Cellular kinetics of gastrointestinal mucosa, with special reference to gut endocrine cells.

Inokuchi, Hideto; Fujimoto, Sotaro; Kawai, Keiichi

doi:10.1679/aohc.46.137

Cited by 37 publications

(29 citation statements)

References 60 publications

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“…Nonlinear regression analysis yielded a value of 2.4 days (95% confidence interval 0.2-1.0 week) for the half-life of duodenal crypt cells. This value is in very good agreement with the known cell kinetics in the rat intestine (Herbst and Koldovsky 1972;Inokuchi et al 1983;Holt et al 1983), showing that BrdU 'heredity transmission' by cell divisions does not interfere with the applicability of our method. It has been estimated that 5-6 cell divisions are required before the threshold of detectability is reached when using flow cytometric analysis of BrdU in single cell preparations (Bonhoeffer et al 2000).…”

Section: Resultssupporting

confidence: 87%

Histological assessment of cellular half-life in tissues in vivo

Erben

Odörfer

Siebenhütter

et al. 2008

Histochem Cell Biol

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The assessment of cellular half-life is of fundamental importance for cell biology and biomedicine. Here, we show that cellular half-life in tissues can be histologically measured under steady state conditions in vivo by analyzing the loss of 5-bromo-2'-deoxyuridine (BrdU)-labeled cells over time after withdrawal of long-term BrdU labeling. To achieve efficient continuous cell labeling, we implanted BrdU-containing subcutaneous slow-release pellets into 12-month-old male Fischer 344 rats, delivering BrdU at a dose of 75 mg/kg per day over 1 (n=20) or 3 weeks (n=20). Four to five rats each were killed directly after the labeling or 1, 3, and 7 weeks post-labeling. Cellular half-life after withdrawal of BrdU was analyzed by nonlinear regression analysis of the labeling index, using a model of one-phase exponential decay. We initially validated our technique in the duodenum, where we determined a half-life of 2.4 days for crypt cells. Next, we applied this method to other tissues, and found a half-life of 2.2 weeks for cardiac endothelial cells, and of 5-6 days for pancreatic duct cells. In conclusion, we believe that this novel approach is an important step forward in the histological assessment of cellular half-life.

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Section: Resultssupporting

confidence: 87%

Histological assessment of cellular half-life in tissues in vivo

Erben

Odörfer

Siebenhütter

et al. 2008

Histochem Cell Biol

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“…This is earlier than GLP-1 or secretin expressing cells, which did not become BrdU-labeled until 12-24 hr after injection (Fig. 3, right panel; Aiken and Roth, 1993;Inokuchi et al, 1983). Although BrdU labeling of secretin and GLP-1 occurs at about the same time after BrdU injection, the majority of GLP-1 expressing cells are located in the crypts and lower villi, whereas the majority of secretin expressing cells are located in the upper villi.…”

Section: Discussionmentioning

confidence: 86%

Immunohistochemical studies indicate multiple enteroendocrine cell differentiation pathways in the mouse proximal small intestine

