Stat5 deficiency decreases transcriptional heterogeneity and supports emergence of hematopoietic sub-populations

• Published in: Oncotarget Vol. 8; no. 14; pp. 22477 - 22482
• Main Authors: Wang, Zhengqi, Bunting, Kevin D
• Format: Journal Article
• Language: English
• Published: United States Impact Journals LLC 04.04.2017
• Subjects: Animals; Cell Lineage - genetics; Cells, Cultured; Embryo, Mammalian; Genetic Heterogeneity; Hematopoiesis - genetics; Hematopoietic Stem Cells - physiology; Mice; Mice, Transgenic; Research Paper; STAT5 Transcription Factor - genetics; Transcription, Genetic - genetics; single-cell gene expression analysis; transcription factor; hematopoiesis; leukemogenesis; transcriptional heterogeneity
• ISSN: 1949-2553; 1949-2553
• DOI: 10.18632/oncotarget.15236

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.