Abstract
Hematopoietic stem cells (HSCs) that give rise to all kinds of hematopoietic lineage cells on various demands throughout life are maintained in a specialized microenvironment called “niche” in the bone marrow (BM). Defining niche cells and unveiling its function have been the subject of intense study, and it is becoming increasingly clear how niche cells regulate HSCs in normal hematopoiesis. Leukemia stem cells (LSCs), which are able to produce leukemic cells and maintain leukemic clones, are assumed to share common features with healthy HSCs. Accumulating evidence suggests that LSCs reside in a specialized BM microenvironment; moreover, LSCs could control and rebuild the microenvironment to enhance their progression and survival. This article discusses the recent advances in our knowledge of the microenvironment supporting malignant hematopoiesis, including LSC niche.
Highlights
Hematopoiesis needs to be maintained throughout life to supply blood cells on various demands, such as infection, inflammation, blood loss, or hypoxia
The depletion of osteocytes using transgenic mice in which diphtheria toxin receptor was expressed under the control of dentin matrix protein-1 (Dmp-1) promoter led to a suppression of osteoblasts, resulting in a defect of hematopoietic stem/progenitor cell (HSPC) mobilization by granulocyte-colony-stimulating factor (G-CSF)
These cells include CXCL12-abundant reticular (CAR) cells [28,29,30], which are cells marked by green fluorescent protein (GFP) under the elements of the nestin promoter (Nes-GFP+) [31], leptin receptor (LepR)-expressing cells [16, 17], CD144−CD146−Sca-1+ mesenchymal stromal progenitors [32], and the stromal cells targeted by Cre recombinase promoted by transcription factor osterix (Osx) [18], neural/glial antigen 2 (NG2) [33], or paired related homeobox-1 [17, 18]
Summary
Hematopoietic stem cells (HSCs) that give rise to all kinds of hematopoietic lineage cells on various demands throughout life are maintained in a specialized microenvironment called “niche” in the bone marrow (BM). Defining niche cells and unveiling its function have been the subject of intense study, and it is becoming increasingly clear how niche cells regulate HSCs in normal hematopoiesis. Leukemia stem cells (LSCs), which are able to produce leukemic cells and maintain leukemic clones, are assumed to share common features with healthy HSCs. Accumulating evidence suggests that LSCs reside in a specialized BM microenvironment; LSCs could control and rebuild the microenvironment to enhance their progression and survival. This article discusses the recent advances in our knowledge of the microenvironment supporting malignant hematopoiesis, including LSC niche
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