9 documents found, page 1 of 1
Restoring tumor immunogenicity with dendritic cell reprogramming
Zimmermannova, Olga; Ferreira, Alexandra G.; Ascic, Ervin; Velasco Santiago, Marta; Kurochkin, Ilia; Hansen, Morten; Met, Özcan; Caiado, InêsDecreased antigen presentation contributes to the ability of cancer cells to evade the immune system. We used the minimal gene regulatory network of type 1 conventional dendritic cells (cDC1) to reprogram cancer cells into professional antigen-presenting cells (tumor-APCs). Enforced expression of the transcription factors PU.1, IRF8, and BATF3 (PIB) was sufficient to induce the cDC1 phenotype in 36 cell lines d...
GATA2 mitotic bookmarking is required for definitive haematopoiesis
Silvério-Alves, Rita; Kurochkin, Ilia; Rydström, Anna; Vazquez Echegaray, Camila; Haider, Jakob; Nicholls, Matthew; Rode, Christina; Thelaus, LouiseIn mitosis, most transcription factors detach from chromatin, but some are retained and bookmark genomic sites. Mitotic bookmarking has been implicated in lineage inheritance, pluripotency and reprogramming. However, the biological significance of this mechanism in vivo remains unclear. Here, we address mitotic retention of the hemogenic factors GATA2, GFI1B and FOS during haematopoietic specification. We show ...
High-Throughput Drug Screening Revealed That Ciclopirox Olamine Can Engender Ga...
Pádua, Diana; Figueira, Paula; Pinto, Mariana; Maia, André Filipe; Peixoto, Joana; Lima, Raquel T; Pombinho, António; Pereira, Carlos FilipeCancer stem cells (CSCs) are relevant therapeutic targets for cancer treatment. Still, the molecular circuits behind CSC characteristics are not fully understood. The low number of CSCs can sometimes be an obstacle to carrying out assays that explore their properties. Thus, increasing CSC numbers via small molecule-mediated cellular reprogramming appears to be a valid alternative tool. Using the SORE6-GFP repor...
HMGA1 Has Predictive Value in Response to Chemotherapy in Gastric Cancer
Pádua, Diana; Pinto, Débora Filipa; Figueira, Paula; Pereira, Carlos Filipe; Almeida, Raquel; Mesquita, PatríciaGastric cancer is a serious health problem worldwide. Although its incidence is decreasing, the five-year survival rate remains low. Thus, it is essential to identify new biomarkers that could promote better diagnosis and treatment of patients with gastric cancer. High-mobility group AT-hook 1 (HMGA1) is a non-histone, chromatin-binding protein that has been found overexpressed in several tumor types. It has be...
Cell Fate Reprogramming in the Era of Cancer Immunotherapy
Zimmermannova, Olga; Caiado, Inês; Ferreira, Alexandra G.; Pereira, Carlos FilipeAdvances in understanding how cancer cells interact with the immune system allowed the development of immunotherapeutic strategies, harnessing patients' immune system to fight cancer. Dendritic cell-based vaccines are being explored to reactivate anti-tumor adaptive immunity. Immune checkpoint inhibitors and chimeric antigen receptor T-cells (CAR T) were however the main approaches that catapulted the therapeut...
A SOX2 Reporter System Identifies Gastric Cancer Stem-Like Cells Sensitive to M...
Pádua, Diana; Barros, Rita; Amaral, Ana Luísa; Mesquita, Patrícia; Freire, Ana Filipa; Sousa, Mafalda; Maia, André Filipe; Caiado, Inês; Fernandes, HugoGastric cancer remains a serious health burden with few therapeutic options. Therefore, the recognition of cancer stem cells (CSCs) as seeds of the tumorigenic process makes them a prime therapeutic target. Knowing that the transcription factors SOX2 and OCT4 promote stemness, our approach was to isolate stem-like cells in human gastric cancer cell lines using a traceable reporter system based on SOX2/OCT4 acti...
Understanding and Modulating Immunity With Cell Reprogramming
Pires, Cristiana Ferreira; Rosa, Fábio F.; Kurochkin, Ilia; Pereira, Carlos FilipeCell reprogramming concepts have been classically developed in the fields of developmental and stem cell biology and are currently being explored for regenerative medicine, given its potential to generate desired cell types for replacement therapy. Cell fate can be experimentally reversed or modified by enforced expression of lineage specific transcription factors leading to pluripotency or attainment of anothe...
Cooperative Transcription Factor Induction Mediates Hemogenic Reprogramming
Gomes, Andreia; Kurochkin, Ilia; Chang, Betty; Daniel, Michael; Law, Kenneth; Satija, Namita; Lachmann, Alexander; Wang, Zichen; Ferreira, LinoDuring development, hematopoietic stem and progenitor cells (HSPCs) arise from specialized endothelial cells by a process termed endothelial-to-hematopoietic transition (EHT). The genetic program driving human HSPC emergence remains largely unknown. We previously reported that the generation of hemogenic precursor cells from mouse fibroblasts recapitulates developmental hematopoiesis. Here, we demonstrate that ...
Transient HES5 Activity Instructs Mesodermal Cells toward a Cardiac Fate
Freire, Ana G.; Waghray, Avinash; Soares-da-Silva, Francisca; Resende, Tatiana P.; Lee, Dung-Fang; Pereira, Carlos Filipe; Nascimento, Diana S.Notch signaling plays a role in specifying a cardiac fate but the downstream effectors remain unknown. In this study we implicate the Notch downstream effector HES5 in cardiogenesis. We show transient Hes5 expression in early mesoderm of gastrulating embryos and demonstrate, by loss and gain-of-function experiments in mouse embryonic stem cells, that HES5 favors cardiac over primitive erythroid fate. Hes5 overe...