Human hematopoietic development and disease modeling
The Human hematopoietic development and disease modeling Unit is a young and dynamic group that focuses on an ambitious and fundamental research program integrating developmental cell and molecular biology. The 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.
- The group will model hematopoietic development to understand the sequence of events that promotes the generation of hematopoietic stem cells. Researchers will investigate the molecular mechanisms regulating human hematopoietic commitment and lineage specification using hPSC as well as mouse PSCs and embryos as model systems.
- The group will exploit hiPSCs derived from patient affected by hematopoietic disorders to identify the genetic requirements of specific critical stages of the development of the immune system and investigate the molecular mechanisms at the onset of these hematological diseases, representing the ultimate frontier of functional genetics.
Ditadi A, Sturgeon CM, Keller G. A view of human hematopoietic development from the Petri dish. Nat Rev Mol Cell Biol. 2017; 18(1):56-67.
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.