title: Stat5 deficiency decreases transcriptional heterogeneity and supports emergence of hematopoietic sub-populations.
abstract: Aging is associated with significant changes in hematopoiesis, including clonal dominance, anemia, myeloid malignancies, and reduced activation of signal transducer and activator of transcription 5 (Stat5). In previous studies, Stat5 deletion surprisingly amplified FLT3/ITD+ myeloid expansion or Myc-driven lymphoid expansion. Here we show that Stat5 deficiency has a strong impact upon transcriptional heterogeneity in single sorted c-Kit+Lin-Sca-1+ (KLS) cells or CD150+CD48- KLS long-term repopulating hematopoietic stem cells (LT-HSC). Single cell polymerase chain reaction (PCR) was performed on selected regulators of multi-lineage hematopoiesis. At least two dominant sub-populations were identified by increased expression of cell cycle regulatory and leukemia-associated genes. Furthermore, in the top expressing quartile of cells, the majority of genes were proportionally overrepresented. In wild-type KLS cells, Stat5 mRNA levels were also strongly correlated with several genes. Since heterogeneity decreases with age or inflammatory or oncogenic stress, these results provide a potential mechanistic linkage to Stat5 expression.
authors.affiliation: Department of Pediatrics, Aflac Cancer and Blood Disorders Center of Children's Healthcare of Atlanta and Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Zhengqi
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Pediatrics, Aflac Cancer and Blood Disorders Center of Children's Healthcare of Atlanta and Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Kevin D
authors.initials: KD
authors.lastname: Bunting
mesh_terms: D000818:Animals; D019070:Cell Lineage / Q000235:genetics*; D002478:Cells, Cultured; D004622:Embryo, Mammalian; D018740:Genetic Heterogeneity; D006410:Hematopoiesis / Q000235:genetics*; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D050799:STAT5 Transcription Factor / Q000235:genetics*; D014158:Transcription, Genetic / Q000235:genetics*
chemical_list: D050799:STAT5 Transcription Factor
keywords: hematopoiesis; leukemogenesis; single-cell gene expression analysis; transcription factor; transcriptional heterogeneity