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

2017 ◽  
Vol 31 (S1) ◽  
Author(s):  
Kunihiro Kishida ◽  
Sarah Pearce ◽  
Shiyan Yu ◽  
Nan Gao ◽  
Ronaldo Ferraris
Keyword(s):  
Stem Cells ◽  
Nutrient Sensing ◽  
Intestinal Stem Cells ◽  
Small Intestinal

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

2017 ◽  
Vol 312 (6) ◽  
pp. G592-G605 ◽  
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.

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

2014 ◽  
Vol 55 (2) ◽  
pp. 381-390 ◽  
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

ALX-0600, a glucagon-like peptide-2 analogue, protects small intestinal stem cells from radiation damage

2003 ◽  
Vol 124 (4) ◽  
pp. A609-A610 ◽  
Author(s):  
Christopher S. Potten ◽  
Sarah Williamsom ◽  
Demchyshyn Lidia L. ◽  
Catherine S. Booth
Keyword(s):  
Stem Cells ◽  
Radiation Damage ◽  
Intestinal Stem Cells ◽  
Glucagon Like Peptide ◽  
Small Intestinal

scholarly journals Delayed activation of the DNA replication licensing system in Lgr5(+) intestinal stem cells

2017 ◽  
Author(s):  
T.D. Carroll ◽  
I.P. Newton ◽  
Y. Chen ◽  
J.J. Blow ◽  
I. Näthke
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Dna Replication ◽  
Intestinal Epithelium ◽  
Intestinal Stem Cells ◽  
Temporal Window ◽  
Restriction Point ◽  
Interphase Cells ◽  
Small Intestinal ◽  
Functional Restriction

ABSTRACTDuring late mitosis and early G1, replication origins are licensed for replication by binding to double hexamers of MCM2-7. Here, we investigate how licensing and proliferative commitment are coupled in the small-intestinal epithelium. We developed a method for identifying cells in intact tissue containing DNA-bound MCM2-7. Interphase cells above the transit-amplifying compartment had no DNA-bound MCM2-7, but still expressed MCM2-7 protein, suggesting that licensing is inhibited immediately upon differentiation. Strikingly, we found most proliferative Lgr5(+) stem cells are in an unlicensed state. This suggests that the elongated cell-cycle of intestinal stem-cells is caused by an increased G1 length, characterised by dormant periods with unlicensed origins. Significantly, the unlicensed state is lost In Apc mutant epithelium, which lacks a functional restriction point, causing licensing immediately upon G1 entry. We propose that the unlicensed G1 of intestinal stem cells creates a temporal window when proliferative fate decisions can be made.

scholarly journals Teduglutide ([Gly2]GLP-2) protects small intestinal stem cells from radiation damage

2004 ◽  
Vol 37 (6) ◽  
pp. 385-400 ◽  
Author(s):  
C. Booth ◽  
D. Booth ◽  
S. Williamson ◽  
L. L. Demchyshyn ◽  
C. S. Potten
Keyword(s):  
Stem Cells ◽  
Radiation Damage ◽  
Intestinal Stem Cells ◽  
Small Intestinal

scholarly journals Update on small intestinal stem cells

2013 ◽  
Vol 19 (29) ◽  
pp. 4671 ◽  
Author(s):  
Valentina Tesori
Keyword(s):  
Stem Cells ◽  
Intestinal Stem Cells ◽  
Small Intestinal

Transplantation of small intestinal stem cells after genetic modification

1995 ◽  
Vol 108 (4) ◽  
pp. A1238
Author(s):  
HRH Patel ◽  
CH Brierley ◽  
B Burchell ◽  
J Nicholson ◽  
R Hay ◽  
...  
Keyword(s):  
Stem Cells ◽  
Genetic Modification ◽  
Intestinal Stem Cells ◽  
Small Intestinal
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