title: Generation of hematopoietic repopulating cells from human embryonic stem cells independent of ectopic HOXB4 expression.
abstract: Despite the need for alternative sources of human hematopoietic stem cells (HSCs), the functional capacity of hematopoietic cells generated from human embryonic stem cells (hESCs) has yet to be evaluated and compared with adult sources. Here, we report that somatic and hESC-derived hematopoietic cells have similar phenotype and in vitro clonogenic progenitor activity. However, in contrast with somatic cells, hESC-derived hematopoietic cells failed to reconstitute intravenously transplanted recipient mice because of cellular aggregation causing fatal emboli formation. Direct femoral injection allowed recipient survival and resulted in multilineage hematopoietic repopulation, providing direct evidence of HSC function. However, hESC-derived HSCs had limited proliferative and migratory capacity compared with somatic HSCs that correlated with a distinct gene expression pattern of hESC-derived hematopoietic cells that included homeobox (HOX) A and B gene clusters. Ectopic expression of HOXB4 had no effect on repopulating capacity of hESC-derived cells. We suggest that limitations in the ability of hESC-derived HSCs to activate a molecular program similar to somatic HSCs may contribute to their atypical in vivo behavior. Our study demonstrates that HSCs can be derived from hESCs and provides an in vivo system and molecular foundation to evaluate strategies for the generation of clinically transplantable HSC from hESC lines.
authors.affiliation: Robarts Research Institute, Krembil Center for Stem Cell Biology and Regenerative Medicine, Ontario, Canada.
authors.forename: Lisheng
authors.initials: L
authors.lastname: Wang
authors.forename: Pablo
authors.initials: P
authors.lastname: Menendez
authors.forename: Farbod
authors.initials: F
authors.lastname: Shojaei
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Frederick
authors.initials: F
authors.lastname: Mazurier
authors.forename: John E
authors.initials: JE
authors.lastname: Dick
authors.forename: Chantal
authors.initials: C
authors.lastname: Cerdan
authors.forename: Krysta
authors.initials: K
authors.lastname: Levac
authors.forename: Mickie
authors.initials: M
authors.lastname: Bhatia
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D019070:Cell Lineage / Q000502:physiology*; D002478:Cells, Cultured; D004622:Embryo, Mammalian / Q000166:cytology / Q000502:physiology; D005786:Gene Expression Regulation / Q000502:physiology; D006410:Hematopoiesis / Q000502:physiology; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000502:physiology; D018398:Homeodomain Proteins / Q000096:biosynthesis; D006801:Humans; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology* / Q000502:physiology; D014157:Transcription Factors
chemical_list: C090460:HOXB4 protein, human; D018398:Homeodomain Proteins; C513262:Hoxb4 protein, mouse; D014157:Transcription Factors