title: Hematopoietic progenitor cell lines with myeloid and lymphoid potential.
abstract: Investigation of immune-cell differentiation and function is limited by shortcomings of suitable and scalable experimental systems. Here we show that retroviral delivery of an estrogen-regulated form of Hoxb8 into mouse bone marrow cells can be used along with Flt3 ligand to conditionally immortalize early hematopoietic progenitor cells (Hoxb8-FL cells). Hoxb8-FL cells have lost self-renewal capacity and potential to differentiate into megakaryocytes and erythrocytes but retain the potential to differentiate into myeloid and lymphoid cells. They differentiate in vitro and in vivo into macrophages, granulocytes, dendritic cells, B lymphocytes and T lymphocytes that are phenotypically and functionally indistinguishable from their primary counterparts. Quantitative in vitro assays indicate that myeloid and B-cell potential of Hoxb8-FL cells is comparable to that of primary lymphoid-primed multipotent progenitors, whereas T-cell potential is diminished. The simplicity of this system and the unlimited proliferative capacity of Hoxb8-FL cells will enable studies of immune-cell differentiation and function.
authors.affiliation: Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Redecke
authors.forename: Ruiqiong
authors.initials: R
authors.lastname: Wu
authors.forename: Jingran
authors.initials: J
authors.lastname: Zhou
authors.forename: David
authors.initials: D
authors.lastname: Finkelstein
authors.forename: Vandana
authors.initials: V
authors.lastname: Chaturvedi
authors.forename: Anthony A
authors.initials: AA
authors.lastname: High
authors.forename: Hans
authors.initials: H
authors.lastname: Häcker
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology*; D002454:Cell Differentiation / Q000502:physiology; D019070:Cell Lineage; D005260:Female; D005434:Flow Cytometry; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D018398:Homeodomain Proteins / Q000378:metabolism*; D008214:Lymphocytes / Q000166:cytology* / Q000648:ultrastructure; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D022423:Myeloid Cells / Q000166:cytology* / Q000648:ultrastructure; D025341:Principal Component Analysis; D040901:Proteomics
chemical_list: C490669:HOXB8 protein, human; D018398:Homeodomain Proteins; D008565:Membrane Proteins; C084881:flt3 ligand protein