Activation of CCAAT/Enhancer-Binding Protein alpha or PU.1 in Hematopoietic Stem Cells Leads to Their Reduced Self-Renewal and Proliferation

作者：Fukuchi Yumi; Ito Miyuki; Shibata Fumi; Kitamura Toshio; Nakajima Hideaki^*

来源：Stem Cells, 2008, 26(12): 3172-3181.

DOI：10.1634/stemcells.2008-0320

• Hematopoietic stem cell
• CCAAT/enhancer-binding protein alpha
• PU.1
• Self-renewal

Previous studies using loss-of-function mutants revealed that CCAAT/enhancer-binding protein alpha (C/EBP alpha) and PU.1 are potential regulators for hematopoietic stem cells (HSCs). To gain further insight into the HSC regulation by C/EBP alpha or PU.1, we used transgenic mice expressing conditional forms of these transcription factors to examine whether their activation alone is sufficient for modulating HSC functions. The activation of C/EBP alpha or PU.1 in HSCs in vitro or in vivo led to their suppression of growth, decreased mixed colony formation, and impaired competitive repopulating activities because of their defective self-renewal. These effects were more prominently observed when C/EBP alpha was activated, and the differentiation capacity to megakaryocytic lineage was selectively impaired upon C/EBP alpha activation. Unexpectedly, the expression of Bmi-1 and HoxB4, well-known regulators for self-renewal of HSCs, was not affected by the activation of C/EBP alpha or PU.1, suggesting that they regulate HSC function through an as yet unknown mechanism. Our data suggest that the activation of C/EBP alpha or PU.1 is sufficient to repress stem cell capacities in HSCs, and their fine-tuned regulation is critical for HSC homeostasis. STEM CELLS 2008;26:3172-3181

• 出版日期2008
• 单位河北医科大学