Mo1835 Investigation of Slow Cycling Stem Cells and Paneth Cells in T. Spiralis-Induced Small Intestinal Inflammation

Stem cells have been identified in two locations in small intestinal crypts; those intercalated between Paneth cells and another population (which retains DNA label) are located above the Paneth cell zone, at cell position 4. Because of disadvantages associated with the use of DNA label, doxycycline-induced transient transgenic expression of histone 2B (H2B)-green fluorescent protein (GFP) was investigated. H2B-GFP-retaining putative stem cells were consistently seen, with a peak at cell position 4, over chase periods of up to 112 days. After a 28-day chase, a subpopulation of the H2B-GFP-retaining cells was cycling, but the slow cycling status of the majority was illustrated by lack of expression of pHistone H3 and Ki67. Although some H2B-GFP-retaining cells were sensitive to low-dose radiation, the majority was resistant to low- and high-dose radiation-induced cell death, and a proportion of the surviving cells proliferated during subsequent epithelial regeneration. Long-term retention of H2B-GFP in a subpopulation of small intestinal Paneth cells was also seen, implying that they are long lived. In contrast to the small intestine, H2B-GFP-retaining epithelial cells were not seen in the colon from 28-day chase onward. This implies important differences in stem cell function between these two regions of the gastrointestinal tract, which may have implications for region-specific susceptibility to diseases (such as cancer and ulcerative colitis), in which epithelial stem cells and their progeny are involved.

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Nutrient sensing by absorptive and secretory progenies of small intestinal stem cells

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00416.2016 ◽

2017 ◽

Vol 312 (6) ◽

pp. G592-G605 ◽

Cited By ~ 13

Author(s):

Kunihiro Kishida ◽

Sarah C. Pearce ◽

Shiyan Yu ◽

Nan Gao ◽

Ronaldo P. Ferraris

Keyword(s):

Stem Cells ◽

Cell Types ◽

Paneth Cells ◽

Nutrient Sensing ◽

Intestinal Stem Cells ◽

Intestinal Cell ◽

Cell Type ◽

Extended Lifespan ◽

Small Intestinal ◽

Single Cell Type

Nutrient sensing triggers responses by the gut-brain axis modulating hormone release, feeding behavior and metabolism that become dysregulated in metabolic syndrome and some cancers. Except for absorptive enterocytes and secretory enteroendocrine cells, the ability of many intestinal cell types to sense nutrients is still unknown; hence we hypothesized that progenitor stem cells (intestinal stem cells, ISC) possess nutrient sensing ability inherited by progenies during differentiation. We directed via modulators of Wnt and Notch signaling differentiation of precursor mouse intestinal crypts into specialized organoids each containing ISC, enterocyte, goblet, or Paneth cells at relative proportions much higher than in situ as determined by mRNA expression and immunocytochemistry of cell type biomarkers. We identified nutrient sensing cell type(s) by increased expression of fructolytic genes in response to a fructose challenge. Organoids comprised primarily of enterocytes, Paneth, or goblet, but not ISC, cells responded specifically to fructose without affecting nonfructolytic genes. Sensing was independent of Wnt and Notch modulators and of glucose concentrations in the medium but required fructose absorption and metabolism. More mature enterocyte- and goblet-enriched organoids exhibited stronger fructose responses. Remarkably, enterocyte organoids, upon forced dedifferentiation to reacquire ISC characteristics, exhibited a markedly extended lifespan and retained fructose sensing ability, mimicking responses of some dedifferentiated cancer cells. Using an innovative approach, we discovered that nutrient sensing is likely repressed in progenitor ISCs then irreversibly derepressed during specification into sensing-competent absorptive or secretory lineages, the surprising capacity of Paneth and goblet cells to detect fructose, and the important role of differentiation in modulating nutrient sensing. NEW & NOTEWORTHY Small intestinal stem cells differentiate into several cell types transiently populating the villi. We used specialized organoid cultures each comprised of a single cell type to demonstrate that 1) differentiation seems required for nutrient sensing, 2) secretory goblet and Paneth cells along with enterocytes sense fructose, suggesting that sensing is acquired after differentiation is triggered but before divergence between absorptive and secretory lineages, and 3) forcibly dedifferentiated enterocytes exhibit fructose sensing and lifespan extension.

