Defining a stem cell hierarchy in the intestine: markers, caveats and controversies
TLDR
New and potentially paradigm‐shifting discoveries within the intestinal epithelium are intriguing, but the field will require development of a number of critical tools, including highly specific stem cell marker genes along with more rigorous experimental methodologies, to delineate the complex cellular relationships within this dynamic organ system.Abstract:
The past decade has appreciated rapid advance in identifying the once elusive intestinal stem cell (ISC) populations that fuel the continual renewal of the epithelial layer. This advance was largely driven by identification of novel stem cell marker genes, revealing the existence of quiescent, slowly- and active-cycling ISC populations. However, a critical barrier for translating this knowledge to human health and disease remains elucidating the functional interplay between diverse stem cell populations. Currently, the precise hierarchical and regulatory relationships between these ISC populations are under intense scrutiny. The classical theory of a linear hierarchy, where quiescent and slowly-cycling stem cells self-renew but replenish an active-cycling population, is well established in other rapidly renewing tissues such as the haematopoietic system. Efforts to definitively establish a similar stem cell hierarchy within the intestinal epithelium have yielded conflicting results, been difficult to interpret, and suggest non-conventional alternatives to a linear hierarchy. While these new and potentially paradigm-shifting discoveries are intriguing, the field will require development of a number of critical tools, including highly specific stem cell marker genes along with more rigorous experimental methodologies, to delineate the complex cellular relationships within this dynamic organ system.read more
Citations
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Advancing Intestinal Organoid Technology Toward Regenerative Medicine
Tetsuya Nakamura,Toshiro Sato +1 more
TL;DR: There is growing interest in using cultured intestinal cells in vitro as a source for tissue engineering and regenerative medicine for intestinal diseases in humans to urge them to mature into functional intestines by implanting them into hosts.
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Single cell analysis of Crohn's disease patient-derived small intestinal organoids reveals disease activity-dependent modification of stem cell properties
Kohei Suzuki,Tatsuro Murano,Hiromichi Shimizu,Go Ito,Toru Nakata,Satoru Fujii,Fumiaki Ishibashi,Ami Kawamoto,Sho Anzai,Reiko Kuno,Konomi Kuwabara,Junichi Takahashi,Minami Hama,Sayaka Nagata,Yui Hiraguri,Kento Takenaka,Shiro Yui,Kiichiro Tsuchiya,Tetsuya Nakamura,Kazuo Ohtsuka,Mamoru Watanabe,Ryuichi Okamoto +21 more
TL;DR: Results suggest modification of small intestinal stem cell properties by unidentified factors in the inflammatory environment of Crohn’s disease with high organoid reformation ability.
Journal ArticleDOI
Ageing, metabolism and the intestine
TL;DR: Current insights gained from model organisms indicate how changes in metabolic signalling during ageing are a major driver for the loss of stem cell plasticity and epithelial homeostasis, ultimately affecting the resilience of an organism and limiting its lifespan.
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Plasticity of differentiated cells in wound repair and tumorigenesis, part II: skin and intestine.
Joseph Burclaff,Jason C. Mills +1 more
TL;DR: This final installment of a two-part Review discusses how cycles of dedifferentiation and redifferentiation can promote tumorigenesis in the skin and intestine, showing how plasticity in these continuously renewing tissues might contribute to tumors.
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Intestinal renewal across the animal kingdom: comparing stem cell activity in mouse and Drosophila.
TL;DR: This review focuses on recent advances in understanding of ISC identity, behavior, and regulation during homeostasis and injury-induced repair, as revealed by two major animal models used to study regeneration of the small intestine: Drosophila melanogaster and Mus musculus.
References
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