title: Engineering Hematopoietic Stem Cells: Lessons from Development.
abstract: Cell engineering has brought us tantalizingly close to the goal of deriving patient-specific hematopoietic stem cells (HSCs). While directed differentiation and transcription factor-mediated conversion strategies have generated progenitor cells with multilineage potential, to date, therapy-grade engineered HSCs remain elusive due to insufficient long-term self-renewal and inadequate differentiated progeny functionality. A cross-species approach involving zebrafish and mammalian systems offers complementary methodologies to improve understanding of native HSCs. Here, we discuss the role of conserved developmental timing processes in vertebrate hematopoiesis, highlighting how identification and manipulation of stage-specific factors that specify HSC developmental state must be harnessed to engineer HSCs for therapy.
authors.affiliation: Stem Cell Program and Division of Hematology/Oncology, Boston Children's Hospital, Boston, MA 02115, USA.
authors.forename: R Grant
authors.initials: RG
authors.lastname: Rowe
authors.affiliation: Stem Cell Program and Division of Hematology/Oncology, Boston Children's Hospital, Boston, MA 02115, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Mandelbaum
authors.affiliation: Stem Cell Program and Division of Hematology/Oncology, Boston Children's Hospital, Boston, MA 02115, USA; Howard Hughes Medical Institute, Boston, MA 02115, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA.
authors.forename: Leonard I
authors.initials: LI
authors.lastname: Zon
authors.affiliation: Stem Cell Program and Division of Hematology/Oncology, Boston Children's Hospital, Boston, MA 02115, USA; Howard Hughes Medical Institute, Boston, MA 02115, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA; Division of Hematology, Brigham and Women's Hospital, Boston, MA 02115, USA; Manton Center for Orphan Disease Research, Boston, MA 02115, USA. Electronic address: george.daley@childrens.harvard.edu.
authors.forename: George Q
authors.initials: GQ
authors.lastname: Daley
mesh_terms: D000818:Animals; D060846:Cell Engineering / Q000379:methods*; D047108:Embryonic Development; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans; D008954:Models, Biological; D013997:Time Factors