Research from the Fidanza Lab at the Centre for Regenerative Medicine describes a new system to activate genes within pluripotent stem cells to encourage them to become better blood progenitor cells. P. Petazzi, T. Ventura, F. Paola Luongo, H. McClafferty, A. May, H.A. Taylor, M.J. Shipston, N. Romanò, L.M. Forrester, P. Menendez, A. Fidanza (2024) A novel human pluripotent stem cell gene activation system identifies IGFBP2 as a mediator in the production of haematopoietic progenitors in vitro eLife 13:RP94884. This new method of gene activation enabled the discovery of a new molecule that might improve the production of blood stem cells in the laboratory. Blood stem cells are used to treat blood and bone marrow disorders and patients recovering from cancer treatment. However, these procedures are reliant on a limited blood donor supply and donor matches. Production of blood cells in the laboratory from pluripotent stem cells (cells with the ability to generate all specialised cell types in an organism) could provide an alternative source for the treatment of disease. Blood progenitors (cells that are capable of differentiating into all the mature blood cell types) can be produced from pluripotent stem cells. A major issue in stem cell biology is producing fully functional blood stem cells from induced pluripotent stem cells (iPSCs) to use in cell therapy, drug screening and disease modelling. This research developed a new strategy using CRISPR activation (iCRISPRa) to drive the expression of multiple transcription factors (TFs) that play a key role in the creation of haematopoietic progenitor cells. It identified a key role for the transcription factor IGFBP2 in this process. CRISPR stands for Clustered Regularly Interspaced Short Palindromic Repeats. It is a method for gene editing that uses small sections of repeated patterns of genetic code (e.g. AAAGAAA) that researchers can add in to DNA to guide an enzyme to a desired location to cut it. It is sometimes called ‘molecular scissors’ and is a very accurate way to turn off specific genes in living cells. As well as providing fundamental new insights into the mechanisms of haematopoietic differentiation, the broader applicability of iCRISPRa provides a valuable tool for studying dynamic processes in development as well as producing abnormal cells for study on a wide range of systems. Our work establishes a novel inducible genetic tool to activate endogenous gene expression in human pluripotent stem cells that can now be used on any cell type. We used the iSAM system to identify IGFBP2 as a new mediator of human blood cell development, and in the same way, it can now be used by many other labs. Antonella Fidanza Lead Researcher P. Petazzi, T. Ventura, F. Paola Luongo, H. McClafferty, A. May, H.A. Taylor, M.J. Shipston, N. Romanò, L.M. Forrester, P. Menendez, A. Fidanza (2024) A novel human pluripotent stem cell gene activation system identifies IGFBP2 as a mediator in the production of haematopoietic progenitors in vitro eLife 13:RP94884. Antonella Fidanza obtained her PhD in Biotechnology of Reproduction in Italy before joining the Centre for Regenerative Medicine (CRM) in 2014 for her postdoctoral training in the Forrester Lab. In 2023, she established her lab in human in vitro hematopoiesis, where she uses a multidisciplinary approach to understand how human blood cells develop during gestation using pluripotent stem cells as model. This work results from collaborations with the Menendez lab at the Josep Carreras Leukaemia Research Institute in Barcelona and the Shipston lab at the Institute of Neuroscience and Cardiovascular Research at the University of Edinburgh. Fidanza Group research page Paper - A novel human pluripotent stem cell gene activation system identifies … Publication date 17 Feb, 2025
