San Raffaele Telethon Institute for Gene Therapy
Human hematopoietic development and disease modeling
The Ditadi lab is a young and dynamic group that focuses on an ambitious and fundamental research program integrating developmental, cell and molecular biology. Our overarching research goal is to understand and recapitulate normal and pathological human hematopoietic development, both at the signaling and genetic level, with a particular interest in generating blood cell products to be used in the regenerative medicine framework. We harness the potential of human pluripotent stem cells (hPSC; comprising human embryonic stem cells - hESC - and induced pluripotent stem cells - hiPSC) to crack the code of the orchestrated network of pathways and factors that lead to the emergence of blood cells.
We are continuously looking to add dedicated and enthusiastic individuals at all career stages to our team. If you are interested in joining our group, we welcome applications and informal inquires contacting ditadi.andrea@hsr.it.
Research activity
Our research group focuses on the following two areas:
- Dynamic regulation of hematopoietic development: in this project, we aim at understanding the sequence of events that promotes the generation of blood cells, in particular hematopoietic stem cells and other therapeutically relevant blood cell types, such as lymphocytes and macrophages. Interestingly, during evolution the production of blood cells has been ‘outsourced’ to a different lineage, precisely to a subset of endothelial cells named hemogenic endothelial cells (HECs). As such, HSCs and all blood cells are generated via a process similar to a «lineage reprogramming». Using cutting-edge technologies applied to PSC and embryos as model systems, we investigate the molecular mechanisms regulating hematopoietic commitment, self-renewal and lineage specification in HECs.
- Ontogeny of blood disorders: Using iPSCs derived from patient affected by hematopoietic disorders, we want to identify the genetic requirements of specific critical stages of the development of the hematopoitic system and investigate the molecular mechanisms at the onset of these hematological diseases, representing the ultimate frontier of functional genetics. Collectively, our studies will provide new opportunities to study the genetic origins for blood disorders and to develop novel strategies for their treatment, including their application for cell therapy in the frame of regenerative medicine.
Luff SA, Creamer JP, Valsoni S, Dege C, Scarfò R, Dacunto A, Merelli I, Morris S, Ditadi A* and Sturgeon CM*. Identification of a retinoic acid-dependent hemogenic endothelial progenitor from human pluripotent stem cells. Nat Cell Biol 2022; 24(5):616-624
Atkins MH, Scarfò R, McGrath KE, Yang D, Palis J, Ditadi A and Keller GM. Modeling human yolk sac hematopoiesis with pluripotent stem cells. J Exp Med 2022;219(3):e20211924.
Portilho NA, Scarfò R, Bertesago E, Ismailoglu I, Kyba M, Kobayashi M, Ditadi A* and Yoshimoto M*. B-1 lymphocytes develop independently of Notch signaling during mouse embryonic development. Development 2021;48(15):dev199373. *co-last & co-corresponding author
Sugimura R, Jha DK, Han A, Soria-Valles C, da Rocha EL, Lu YF, Goettel JA, Serrao E, Rowe RG, Malleshaiah M, Wong I, Sousa P, Zhu TN, Ditadi A, Keller G, Engelman AN, Snapper SB, Doulatov S, Daley GQ. Haematopoietic stem and progenitor cells from human pluripotent stem cells. Nature 2017;545(7655):432-438.
Ditadi A, Sturgeon CM. Directed differentiation of definitive hemogenic endothelium and hematopoietic progenitors from human pluripotent stem cells. Methods 2015; S1046-2023(15)30119-5.
Ditadi A, Sturgeon CM, Tober J, Awong G, Kennedy M, Phillips A, Azzola L, Ng ES, Stanley E, French DL, Cheng X, Gadue P, Speck N, Elefanty AG, Keller G. Human definitive haemogenic endothelium and arterial vascular endothelium represent distinct lineages. Nat Cell Biol. 2015;17(5):580-91.
Sturgeon CM, Ditadi A, Awong G, Kennedy M, Keller G. Wnt signaling controls the specification of definitive and primitive hematopoiesis from human pluripotent stem cells. Nat Biotechnol. 2014;32(6):554-61.
Chanda B, Ditadi A, Iscove NN, Keller G. Retinoic acid signaling is essential for embryonic hematopoietic stem cell development. Cell 2013;155(1):215-27.
Sturgeon CM, Ditadi A, Clarke R, Keller G. Defining the path to hematopoietic stem cells. Nat Biotechnol. 2013; 31:416-18.
Kennedy M, Awong G, Sturgeon CM, Ditadi A, LaMotte-Mohs R, Zuniga- Pflucker JC, Keller G. T lymphocyte potential marks the emergence of definitive hematopoietic progenitors in human pluripotent stem cell differentiation cultures. Cell Rep. 2012; 27;2(6):1722-35.
Sturgeon CM, Chicha L, Ditadi A, Zhou Q, McGrath KE, Palis J, Hammond SM, Wang S, Olson EN, Keller G. Primitive erythropoiesis is regulated by miR-126 via nonhematopoietic Vcam-1(+) Cells. Dev Cell. 2012; 23(1):45-57.
Lagresle-Peyrou C, Six EM, Picard C, Rieux-Laucat F, Michel V, Ditadi A, Demerensde Chappedelaine C, Morillon E, Valensi F, Simon-Stoos KL, Mullikin JC, Noroski LM, Besse C, Wulffraat NM, Ferster A, Abecasis MM, Calvo F, Petit C, Candotti F, Abel L, Fischer A, Cavazzana-Calvo M. Human adenylate kinase 2 deficiency causes a profound hematopoietic defect associated with sensorineural deafness. Nat Genet. 2010; 41(1):106-11.
Ditadi A, de Coppi P, Picone O, Gautreau L, Smati R, Six E, Bonhomme D, Ezine S, Frydman R, Cavazzana-Calvo M, Andre-Schmutz I. Human and murine amniotic fluid c-Kit+Lin- cells display hematopoietic activity. Blood 2009; 113(17):3953-60.
