Ernst Laboratory - Runx1 Loss Minimally Impacts Long-Term

Journal article

Xiongwei Cai, J. Gaudet, J. Mangan, Michael J. Chen, M. D. De Obaldia, Z. Oo, P. Ernst, N. Speck
PLoS ONE, 2011

Semantic Scholar DOI PubMedCentral PubMed

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APA Click to copy
Cai, X., Gaudet, J., Mangan, J., Chen, M. J., Obaldia, M. D. D., Oo, Z., … Speck, N. (2011). Runx1 Loss Minimally Impacts Long-Term Hematopoietic Stem Cells. PLoS ONE.

Chicago/Turabian Click to copy
Cai, Xiongwei, J. Gaudet, J. Mangan, Michael J. Chen, M. D. De Obaldia, Z. Oo, P. Ernst, and N. Speck. “Runx1 Loss Minimally Impacts Long-Term Hematopoietic Stem Cells.” PLoS ONE (2011).

MLA Click to copy
Cai, Xiongwei, et al. “Runx1 Loss Minimally Impacts Long-Term Hematopoietic Stem Cells.” PLoS ONE, 2011.

BibTeX Click to copy

@article{xiongwei2011a,
  title = {Runx1 Loss Minimally Impacts Long-Term Hematopoietic Stem Cells},
  year = {2011},
  journal = {PLoS ONE},
  author = {Cai, Xiongwei and Gaudet, J. and Mangan, J. and Chen, Michael J. and Obaldia, M. D. De and Oo, Z. and Ernst, P. and Speck, N.}
}

Abstract

RUNX1 encodes a DNA binding subunit of the core-binding transcription factors and is frequently mutated in acute leukemia, therapy-related leukemia, myelodysplastic syndrome, and chronic myelomonocytic leukemia. Mutations in RUNX1 are thought to confer upon hematopoietic stem cells (HSCs) a pre-leukemic state, but the fundamental properties of Runx1 deficient pre-leukemic HSCs are not well defined. Here we show that Runx1 deficiency decreases both apoptosis and proliferation, but only minimally impacts the frequency of long term repopulating HSCs (LT-HSCs). It has been variously reported that Runx1 loss increases LT-HSC numbers, decreases LT-HSC numbers, or causes age-related HSC exhaustion. We attempt to resolve these discrepancies by showing that Runx1 deficiency alters the expression of several key HSC markers, and that the number of functional LT-HSCs varies depending on the criteria used to score them. Finally, we identify genes and pathways, including the cell cycle and p53 pathways that are dysregulated in Runx1 deficient HSCs.