flavonoids, and those related to carbohydrate metabolism were found to exhibit a differential expression behavior in the tolerant and susceptible genotypes. The information generated can facilitate a better understanding of molecular mechanisms underlying drought response in onion