Interplay between metabolic identities in the intestinal crypt supports stem cell function
The glycolytic activity of Paneth cells provides lactate, which is required by self-renewing intestinal stem cells for oxidative metabolism to activate p38 MAP kinase, ensuring regeneration of a mature crypt. Metabolism and gut regeneration Small intestine crypts are regenerated throughout life than...
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| Vydáno v: | Nature (London) Ročník 543; číslo 7645; s. 424 - 427 |
|---|---|
| Hlavní autoři: | , , , , , , , , , , , , |
| Médium: | Journal Article |
| Jazyk: | angličtina |
| Vydáno: |
London
Nature Publishing Group UK
16.03.2017
Nature Publishing Group |
| Témata: | |
| ISSN: | 0028-0836, 1476-4687, 1476-4687 |
| On-line přístup: | Získat plný text |
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| Abstract | The glycolytic activity of Paneth cells provides lactate, which is required by self-renewing intestinal stem cells for oxidative metabolism to activate p38 MAP kinase, ensuring regeneration of a mature crypt.
Metabolism and gut regeneration
Small intestine crypts are regenerated throughout life thanks to self-renewing stem cells located at the bottom of crypts. Differentiated Paneth cells provide the signalling molecules that modulate the regenerative properties of these stem cells. The influence of metabolism on the self-renewal of the crypt has not been studied in great detail. Burgering and colleagues now show that, whereas intestinal stem cells rely on mitochondrial activity for their metabolic needs, Paneth cells use glycolysis, a process that provides the lactate that is required by the stem cells for their oxidative metabolism. This activates the p38 MAP kinase to ensure regeneration of a mature crypt. The findings suggest that the metabolism of certain intestinal cells has an important role in supporting stem cell function.
The small intestinal epithelium self-renews every four or five days. Intestinal stem cells (Lgr5
+
crypt base columnar cells (CBCs)) sustain this renewal and reside between terminally differentiated Paneth cells at the bottom of the intestinal crypt
1
. Whereas the signalling requirements for maintaining stem cell function and crypt homeostasis have been well studied, little is known about how metabolism contributes to epithelial homeostasis. Here we show that freshly isolated Lgr5
+
CBCs and Paneth cells from the mouse small intestine display different metabolic programs. Compared to Paneth cells, Lgr5
+
CBCs display high mitochondrial activity. Inhibition of mitochondrial activity in Lgr5
+
CBCs or inhibition of glycolysis in Paneth cells strongly affects stem cell function, as indicated by impaired organoid formation. In addition, Paneth cells support stem cell function by providing lactate to sustain the enhanced mitochondrial oxidative phosphorylation in the Lgr5
+
CBCs. Mechanistically, we show that oxidative phosphorylation stimulates p38 MAPK activation by mitochondrial reactive oxygen species signalling, thereby establishing the mature crypt phenotype. Together, our results reveal a critical role for the metabolic identity of Lgr5
+
CBCs and Paneth cells in supporting optimal stem cell function, and we identify mitochondria and reactive oxygen species signalling as a driving force of cellular differentiation. |
|---|---|
| AbstractList | The small intestinal epithelium self-renews every four or five days. Intestinal stem cells (Lgr5
crypt base columnar cells (CBCs)) sustain this renewal and reside between terminally differentiated Paneth cells at the bottom of the intestinal crypt. Whereas the signalling requirements for maintaining stem cell function and crypt homeostasis have been well studied, little is known about how metabolism contributes to epithelial homeostasis. Here we show that freshly isolated Lgr5
CBCs and Paneth cells from the mouse small intestine display different metabolic programs. Compared to Paneth cells, Lgr5
CBCs display high mitochondrial activity. Inhibition of mitochondrial activity in Lgr5
