title: MicroRNA expression differences in human hematopoietic cell lineages enable regulated transgene expression.
abstract: Blood microRNA (miRNA) levels have been associated with and shown to participate in disease pathophysiology. However, the hematopoietic cell of origin of blood miRNAs and the individual blood cell miRNA profiles are poorly understood. We report the miRNA content of highly purified normal hematopoietic cells from the same individuals. Although T-cells, B-cells and granulocytes had the highest miRNA content per cell, erythrocytes contributed more cellular miRNA to the blood, followed by granulocytes and platelets. miRNA profiling revealed different patterns and different expression levels of miRNA specific for each lineage. miR-30c-5p was determined to be an appropriate reference normalizer for cross-cell qRT-PCR comparisons. miRNA profiling of 5 hematopoietic cell lines revealed differential expression of miR-125a-5p. We demonstrated endogenous levels of miR-125a-5p regulate reporter gene expression in Meg-01 and Jurkat cells by (1) constructs containing binding sites for miR-125a-5p or (2) over-expressing or inhibiting miR-125a-5p. This quantitative analysis of the miRNA profiles of peripheral blood cells identifies the circulating hematopoietic cellular miRNAs, supports the use of miRNA profiles for distinguishing different hematopoietic lineages and suggests that endogenously expressed miRNAs can be exploited to regulate transgene expression in a cell-specific manner.
authors.affiliation: Cardeza Foundation for Hematologic Research and Department of Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania, United States of America.
authors.forename: Raul
authors.initials: R
authors.lastname: Teruel-Montoya
authors.affiliation: Cardeza Foundation for Hematologic Research and Department of Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania, United States of America.
authors.forename: Xianguo
authors.initials: X
authors.lastname: Kong
authors.affiliation: Cardeza Foundation for Hematologic Research and Department of Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania, United States of America.
authors.forename: Shaji
authors.initials: S
authors.lastname: Abraham
authors.affiliation: Cardeza Foundation for Hematologic Research and Department of Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania, United States of America.
authors.forename: Lin
authors.initials: L
authors.lastname: Ma
authors.affiliation: Departments of Physiology, Pharmacology and Sol Sherry Thrombosis Research Center, Temple University School of Medicine, Philadelphia, Pennsylvania, United States of America.
authors.forename: Satya P
authors.initials: SP
authors.lastname: Kunapuli
authors.affiliation: Cardeza Foundation for Hematologic Research and Department of Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania, United States of America.
authors.forename: Michael
authors.initials: M
authors.lastname: Holinstat
authors.affiliation: Departments of Molecular and Human Genetics and Medicine, Baylor College of Medicine, Houston, Texas, United States of America; Department of Statistics, Rice University, Houston, Texas, United States of America.
authors.forename: Chad A
authors.initials: CA
authors.lastname: Shaw
authors.affiliation: Cardeza Foundation for Hematologic Research and Department of Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania, United States of America.
authors.forename: Steven E
authors.initials: SE
authors.lastname: McKenzie
authors.affiliation: Cardeza Foundation for Hematologic Research and Department of Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania, United States of America.
authors.forename: Leonard C
authors.initials: LC
authors.lastname: Edelstein
authors.affiliation: Cardeza Foundation for Hematologic Research and Department of Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania, United States of America.
authors.forename: Paul F
authors.initials: PF
authors.lastname: Bray
mesh_terms: D001773:Blood Cells / Q000166:cytology* / Q000378:metabolism*; D002460:Cell Line; D019070:Cell Lineage / Q000235:genetics*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006410:Hematopoiesis; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D019076:Transgenes / Q000235:genetics*
chemical_list: D035683:MicroRNAs