scholarly journals Influence of Growth Hormone and Glutamine on Intestinal Stem Cells: A Narrative Review

Nutrients ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1941 ◽  
Author(s):  
Yun Chen ◽  
Ya-Hui Tsai ◽  
Bor-Jiun Tseng ◽  
Sheng-Hong Tseng
Keyword(s):  
Stem Cells ◽  
Growth Hormone ◽  
Intestinal Mucosa ◽  
Synergistic Effects ◽  
Paneth Cells ◽  
Intestinal Stem Cells ◽  
Similar Degree ◽  
Gh Treatment ◽  
Mucosal Growth ◽  
Crypt Cells

Growth hormone (GH) and glutamine (Gln) stimulate the growth of the intestinal mucosa. GH activates the proliferation of intestinal stem cells (ISCs), enhances the formation of crypt organoids, increases ISC stemness markers in the intestinal organoids, and drives the differentiation of ISCs into Paneth cells and enterocytes. Gln enhances the proliferation of ISCs and increases crypt organoid formation; however, it mainly acts on the post-proliferation activity of ISCs to maintain the stability of crypt organoids and the intestinal mucosa, as well as to stimulate the differentiation of ISCs into goblet cells and possibly Paneth cells and enteroendocrine cells. Since GH and Gln have differential effects on ISCs. Their use in combination may have synergistic effects on ISCs. In this review, we summarize the evidence of the actions of GH and/or Gln on crypt cells and ISCs in the literature. Overall, most studies demonstrated that GH and Gln in combination exerted synergistic effects to activate the proliferation of crypt cells and ISCs and enhance crypt organoid formation and mucosal growth. This treatment influenced the proliferation of ISCs to a similar degree as GH treatment alone and the differentiation of ISCs to a similar degree as Gln treatment alone.

Distinct Effects of Growth Hormone and Glutamine on Activation of Intestinal Stem Cells

2017 ◽  
pp. 014860711770943 ◽  
Author(s):  
Yun Chen ◽  
Sheng-Hong Tseng ◽  
Chao-Ling Yao ◽  
Chuan Li ◽  
Ya-Hui Tsai
Keyword(s):  
Stem Cells ◽  
Growth Hormone ◽  
Intestinal Stem Cells

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 The cellular niche for intestinal stem cells: a team effort

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Guoli Zhu ◽  
Jiulong Hu ◽  
Rongwen Xi
Keyword(s):  
Stem Cells ◽  
Paneth Cells ◽  
Intestinal Stem Cells ◽  
Self Renewal ◽  
Epithelial Compartment ◽  
Definition Of ◽  
Cellular Components ◽  
Identification And Characterization ◽  
Mammalian Intestine

AbstractThe rapidly self-renewing epithelium in the mammalian intestine is maintained by multipotent intestinal stem cells (ISCs) located at the bottom of the intestinal crypt that are interspersed with Paneth cells in the small intestine and Paneth-like cells in the colon. The ISC compartment is also closely associated with a sub-epithelial compartment that contains multiple types of mesenchymal stromal cells. With the advances in single cell and gene editing technologies, rapid progress has been made for the identification and characterization of the cellular components of the niche microenvironment that is essential for self-renewal and differentiation of ISCs. It has become increasingly clear that a heterogeneous population of mesenchymal cells as well as the Paneth cells collectively provide multiple secreted niche signals to promote ISC self-renewal. Here we review and summarize recent advances in the regulation of ISCs with a main focus on the definition of niche cells that sustain ISCs.

scholarly journals MLL1 is required for maintenance of intestinal stem cells and the expression of the cell adhesion molecule JAML

2020 ◽  
Author(s):  
Neha Goveas ◽  
Claudia Waskow ◽  
Kathrin Arndt ◽  
Julian Heuberger ◽  
Qinyu Zhang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Adhesion Molecule ◽  
Adult Stem Cells ◽  
Paneth Cells ◽  
Intestinal Stem Cells ◽  
Epigenetic Mark ◽  
Hematopoietic Stem ◽  
Histone 3 ◽  
H3k4 Methyltransferases

