Pluripotent stem cells in embryo can self-renew and can generate all mature cell types in the body as their potency to self-renew progressively decreases. Adult organs possess populations of tissue-resident stem cells, which are capable of self-renewal to differentiate into all types of cells in the corresponding tissue. Tissue-resident stem cells can generate new stem cells through symmetric divisions (producing two similar stem cells) or asymmetric divisions (producing a stem cell and a non-stem cell) (Fig. 1). The resultant tissue-resident cells can be sustained by interacting with their microenvironment, niche, through activation of various signaling pathways, particularly Wnt/β-catenin, Hedghog, and Notch pathways. Simultaneously, non-stem cells lose self-renewal capacity and differentiate through a progenitor stage with a restricted differentiation capacity, to mature cell types, which are specific to their tissue of origin. Thus, tissue-resident stem cells are crucial for tissue homeostasis maintenance under both physiological and pathological conditions.

A seminal study reported the presence of a minor fraction of leukemia cells which can in vitro continue to proliferate similarly as hematopoietic stem cells (HSCs) can. In 1990’s, evidence is accumulating to indicate that these cells have a self-renewal capacity and can propagate leukemia upon their serial transplantation into animals. Based on these properties, they are named as leukemia-initiating cells or leukemia stem cells (LSCs). Subsequently, cell subpopulations with similar characteristics were detected in various kinds of solid cancers including breast, brain, colorectal, hepatocellular, and pancreatic cancers, and melanomas, and have been termed as cancer-initiating cells or cancer stem cells (CSCs). Like normal tissue-resident stem cells, LSCs and CSCs have a self-renewal ability to generate new stem cells through symmetric or asymmetric divisions. Self-renewal capacity of CSCs is maintained by the activation of several signaling pathways used by tissue-resident stem cells, such as Wnt/β-catenin, Hedgehog, or Notch pathway, in a cell context-dependent manner. CSCs are presumed to be crucially involved in various carcinogenesis steps, particularly malignant progression. In addition to CSCs, asymmetric divisions simultaneously generate cancer non-stem cell populations which compose most of cancer cells present in cancer tissues (Fig. 1), but the roles of cancer non-stem cells in carcinogenesis are often overlooked.

In this review, authors will briefly summarize biological aspects of CSCs and will discuss the potential roles of cancer non-stem cells in tumor microenvironment formation, by delineating the roles of non-stem cells in the pathogenesis of chronic myeloid leukemia (CML), a typical malignant disorder arising from LSCs.

Fig1. Hierarchy of stem and non-stem cells in normal and cancer tissues

Article Acess: https://link.springer.com/article/10.1186/s43556-021-00030-7

Website for Molecular: Biomedicine: https://www.springer.com/journal/43556

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