title: Molecular landscapes of human hematopoietic stem cells in health and leukemia.
abstract: Blood cells are organized as a hierarchy with hematopoietic stem cells (HSCs) at the root. The advent of genomic technologies has opened the way for global characterization of the molecular landscape of HSCs and their progeny, both in mouse and human models, at the genetic, transcriptomic, epigenetic, and proteomics levels. Here, we outline our current understanding of the molecular programs that govern human HSCs and how dynamic changes occurring during HSC differentiation are necessary for well-regulated blood formation under homeostasis and upon injury. A large body of evidence is accumulating on how the programs of normal hematopoiesis are modified in acute myeloid leukemia, an aggressive adult malignancy driven by leukemic stem cells. We summarize these findings and their clinical implications.
authors.affiliation: Wellcome Trust - Medical Research Council Cambridge Stem Cell Institute, University of Cambridge, Cambridge, United Kingdom.|Department of Haematology, University of Cambridge, Cambridge, United Kingdom.|Paediatric Oncology, Royal Marsden Hospital, Sutton, London, United Kingdom.
authors.forename: Aditi
authors.initials: A
authors.lastname: Vedi
authors.affiliation: Wellcome Trust - Medical Research Council Cambridge Stem Cell Institute, University of Cambridge, Cambridge, United Kingdom.|Department of Haematology, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Antonella
authors.initials: A
authors.lastname: Santoro
authors.affiliation: Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
authors.forename: Cyrille F
authors.initials: CF
authors.lastname: Dunant
authors.affiliation: Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.|Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
authors.forename: John E
authors.initials: JE
authors.lastname: Dick
authors.affiliation: Wellcome Trust - Medical Research Council Cambridge Stem Cell Institute, University of Cambridge, Cambridge, United Kingdom.|Department of Haematology, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Elisa
authors.initials: E
authors.lastname: Laurenti
mesh_terms: D002454:Cell Differentiation / Q000502:physiology*; D006410:Hematopoiesis / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000378:metabolism / Q000473:pathology*; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D007938:Leukemia / Q000378:metabolism / Q000473:pathology*
keywords: acute myeloid leukemia; epigenetics; hematopoietic stem cells; transcriptomics