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Paneth cells mediated the response of intestinal stem cells at the early stage of intestinal inflammation in the chicken

Poultry Science ◽

10.1016/j.psj.2020.11.055 ◽

2020 ◽

Author(s):

Lingzi Yu ◽

Xiaochen Xie ◽

Keyang Jiang ◽

Yi Hong ◽

Zhou Zhou ◽

...

Keyword(s):

Stem Cells ◽

Intestinal Inflammation ◽

Early Stage ◽

Paneth Cells ◽

Intestinal Stem Cells

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The Potential of Nail Mini-Organ Stem Cells in Skin, Nail and Digit Tips Regeneration

International Journal of Molecular Sciences ◽

10.3390/ijms22062864 ◽

2021 ◽

Vol 22 (6) ◽

pp. 2864

Author(s):

Anna Pulawska-Czub ◽

Tomasz D. Pieczonka ◽

Paula Mazurek ◽

Krzysztof Kobielak

Keyword(s):

Stem Cells ◽

Critical Role ◽

Nail Plate ◽

Molecular Characteristics ◽

Continuous Growth ◽

Physiological Conditions ◽

Morphogenetic Protein ◽

Slow Cycling ◽

Bifunctional Properties

Nails are highly keratinized skin appendages that exhibit continuous growth under physiological conditions and full regeneration upon removal. These mini-organs are maintained by two autonomous populations of skin stem cells. The fast-cycling, highly proliferative stem cells of the nail matrix (nail stem cells (NSCs)) predominantly replenish the nail plate. Furthermore, the slow-cycling population of the nail proximal fold (nail proximal fold stem cells (NPFSCs)) displays bifunctional properties by contributing to the peri-nail epidermis under the normal homeostasis and the nail structure upon injury. Here, we discuss nail mini-organ stem cells’ location and their role in skin and nail homeostasis and regeneration, emphasizing their importance to orchestrate the whole digit tip regeneration. Such endogenous regeneration capabilities are observed in rodents and primates. However, they are limited to the region adjacent to the nail’s proximal area, indicating the crucial role of nail mini-organ stem cells in digit restoration. Further, we explore the molecular characteristics of nail mini-organ stem cells and the critical role of the bone morphogenetic protein (BMP) and Wnt signaling pathways in homeostatic nail growth and digit restoration. Finally, we investigate the latest accomplishments in stimulating regenerative responses in regeneration-incompetent injuries. These pioneer results might open up new opportunities to overcome amputated mammalian digits and limbs’ regenerative failures in the future.

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A novel in vitro survival assay of small intestinal stem cells after exposure to ionizing radiation

Journal of Radiation Research ◽

10.1093/jrr/rrt123 ◽

2014 ◽

Vol 55 (2) ◽

pp. 381-390 ◽

Cited By ~ 11

Author(s):

Motohiro Yamauchi ◽

Kensuke Otsuka ◽

Hisayoshi Kondo ◽

Nobuyuki Hamada ◽

Masanori Tomita ◽

...

Keyword(s):

Stem Cells ◽

Ionizing Radiation ◽

Intestinal Stem Cells ◽

Survival Assay ◽

Small Intestinal ◽

In Vitro Survival

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Small-Intestinal Bacterial Overgrowth is Associated With Concurrent Intestinal Inflammation But Not With Systemic Inflammation in Crohn’s Disease Patients

Journal of Clinical Gastroenterology ◽

10.1097/mcg.0000000000000803 ◽

2018 ◽

Vol 52 (6) ◽

pp. 530-536 ◽

Cited By ~ 11

Author(s):

José E.R. Ricci ◽

Liliana A. Chebli ◽

Tarsila C.d.R. Ribeiro ◽

Antonio C.S. Castro ◽

Pedro D. Gaburri ◽

...

