Unraveling the complex regulation of stem cells: implications for aging and cancer

Abstract

Substantial progress in embryonic and adult stem cell research in the past several years has yielded a wealth of information regarding the mechanisms regulating self-renewal and differentiation, two processes often used to define stem cells. Recent evidence suggests that epigenetic as well as genetic processes maintain stem cells in a pluripotent state as well as dictate their transition to more restricted stages of development. In this review, we discuss two emerging themes in stem cell biology, epigenetic control of gene expression and post-transcriptional regulation via microRNAs. We summarize how these regulatory mechanisms facilitate various aspects of normal stem cell biology and extend the discussion to their involvement in aging and tumorigeneisis, two biological phenomena intimately tied to stem cells. We speculate that aberrant epigenetic events and altered miRNA expression profiles in aged stem cell populations play important roles in carcinogenesis.

The bone marrow niche: habitat to hematopoietic and mesenchymal stem cells, and unwitting host to molecular parasites

“…The loss of microRNAs in aging of stem cells may promote tumorigenesis. 113 The role of bone marrow stromal cells in protecting leukemic cells from chemotherapy through cell-to-cell adhesion has been widely recognized. One possibility is that LSCs have much more active migration machinery when compared with HSCs that allow them to escape growth inhibition or quiescence promoting signals induced by osteoblasts and other stromal cells in the niche.…”

Very small embryonic-like (VSEL) stem cells in adult organs and their potential role in rejuvenation of tissues and longevity

“…This age-dependent content of VSELs in BM may explain why the regeneration processes are more efficient in younger individuals, when compared to older organisms. Further studies require the possibility that age-dependent decrease in number of pluripotent VSELs may be connected with age-related expansion of some tissue committed stem cells (TCSCs) -as seen in adult murine BM, where a number of monopotent hemato/lymphopoiesis committed HSC increase in older animals (Chambers andGoodell 2007, Oakley andvan Zant 2007).…”

Very small embryonic-like stem cells in adult tissues—Potential implications for aging

“…On the other hand, we hypothesize that since there is "a thin red line" between regeneration and tumor formation, it is likely that this population of very primitive stem cells may give rise to some types of cancer (e.g., pediatric sarcomas, teratomas, germinal tumors) when exposed to mutagenic environment (Buzzeo et al, 2007;Kucia et al, 2007d;Li et al, 2006;Liu et al, 2006;Oakley et al, 2007).…”