Aiken

Kisslinger

Roth

1994

Developmental Dynamics

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The enteroendocrine cell system of the mammalian gastrointestinal tract is comprised of at least 16 different subpopulations. Each subpopulation shows a characteristic distribution along both the crypt-villus and cephalocaudal axes. In both the small intestine and colon of adult mice, multilabel immunohistochemistry has demonstrated that two or more neuroendocrine products can be coexpressed in various combinations in single cells along the crypt-villus axis, suggesting that enteroendocrine phenotypes may be actively regulated. Using bromodeoxyuridine (BrdU) incorporation and multilabel immunohistochcmistry, we have previously demonstrated an enteroendocrine cell differentiation pathway consisting of two subpopulations of cells in the mouse proximal small intestinmne involving the sequential expression of substance P, serotonin, and secretin in cells migrating out of the crypts into the villi, and a second involving the expression of substance P and serotonin in cells which remain in the crypts. In this report, we use double label immunohistochemistry and BrdU incorporation to define the temporal and spatial interrelationships between gastrin, cholecystokinin (CCK), glucagon-like peptide-1 (GLP-I), and gastric inhibitory peptide (GIP) immunoreactive cells in the mouse proximal small intestine. The expression of these products was compared with that of substance P, serotonin, and secretin. Minimal overlap of expression was found in cells immunoreactive for substance P or serotonin with gastrin, CCK, GLP-1, or GIP; however, secretin was found colocalized in villus-associated gastrin, CCK, and GLP-1 containing cells. We demonstrate that, similar to the bidirectionally migrating substance P and serotonin expressing cells, gastrin, CCK, GLP-1, and secretin are expressed in upwardly migrating cells, and gastrin, CCK, and GLP-1 are expressed in downwardly migrating cells that fail to express secretin. GIP containing cells only rarely coexpressed any of the products examined, but were found both in the villi and the crypts, suggesting both upwardly and downwardly migrating populations. These findings demonstrate several novel enteroendocrine cell differentiation pathways. In addition, the expression of secretin 0 1994 WILEY-LISS, INC.in the villi, but not in the crypts, by two otherwise distinct differentiation pathways, and the lack of secretin expression by villus-associated GIP expressing cells, suggests that local factors present in the crypts and/or on the villi are necessary, but not sufficient, for secretin expression.

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“…Although individual cells could not be followed across time to show directly this proposed phenotypic switching, the bulk of evidence suggests that a portion of the substance P, serotonin, and secretin immunoreactive cell populations traverse this pathway. This hypothesis is supported by the relative lack of substance P immunoreactive cells in the upper villus, the failure t o find crypt-associated secretin cells, and the long lag period (24-48 hr) between BrdU or 3H-thymidine injection and the identification of secretin labeled cells on the villus (Inokuchi et al, 1983). Clearly, since the number of substance P, serotonin, and secretin expressing cells and their relative coexpression patterns vary markedly from region to region within the gut, additional differentiation pathways for these cell populations must exist.…”

Section: Discussionmentioning

confidence: 96%

Temporal differentiation and migration of substance P, serotonin, and secretin immunoreactive enteroendocrine cells in the mouse proximal small intestine

Aiken

Roth

1992

Developmental Dynamics

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Precise spatial interrelationships exist between substance P, serotonin, and secretin containing enteroendocrine cells in the gastrointestinal tract of mice. In the proximal small intestine these products are coexpressed in various combinations in single enteroendocrine cells along the crypt to villus axis in a pattern that suggests the sequential expression of substance P, serotonin, and secretin. In this report we use bromodeoxyuridine (BrdU) and multilabeling immunohistochemistry to define the temporal and spatial interrelationships between substance P, serotonin, and secretin immunoreactive cells in the mouse proximal small intestine. Our findings demonstrate the sequential expression of substance P, serotonin, and secretin in a population of upwardly migrating enteroendocrine cells and, furthermore, identify a population of crypt associated cells coexpressing substance P and serotonin that fails to traverse this pathway. The lack of secretin immunoreactive cells in the crypts suggests that local factors present in the crypts and/or on villi regulate secretin expression. The combined use of BrdU and multilabeling immunohistochemistry provides a method for defining enteroendocrine cell differentiation pathways throughout the gastrointestinal tract. 0 1992 Wiley-Liss, Inc.

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Cellular kinetics of gastrointestinal mucosa, with special reference to gut endocrine cells.

Cited by 37 publications

References 60 publications

Histological assessment of cellular half-life in tissues in vivo

Histological assessment of cellular half-life in tissues in vivo

Immunohistochemical studies indicate multiple enteroendocrine cell differentiation pathways in the mouse proximal small intestine

Temporal differentiation and migration of substance P, serotonin, and secretin immunoreactive enteroendocrine cells in the mouse proximal small intestine

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