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Systemic Inflammation ◽

Intestinal Inflammation ◽

Bacterial Overgrowth ◽

Small Intestinal Bacterial Overgrowth ◽

Intestinal Bacterial Overgrowth ◽

Small Intestinal

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Acute small intestinal inflammation results in persistent lymphatic alterations

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00340.2017 ◽

2018 ◽

Vol 314 (3) ◽

pp. G408-G417 ◽

Cited By ~ 6

Author(s):

Sonia Rehal ◽

Matthew Stephens ◽

Simon Roizes ◽

Shan Liao ◽

Pierre-Yves von der Weid

Keyword(s):

Dendritic Cell ◽

Lymphatic System ◽

Intestinal Inflammation ◽

Critical Role ◽

Lymphatic Vessels ◽

Lymphoid Tissues ◽

Functional Changes ◽

Increased Risk ◽

Small Intestinal ◽

Acute Ileitis

Inflammatory bowel disease (IBD) has a complex pathophysiology with limited treatments. Structural and functional changes in the intestinal lymphatic system have been associated with the disease, with increased risk of IBD occurrence linked to a history of acute intestinal injury. To examine the potential role of the lymphatic system in inflammation recurrence, we evaluated morphological and functional changes in mouse mucosal and mesenteric lymphatic vessels, and within the mesenteric lymph nodes during acute ileitis caused by a 7-day treatment with dextran sodium sulfate (DSS). We monitored whether the changes persisted during a 14-day recovery period and determined their potential consequences on dendritic cell (DC) trafficking between the mucosa and lymphoid tissues. DSS administration was associated with marked lymphatic abnormalities and dysfunctions exemplified by lymphangiectasia and lymphangiogenesis in the ileal mucosa and mesentery, increased mesenteric lymphatic vessel leakage, and lymphadenopathy. Lymphangiogenesis and lymphadenopathy were still evident after recovery from intestinal inflammation and correlated with higher numbers of DCs in mucosal and lymphatic tissues. Specifically, a deficit in CD103+ DCs observed during acute DSS in the lamina propria was reversed and further enhanced during recovery. We concluded that an acute intestinal insult caused alterations of the mesenteric lymphatic system, including lymphangiogenesis, which persisted after resolution of inflammation. These morphological and functional changes could compromise DC function and movement, increasing susceptibility to further gastrointestinal disease. Elucidation of the changes in mesenteric and intestinal lymphatic function should offer key insights for new therapeutic strategies in gastrointestinal disorders such as IBD. NEW & NOTEWORTHY Lymphatic integrity plays a critical role in small intestinal homeostasis. Acute intestinal insult in a mouse model of acute ileitis causes morphological and functional changes in mesenteric and intestinal lymphatic vessels. While some of the changes significantly regressed during inflammation resolution, others persisted, including lymphangiogenesis and altered dendritic cell function and movement, potentially increasing susceptibility to the recurrence of gastrointestinal inflammation.

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Quiescent, Slow-Cycling Stem Cell Populations in Cancer: A Review of the Evidence and Discussion of Significance

Journal of Oncology ◽

10.1155/2011/396076 ◽

2011 ◽

Vol 2011 ◽

pp. 1-11 ◽

Cited By ~ 159

Author(s):

Nathan Moore ◽

Stephen Lyle

Keyword(s):

Cell Cycle ◽

Stem Cells ◽

Stem Cell ◽

Cancer Stem Cells ◽

Adult Stem Cells ◽

Cell Populations ◽

Proliferative Potential ◽

Cell Cycle Regulators ◽

Slow Cycling ◽

Stem Cell Populations

Long-lived cancer stem cells (CSCs) with indefinite proliferative potential have been identified in multiple epithelial cancer types. These cells are likely derived from transformed adult stem cells and are thought to share many characteristics with their parental population, including a quiescent slow-cycling phenotype. Various label-retaining techniques have been used to identify normal slow cycling adult stem cell populations and offer a unique methodology to functionally identify and isolate cancer stem cells. The quiescent nature of CSCs represents an inherent mechanism that at least partially explains chemotherapy resistance and recurrence in posttherapy cancer patients. Isolating and understanding the cell cycle regulatory mechanisms of quiescent cancer cells will be a key component to creation of future therapies that better target CSCs and totally eradicate tumors. Here we review the evidence for quiescent CSC populations and explore potential cell cycle regulators that may serve as future targets for elimination of these cells.

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