Antonella Fidanza Research Group

In vitro human hematopoiesis

Dr Antonella Fidanza

Group Leader

  • Institute for Regeneration and Repair
  • Centre for Regenerative Medicine

Contact details

We study human developmental hematopoiesis in vitro using human pluripotent stem cells (hPSCs). Pluripotent stem cells have proven to be an invaluable tool to mimic development in a dish. Our lab uses in vitro differentiation strategies to elucidate the intrinsic and extrinsic signalling driving blood development, and those signals interact to orchestrate blood development. We are particularly interested in the endothelial-to-hematopoietic transition, or EHT. In this process, a subset of endothelial cells, known as hemogenic endothelium, remodel their transcriptomic while rounding up to become a hematopoietic stem or progenitor cell. Understanding the mechanisms driving blood stem and progenitor cells development during embryonic life will improve the quality and the types of cells we can produce in the laboratory for cell therapy.

Scientific Infographic presenting the hPSCs model for human blood development.

Aims and areas of interest

Fidanza research group
Dr Antonella Fidanza and her research group

Singe-cell transcriptomics and machine learning

We have shown that in vitro differentiation of human pluripotent stem cells mimics the developmental stages leading to the formation of blood progenitors that are transcriptionally very similar to those of the embryo. Furthermore, combining machine learning with single-cell transcriptomics, we found a rare and transient population of HSC-like cells (Fidanza et al., 2020). We aim to improve the phenotype by targeting pathways and genes that we found to be different between in vitro derived HSC-like cells and functional HSCs that develop within the embryo.

Scientific infographic comparing in vitro derived HSC-like cells and functional HSCs that develop within the fetal liver. Machine learning and Artifical Neural Network allow for cell type specific comparison in vivo versus in vitro.

Transcriptional remodelling

We are particularly interested in the transcriptional control during the endothelial-to-hematopoietic transition, or EHT. We aim to understand what makes endothelial cells become hemogenic and how they progress to become blood cells. To understand the transcriptional control during this transition, we have developed an iPSCs-based endogenous gene activation CRISPR tool that we have used to remodel the gene expression (Fidanza et al., 2017; Petazzi et al., 2019; Petazzi et al., 2022). Using this approach, we want to learn the gene network important for the EHT and improve the proportion of endothelial cells that become hemogenic and eventually give rise to blood.

Scientific Infographic presenting the transition of endothelial genes to hematopoietic genes alongside cells graphic.

We believe that those who care for science share! Contact us if you want to use any of our tools/codes/datasets. If your interest in science aligns with us, get in touch. We are always looking for enthusiastic scientists, from students to postdocs.

 

Collaborators

Professor Elisa Laurenti – Cambridge Stem Cell Institute

Dr Patrick Stumpf – RWTH Aachen University

Professor Katrin Ottersbach – University of Edinburgh

Dr Nicola Romanò – University of Edinburgh

Professor Pablo Menendez – Josep Carreras Leukaemia Research Institute

Dr Raquel Espin Palazon – Iowa State University

Professor Robert Semple – University of Edinburgh

Lab members

Nora Aljindan, PhD Student

Ewen Egan, PhD Student

Maja Gabric, PhD Student

Telma Ventura, Research Assistant

 

Publications

 
 

Peer Reviewed Articles

 
 Fidanza, A. et al. (2017) ‘An all-in-one UniSam vector system for efficient gene activation’, Scientific Reports. Nature Publishing Group, 7(1), p. 6394. doi: 10.1038/s41598-017-06468-6.View Publication
 Fidanza, A. et al. (2020) ‘Single cell analyses and machine learning define hematopoietic progenitor and HSC-like cells derived from human PSCs.’, Blood. Blood, 136(25), pp. 2893–2904. doi: 10.1182/blood.2020006229.View Publication
 Petazzi , P, Torres, R, Fidanza, A, Roca-Ho, H, Gutierrez-Aguera, F, Diaz de la Guardia, R, Lopez-Millan, B, Bigas, A, Forrester, LM, Bueno, C, Menendez, P. (2019) ‘Robustness of dead Cas9 activators in human pluripotent and mesenchymal stem cells.’, Molecular Therapy Nucleic Acid - resubmitted revised version. doi: 10.1016/j.omtn.2020.02.009.View Publication
 Petazzi, P. et al. (2022) ‘Arterial cells support the development of human hematopoietic progenitors in vitro via secretion of IGFBP2’, bioRxiv. Cold Spring Harbor Laboratory, p. 2022.10.04.510611. doi: 10.1101/2022.10.04.510611.View Publication
 Petazzi, P. and Menendez, P. (2020) ‘A NEWral approach for HSC production in vitro?’, Blood. American Society of Hematology, 136(25), pp. 2845–2847. doi: 10.1182/blood.2020007864.View Publication
   

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