Concise review: Genetic dissection of hypoxia signaling pathways in normal and leukemic stem cells

Deniz Gezer, Milica Vukovic, Tomoyoshi Soga, Patrick J. Pollard, Kamil R. Kranc

研究成果: Review article査読

25 被引用数 (Scopus)

抄録

Adult hematopoiesis depends on rare multipotent hematopoietic stem cells (HSCs) that self-renew and give rise to progenitor cells, which differentiate to all blood lineages. The strict regulation of the fine balance between self-renewal and differentiation is essential for normal hematopoiesis and suppression of leukemia development. HSCs and progenitor cells are commonly assumed to reside within the hypoxic BM microenvironment, however, there is no direct evidence supporting this notion. Nevertheless, HSCs and progenitors do exhibit a hypoxic profile and strongly express Hif-1α. Although hypoxia signaling pathways are thought to play important roles in adult HSC maintenance and leukemogenesis, the precise function of Hif-dependent signaling in HSCs remains to be uncovered. Here we discuss recent gain-of-function and loss-of-function studies that shed light on the complex roles of hypoxia-signaling pathways in HSCs and their niches in normal and malignant hematopoiesis. Importantly, we comment on the current and often contrasting interpretations of the role of Hif-dependent signaling in stem cell functions. Stem Cells 2014;32:1390-1397

本文言語English
ページ(範囲)1390-1397
ページ数8
ジャーナルStem Cells
32
6
DOI
出版ステータスPublished - 2014 6月

ASJC Scopus subject areas

  • 分子医療
  • 発生生物学
  • 細胞生物学

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