CBCs or inhibition of glycolysis in Paneth cells strongly affects stem cell function, as indicated by impaired organoid formation. In addition, Paneth cells support stem cell function by providing lactate to sustain the enhanced mitochondrial oxidative phosphorylation in the Lgr5
CBCs. Mechanistically, we show that oxidative phosphorylation stimulates p38 MAPK activation by mitochondrial reactive oxygen species signalling, thereby establishing the mature crypt phenotype. Together, our results reveal a critical role for the metabolic identity of Lgr5
CBCs and Paneth cells in supporting optimal stem cell function, and we identify mitochondria and reactive oxygen species signalling as a driving force of cellular differentiation. The glycolytic activity of Paneth cells provides lactate, which is required by self-renewing intestinal stem cells for oxidative metabolism to activate p38 MAP kinase, ensuring regeneration of a mature crypt. Metabolism and gut regeneration Small intestine crypts are regenerated throughout life thanks to self-renewing stem cells located at the bottom of crypts. Differentiated Paneth cells provide the signalling molecules that modulate the regenerative properties of these stem cells. The influence of metabolism on the self-renewal of the crypt has not been studied in great detail. Burgering and colleagues now show that, whereas intestinal stem cells rely on mitochondrial activity for their metabolic needs, Paneth cells use glycolysis, a process that provides the lactate that is required by the stem cells for their oxidative metabolism. This activates the p38 MAP kinase to ensure regeneration of a mature crypt. The findings suggest that the metabolism of certain intestinal cells has an important role in supporting stem cell function. The small intestinal epithelium self-renews every four or five days. Intestinal stem cells (Lgr5 + crypt base columnar cells (CBCs)) sustain this renewal and reside between terminally differentiated Paneth cells at the bottom of the intestinal crypt 1 . Whereas the signalling requirements for maintaining stem cell function and crypt homeostasis have been well studied, little is known about how metabolism contributes to epithelial homeostasis. Here we show that freshly isolated Lgr5 + CBCs and Paneth cells from the mouse small intestine display different metabolic programs. Compared to Paneth cells, Lgr5 + CBCs display high mitochondrial activity. Inhibition of mitochondrial activity in Lgr5 + CBCs or inhibition of glycolysis in Paneth cells strongly affects stem cell function, as indicated by impaired organoid formation. In addition, Paneth cells support stem cell function by providing lactate to sustain the enhanced mitochondrial oxidative phosphorylation in the Lgr5 + CBCs. Mechanistically, we show that oxidative phosphorylation stimulates p38 MAPK activation by mitochondrial reactive oxygen species signalling, thereby establishing the mature crypt phenotype. Together, our results reveal a critical role for the metabolic identity of Lgr5 + CBCs and Paneth cells in supporting optimal stem cell function, and we identify mitochondria and reactive oxygen species signalling as a driving force of cellular differentiation. The small intestinal epithelium self-renews every four or five days. Intestinal stem cells (Lgr5^sup +^ crypt base columnar cells (CBCs)) sustain this renewal and reside between terminally differentiated Paneth cells at the bottom of the intestinal crypt1. Whereas the signalling requirements for maintaining stem cell function and crypt homeostasis have been well studied, little is known about how metabolism contributes to epithelial homeostasis. Here we show that freshly isolated Lgr5^sup +^ CBCs and Paneth cells from the mouse small intestine display different metabolic programs. Compared to Paneth cells, Lgr5^sup +^ CBCs display high mitochondrial activity. Inhibition of mitochondrial activity in Lgr5^sup +^ CBCs or inhibition of glycolysis in Paneth cells strongly affects stem cell function, as indicated by impaired organoid formation. In addition, Paneth