AbstractEpigenetic control is crucial for lineage-specific gene expression that creates cellular identity during mammalian development and in adult organism. Histone 3 lysine 4 methylation (H3K4) is a universal epigenetic mark. Mixed lineage leukemia (MLL1) is the founding member of the mammalian family of H3K4 methyltransferases. It was originally discovered as the main gene mutated in early onset leukemias and then found to be required for hematopoietic stem cell development and maintenance. However, the roles of MLL1 in non-hematopoietic tissues remain largely unexplored. To bypass hematopoietic lethality, we used bone marrow transplantation and conditional mutagenesis to discover that the most overt phenotype in Mll1-mutant mice is intestinal failure. Loss of MLL1 is accompanied by a differentiation bias towards the secretory lineage with increased numbers of goblet cells. MLL1 is expressed in intestinal stem cells (ISCs) and transit amplifying (TA) cells but at reduced levels in Paneth cells and not in the villus. MLL1 is required for the maintenance of intestinal stem cells (ISCs) and proliferation in the crypt. Transcriptome analysis implicate MLL1-dependent expression in ISCs of several transcription factors including Pitx2, Gata4, Foxa1 and Onecut2, and also a cell adhesion molecule, Jaml. Reactive transcriptome changes in Paneth cells and organoids imply that JAML plays a key role in the crypt stem cell niche. All known postnatal functions of MLL1 relate to stem cell maintenance and lineage decisions thereby highlighting the suggestion that MLL1 is a master stem cell regulator.Author SummaryThe ability of adult stem cells to produce functional progenies through differentiation is critical to maintain function and integrity of organs. A fundamental challenge is to identify factors that control the transition from self-renewal to the differentiated state. Epigenetic factors amongst others can fullfill such a role. Methylation of histone 3 on lysine 4 (H3K4) is a posttranslational epigenetic modification that is associated with actively transcribed genes. In mammals, this epigenetic mark is catalyzed by one of six H3K4 methyltransferases, including the founding member of the family, MLL1. MLL1 is important for the precise functioning of the hematopoietic stem cell compartment. This raises the possibility of similar functions in other adult stem cell compartments. Due to its intense self-renewal kinetics and its simple repetitive architecture, the intestinal epithelium serves as a prime model for studying adult stem cells. We demonstrate that MLL1 controls intestinal stem cell proliferation and differentiation. Additionally, transcriptome analysis suggests a pertubation in the close interaction between intestinal stem cells and neighbouring Paneth cells through loss of junction adhesion molecule like (JAML). Our work sheds new light on the function of MLL1 for the control of intestinal stem cell identity.

scholarly journals MLL1 is required for maintenance of intestinal stem cells

PLoS Genetics ◽  
2021 ◽  
Vol 17 (12) ◽  
pp. e1009250
Author(s):  
Neha Goveas ◽  
Claudia Waskow ◽  
Kathrin Arndt ◽  
Julian Heuberger ◽  
Qinyu Zhang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Stem Cell ◽  
Stress Responses ◽  
Expression Patterns ◽  
Paneth Cells ◽  
Intestinal Stem Cells ◽  
Causative Mutation ◽  
Hematopoietic Stem ◽  
Conditional Mutagenesis

Epigenetic mechanisms are gatekeepers for the gene expression patterns that establish and maintain cellular identity in mammalian development, stem cells and adult homeostasis. Amongst many epigenetic marks, methylation of histone 3 lysine 4 (H3K4) is one of the most widely conserved and occupies a central position in gene expression. Mixed lineage leukemia 1 (MLL1/KMT2A) is the founding mammalian H3K4 methyltransferase. It was discovered as the causative mutation in early onset leukemia and subsequently found to be required for the establishment of definitive hematopoiesis and the maintenance of adult hematopoietic stem cells. Despite wide expression, the roles of MLL1 in non-hematopoietic tissues remain largely unexplored. To bypass hematopoietic lethality, we used bone marrow transplantation and conditional mutagenesis to discover that the most overt phenotype in adult Mll1-mutant mice is intestinal failure. MLL1 is expressed in intestinal stem cells (ISCs) and transit amplifying (TA) cells but not in the villus. Loss of MLL1 is accompanied by loss of ISCs and a differentiation bias towards the secretory lineage with increased numbers and enlargement of goblet cells. Expression profiling of sorted ISCs revealed that MLL1 is required to promote expression of several definitive intestinal transcription factors including Pitx1, Pitx2, Foxa1, Gata4, Zfp503 and Onecut2, as well as the H3K27me3 binder, Bahcc1. These results were recapitulated using conditional mutagenesis in intestinal organoids. The stem cell niche in the crypt includes ISCs in close association with Paneth cells. Loss of MLL1 from ISCs promoted transcriptional changes in Paneth cells involving metabolic and stress responses. Here we add ISCs to the MLL1 repertoire and observe that all known functions of MLL1 relate to the properties of somatic stem cells, thereby highlighting the suggestion that MLL1 is a master somatic stem cell regulator.

Redundant Sources of Wnt Regulate Intestinal Stem Cells and Promote Formation of Paneth Cells

2012 ◽  
Vol 143 (6) ◽  
pp. 1518-1529.e7 ◽  
Author(s):  
Henner F. Farin ◽  
Johan H. Van Es ◽  
Hans Clevers
Keyword(s):  
Stem Cells ◽  
Paneth Cells ◽  
Intestinal Stem Cells
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