Establishment of a Normal Hematopoietic and Leukemia Stem Cell Hierarchy
ABSTRACT Many types of adult tissues, especially for high turnover tissues such as the blood and intestinal system, stand on a hierarchical tissue-specific stem cell system. Tissue-specific stem cells concurrently have self-renewal capacity and potential to give rise to all types of mature cells in their tissue. The differentiation process of the tissue-specific stem cell is successive restriction of these capacities. The first progeny of tissue-specific stem cells are multipotent progenitors (MPPs) that lose long-term self-renewal capacity yet have full lineage potential. MPPs in turn give rise to oligopotent progenitors, which then commit into lineage-restricted progenitors. This hierarchical system enables a lifelong supply of matured functional cells that generally have a short life span and a relatively high turnover rate. In this chapter, we review our findings and other key experiments that have led to the establishment of the current cellular stem and progenitor hierarchy in the blood-forming systems of mice and humans for both normal and leukemic hematopoiesis. We also review select signaling pathways intrinsic to normal hematopoietic and leukemic stem cell populations as well our recent findings elucidating the possible origin of the leukemia stem cell.
- SourceAvailable from: Annapoorni Rangarajan
- "Stem cell origin of cancer : Several tissues in our body present a hierarchical organization of cells ( Marshman et al . 2002 ; Chao et al . 2008 ; Makarem et al . 2013 ) – the tissue - resident adult stem cells divide and generate more of their own kind ( via self - renewal ) , and also generate committed cells ( progenitors ) that after few rounds of proliferation undergo terminal differentiation to give rise to the dif - ferentiated cells of the tissue ( figure 4a ) . Of these"
Article: Competing views on cancer[Show abstract] [Hide abstract]
ABSTRACT: Despite intense research efforts that have provided enormous insight, cancer continues to be a poorly understood disease. There has been much debate over whether the cancerous state can be said to originate in a single cell or whether it is a reflection of aberrant behaviour on the part of a 'society of cells'. This article presents, in the form of a debate conducted among the authors, three views of how the problem might be addressed. We do not claim that the views exhaust all possibilities. These views are (a) the tissue organization field theory (TOFT) that is based on a breakdown of tissue organization involving many cells from different embryological layers, (b) the cancer stem cell (CSC) hypothesis that focuses on genetic and epigenetic changes that take place within single cells, and (c) the proposition that rewiring of the cell's protein interaction networks mediated by intrinsically disordered proteins (IDPs) drives the tumorigenic process. The views are based on different philosophical approaches. In detail, they differ on some points and agree on others. It is left to the reader to decide whether one approach to understanding cancer appears more promising than the other.Journal of Biosciences 04/2014; 39(2):281-302. DOI:10.1007/s12038-013-9403-y · 1.94 Impact Factor
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- "Stem cells, as a broad terminology, reflect two distinct cell types: (1) embryonic stem cells (ESC), which are pluripotent, having the ability to both self renew indefinitely and differentiate into cells of all 3 germ layers (endoderm, ectoderm and mesoderm); and (2) adult stem cells, which have differentiated but retain some capacity to self-renewal and are more restricted in their potential to differentiate. For example, some adult stem cells (or tissue specific stem cells) are capable of giving rise to several specialized cell types (multipotent stem cells) while others are limited to a single specialized cell type (unipotent stem cell). The descendants of stem cells and representing the next level of differentiation are progenitor cells. "
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- "New cell types have been added to represent hematopoietic progenitor cell types that are currently an intense focus of research (Figure 2b). For Hemo_CL, progenitor cell classes are organized under multipotent progenitor, oligopotent progenitor, and lineage restricted progenitor cell types in a commonly used schema . Multipotent progenitors develop from stem cells and have the ability to develop into any hematopoietic cell type but have limited self-renewal capability. "
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