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Author Notes:

Correspondence to: Kevin D. Bunting, email: Kevin.bunting@emory.edu

Z. Wang planned experiments, performed experiments, analyzed data, and wrote the manuscript.

K. Bunting planned experiments, analyzed data, and wrote the manuscript.

We received expert advice from the Emory Biostatistics and Bioinformatics shared resource and biostatistical assistance from Dr. Fang Xu (Centers for Disease Control).

We also acknowledge the Emory + Children's Pediatrics flow cytometry core facility and the Genome Analysis Core Facility at Georgia Tech, Parker H. Petit Institute for Bioengineering and Bioscience.

The authors declare no conflicts of interest

Subjects:

Research Funding:

We acknowledge our funding sources which include R01DK059380, the Cure Childhood Cancer Foundation, and the Aflac Cancer and Blood Disorders Center of Children's Healthcare of Atlanta and Emory University.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Oncology
  • Cell Biology
  • hematopoiesis
  • transcription factor
  • single-cell gene expression analysis
  • transcriptional heterogeneity
  • leukemogenesis
  • CLONAL HEMATOPOIESIS
  • CELL-PROLIFERATION
  • STEM-CELLS
  • LEUKEMOGENESIS
  • PROGENITORS
  • DIFFERENTIATION
  • LEUKEMIA

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

Tools:

Journal Title:

Oncotarget

Volume:

Volume 8, Number 14

Publisher:

, Pages 22477-22482

Type of Work:

Article | Final Publisher PDF

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 wildtype 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.

Copyright information:

© 2017 Wang and Bunting

This is an Open Access work distributed under the terms of the Creative Commons Attribution 3.0 Unported License (http://creativecommons.org/licenses/by/3.0/).

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