title: Brief report: ectopic expression of NUP98-HOXA10 augments erythroid differentiation of human embryonic stem cells.
abstract: Hox genes encode highly conserved transcription factors that have been implicated in hematopoietic development and self-renewal of hematopoietic stem cells (HSCs) and hematopoietic development. The potency of NUP98-HOXA10hd (NA10) on adult murine bone marrow HSC self-renewal prompted us to examine its effect on specification and proliferation of hematopoietic cells derived from human embryonic stem cells (hESCs). Here, we demonstrate that expression of NA10 in hESCs influences the hematopoietic differentiation program. The specific effect of NA10 is dependent on the developmental stage of hematopoietic emergence from hESCs. Overexpression of NA10 in either undifferentiated hESCs or early hemogenic precursors augmented the frequency of CD45(-) GlycophorinA(+) cells and erythroid progenitors (blast-forming unit-erythrocyte). In contrast, targeted NA10 expression in primitive CD34+ cells committed to the hematopoietic lineage had no effect on erythropoietic capacity but instead increased hematopoietic progenitor proliferation. Our study reveals a novel neomorphic effect of NA10 in early human erythroid development from pluripotent stem cells.
authors.affiliation: Stem Cell and Cancer Research Institute, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Junfeng
authors.initials: J
authors.lastname: Ji
authors.forename: Ruth M
authors.initials: RM
authors.lastname: Risueño
authors.forename: Seokho
authors.initials: S
authors.lastname: Hong
authors.forename: David
authors.initials: D
authors.lastname: Allan
authors.forename: Patty
authors.initials: P
authors.lastname: Rosten
authors.forename: Keith
authors.initials: K
authors.lastname: Humphries
authors.forename: Mickie
authors.initials: M
authors.lastname: Bhatia
mesh_terms: D018952:Antigens, CD34; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D041905:Erythroid Cells / Q000166:cytology / Q000378:metabolism*; D004920:Erythropoiesis; D005434:Flow Cytometry; D015870:Gene Expression; D006021:Glycophorins / Q000096:biosynthesis; D000080905:Homeobox A10 Proteins; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D017493:Leukocyte Common Antigens / Q000096:biosynthesis; D028861:Nuclear Pore Complex Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D018952:Antigens, CD34; D006021:Glycophorins; D000080905:Homeobox A10 Proteins; D018398:Homeodomain Proteins; D028861:Nuclear Pore Complex Proteins; C465451:Nup98 protein, human; C069634:HOXA10 protein, human; D017493:Leukocyte Common Antigens