cells support stem cell function by providing lactate to sustain the enhanced mitochondrial oxidative phosphorylation in the Lgr5^sup +^ CBCs. Mechanistically, we show that oxidative phosphorylation stimulates p38 MAPK activation by mitochondrial reactive oxygen species signalling, thereby establishing the mature crypt phenotype. Together, our results reveal a critical role for the metabolic identity of Lgr5^sup +^ CBCs and Paneth cells in supporting optimal stem cell function, and we identify mitochondria and reactive oxygen species signalling as a driving force of cellular differentiation. The small intestinal epithelium self-renews every four or five days. Intestinal stem cells (Lgr5+ crypt base columnar cells (CBCs)) sustain this renewal and reside between terminally differentiated Paneth cells at the bottom of the intestinal crypt. Whereas the signalling requirements for maintaining stem cell function and crypt homeostasis have been well studied, little is known about how metabolism contributes to epithelial homeostasis. Here we show that freshly isolated Lgr5+ CBCs and Paneth cells from the mouse small intestine display different metabolic programs. Compared to Paneth cells, Lgr5+ CBCs display high mitochondrial activity. Inhibition of mitochondrial activity in Lgr5+ CBCs or inhibition of glycolysis in Paneth cells strongly affects stem cell function, as indicated by impaired organoid formation. In addition, Paneth cells support stem cell function by providing lactate to sustain the enhanced mitochondrial oxidative phosphorylation in the Lgr5+ CBCs. Mechanistically, we show that oxidative phosphorylation stimulates p38 MAPK activation by mitochondrial reactive oxygen species signalling, thereby establishing the mature crypt phenotype. Together, our results reveal a critical role for the metabolic identity of Lgr5+ CBCs and Paneth cells in supporting optimal stem cell function, and we identify mitochondria and reactive oxygen species signalling as a driving force of cellular differentiation.The small intestinal epithelium self-renews every four or five days. Intestinal stem cells (Lgr5+ crypt base columnar cells (CBCs)) sustain this renewal and reside between terminally differentiated Paneth cells at the bottom of the intestinal crypt. Whereas the signalling requirements for maintaining stem cell function and crypt homeostasis have been well studied, little is known about how metabolism contributes to epithelial homeostasis. Here we show that freshly isolated Lgr5+ CBCs and Paneth cells from the mouse small intestine display different metabolic programs. Compared to Paneth cells, Lgr5+ CBCs display high mitochondrial activity. Inhibition of mitochondrial activity in Lgr5+ CBCs or inhibition of glycolysis in Paneth cells strongly affects stem cell function, as indicated by impaired organoid formation. In addition, Paneth cells support stem cell function by providing lactate to sustain the enhanced mitochondrial oxidative phosphorylation in the Lgr5+ CBCs. Mechanistically, we show that oxidative phosphorylation stimulates p38 MAPK activation by mitochondrial reactive oxygen species signalling, thereby establishing the mature crypt phenotype. Together, our results reveal a critical role for the metabolic identity of Lgr5+ CBCs and Paneth cells in supporting optimal stem cell function, and we identify mitochondria and reactive oxygen species signalling as a driving force of cellular differentiation. |
| Audience | Academic |
| Author | Fodde, Riccardo Oost, Koen C. Sacchetti, Andrea Rodríguez-Colman, Maria J. Hornsveld, Marten Verhoeven-Duif, Nanda Meerlo, Maaike Gerrits, Johan Burgering, Boudewijn M. T. Stigter, Edwin Pras-Raves, Mia Schewe, Matthias Snippert, Hugo J. |
