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Targeted CRISPR-Cas9 screening identifies core transcription factors controllin...

Teske, Michael; Wertheimer, Tobias; Butz, Stefan; Zwicky, Pascale; Mallona, Izaskun; Nopper, Svenja L.; Münz, Christian; Elling, Ulrich

During development, blood generation begins in the yolk sac with the differentiation of haemato-endothelial mesoderm forming haematopoietic progenitors. This study aims to identify the crucial molecular regulators of haemato-endothelial mesoderm formation and to extend our knowledge of the process in an unbiased way. We employ a murine embryonic stem cell model that recapitulates embryonic blood development, an...


Gene reactivation upon erosion of X chromosome inactivation in female hiPSCs is...

Raposo, Ana Cláudia; Caldas, Paulo; Jeremias, Joana; Arez, Maria; Mateus, Francisca Cazaux; Barbosa, Pedro; Sousa-Luís, Rui; Água, Frederico

Female human induced pluripotent stem cells frequently undergo X-chromosome inactivation (XCI) erosion, marked by X-inactive specific transcript (XIST) RNA loss and partial reactivation of the inactive X (Xi). This overlooked phenomenon limits our understanding of its impact on stem cell applications. Here, we show that XCI erosion is frequent and heterogeneous, leading to the reactivation of several X-linked g...


Targeted CRISPR-Cas9 screening identifies core transcription factors controllin...

Teske, Michael; Wertheimer, Tobias; Butz, Stefan; Zwicky, Pascale; Mallona, Izaskun; Nopper, Svenja L; Münz, Christian; Elling, Ulrich

During development, blood generation begins in the yolk sac with the differentiation of haemato-endothelial mesoderm forming haematopoietic progenitors. This study aims to identify the crucial molecular regulators of haemato-endothelial mesoderm formation and to extend our knowledge of the process in an unbiased way. We employ a murine embryonic stem cell model that recapitulates embryonic blood development, an...


Gene reactivation upon erosion of X chromosome inactivation in female hiPSCs is...

Raposo, Ana Cláudia; Caldas, Paulo; Jeremias, Joana; Arez, Maria; Cazaux Mateus, Francisca; Barbosa, Pedro; Sousa-Luis, Rui; Água, Frederico

Female human induced pluripotent stem cells frequently undergo X-chromosome inactivation (XCI) erosion, marked by X-inactive specific transcript (XIST) RNA loss and partial reactivation of the inactive X (Xi). This overlooked phenomenon limits our understanding of its impact on stem cell applications. Here, we show that XCI erosion is frequent and heterogeneous, leading to the reactivation of several X-linked g...


Unraveling the biological potential of skin fibroblast

Pascoal, Carlota; Granjo, Pedro; Mexia, Patrícia; Gallego, Diana; Lourenço, Rita Adubeiro; Sharma, Shally; Pérez, Bélen; Castro-Caldas, Margarida

Objective: In this study, we examined the molecular response of human skin fibroblasts to an inflammatory cytokine to evaluate their suitability as models for immunopathology research. Methods: Skin fibroblasts were stimulated with tumour necrosis factor (TNF)-α, and the transcriptome was profiled via RNA-Seq. The differentially expressed genes were screened to predict immunological pathways and interactions. T...


Genetic and microenvironmental intra-tumor heterogeneity impacts colorectal can...

Sobral, Daniel; Martins, Marta; Kaplan, Shannon; Golkaram, Mahdi; Salmans, Michael; Khan, Nafeesa; Vijayaraghavan, Raakhee; Casimiro, Sandra

Colorectal cancer (CRC) is a highly diverse disease, where different genomic instability pathways shape genetic clonal diversity and tumor microenvironment. Although intra-tumor heterogeneity has been characterized in primary tumors, its origin and consequences in CRC outcome is not fully understood. Therefore, we assessed intra- and inter-tumor heterogeneity of a prospective cohort of 136 CRC samples. We demon...


Genetic predisposition for aggressive behaviour related with dopamine and serot...

Paulino, Cathy; Fernandes, Alexandra R.; Baptista, Pedro V.; Soeiro, Cristina; Grosso, Ana Rita; Quintas, Alexandre


The genetic susceptibility linking preterm birth and periodontal disease : a re...

Couceiro, Joana; Grosso, Ana Rita; Baptista, Pedro V.; Mendes, José João; Fernandes, Alexandra R.; Quintas, Alexandre


Control of endothelial quiescence by FOXO-regulated metabolites

Andrade, Jorge; Shi, Chenyue; Costa, Ana S. H.; Choi, Jeongwoon; Kim, Jaeryung; Doddaballapur, Anuradha; Sugino, Toshiya; Ong, Yu Ting; Castro, Marco

Endothelial cells (ECs) adapt their metabolism to enable the growth of new blood vessels, but little is known how ECs regulate metabolism to adopt a quiescent state. Here, we show that the metabolite S-2-hydroxyglutarate (S-2HG) plays a crucial role in the regulation of endothelial quiescence. We find that S-2HG is produced in ECs after activation of the transcription factor forkhead box O1 (FOXO1), where it li...


Overexpression of wild-type IL-7Rα promotes T-cell acute lymphoblastic leukemia...

Silva, Ana; Almeida, Afonso; Cachucho, Ana; Neto, João Luís; Demeyer, Sofie; Ramos De Matos, Mafalda; Hogan, Thea; Li, Yunlei; Meijerink, Jules

Tight regulation of IL-7Rα expression is essential for normal T-cell development. IL-7Rα gain-of-function mutations are known drivers of T-cell acute lymphoblastic leukemia (T-ALL). Although a subset of patients with T-ALL display high IL7R messenger RNA levels and cases with IL7R gains have been reported, the impact of IL-7Rα overexpression, rather than mutational activation, during leukemogenesis remains uncl...


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