| Author_xml | – sequence: 1 givenname: Maria J. surname: Rodríguez-Colman fullname: Rodríguez-Colman, Maria J. organization: Molecular Cancer Research, Center Molecular Medicine, University Medical Center Utrecht – sequence: 2 givenname: Matthias surname: Schewe fullname: Schewe, Matthias organization: Department of Pathology, Erasmus MC Cancer Institute, Erasmus University Medical Center – sequence: 3 givenname: Maaike surname: Meerlo fullname: Meerlo, Maaike organization: Molecular Cancer Research, Center Molecular Medicine, University Medical Center Utrecht – sequence: 4 givenname: Edwin surname: Stigter fullname: Stigter, Edwin organization: Molecular Cancer Research, Center Molecular Medicine, University Medical Center Utrecht – sequence: 5 givenname: Johan surname: Gerrits fullname: Gerrits, Johan organization: Department of Genetics and Center for Molecular Medicine – sequence: 6 givenname: Mia surname: Pras-Raves fullname: Pras-Raves, Mia organization: Department of Genetics and Center for Molecular Medicine – sequence: 7 givenname: Andrea surname: Sacchetti fullname: Sacchetti, Andrea organization: Department of Pathology, Erasmus MC Cancer Institute, Erasmus University Medical Center – sequence: 8 givenname: Marten surname: Hornsveld fullname: Hornsveld, Marten organization: Molecular Cancer Research, Center Molecular Medicine, University Medical Center Utrecht – sequence: 9 givenname: Koen C. surname: Oost fullname: Oost, Koen C. organization: Molecular Cancer Research, Center Molecular Medicine, University Medical Center Utrecht – sequence: 10 givenname: Hugo J. surname: Snippert fullname: Snippert, Hugo J. organization: Molecular Cancer Research, Center Molecular Medicine, University Medical Center Utrecht – sequence: 11 givenname: Nanda surname: Verhoeven-Duif fullname: Verhoeven-Duif, Nanda organization: Department of Genetics and Center for Molecular Medicine – sequence: 12 givenname: Riccardo surname: Fodde fullname: Fodde, Riccardo organization: Department of Pathology, Erasmus MC Cancer Institute, Erasmus University Medical Center – sequence: 13 givenname: Boudewijn M. T. surname: Burgering fullname: Burgering, Boudewijn M. T. email: b.m.t.burgering@umcutrecht.nl organization: Molecular Cancer Research, Center Molecular Medicine, University Medical Center Utrecht |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/28273069$$D View this record in MEDLINE/PubMed |
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| Cites_doi | 10.1038/nature08313 10.1016/j.cell.2014.04.039 10.1053/j.gastro.2011.07.050 10.1053/j.gastro.2010.01.005 10.1016/j.freeradbiomed.2003.12.019 10.1038/nmeth.1212 10.3109/10715762.2013.821200 10.1038/nature07935 10.1038/nature09637 10.1038/nrc2694 10.1038/nmeth.2737 10.1038/sj.bjc.6604554 10.1371/journal.pone.0028536 10.1093/nar/gkv380 10.1016/j.cmet.2011.08.007 10.1016/j.celrep.2013.09.005 10.1016/j.bbabio.2013.07.008 10.1073/pnas.1414135111 10.1016/j.stem.2011.02.020 10.1016/j.stem.2016.05.023 10.1021/ac051437y 10.1089/ars.2013.5300 10.1038/nature06196 10.1038/nature11163 10.1126/science.1234852 10.1053/j.gastro.2015.06.007 10.1371/journal.pone.0050679 10.1038/nrm3721 10.1016/j.freeradbiomed.2011.08.035 10.1038/emboj.2011.401 10.1126/scisignal.2003638 10.1016/j.stem.2015.12.005 10.1016/j.stem.2013.09.015 10.3791/52531 10.1016/S0022-3565(24)37225-8 |
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| References_xml | – volume: 461 start-page: 537 year: 2009 end-page: 541 ident: CR3 article-title: Reactive oxygen species prime haematopoietic progenitors for differentiation publication-title: Nature doi: 10.1038/nature08313 – volume: 157 start-page: 1724 year: 2014 end-page: 1734 ident: CR22 article-title: High-sensitivity measurements of multiple kinase activities in live single cells publication-title: Cell doi: 10.1016/j.cell.2014.04.039 – volume: 141 start-page: 1762 year: 2011 end-page: 1772 ident: CR14 article-title: Long-term expansion of epithelial organoids from human colon, adenoma, adenocarcinoma, and Barrett’s epithelium publication-title: Gastroenterology doi: 10.1053/j.gastro.2011.07.050 – volume: 138 start-page: 1255 year: 2010 end-page: 1265 ident: CR26 article-title: Distinct effects of p38α deletion in myeloid lineage and gut epithelia in mouse models of inflammatory bowel disease publication-title: Gastroenterology doi: 10.1053/j.gastro.2010.01.005 – volume: 36 start-page: 765 year: 2004 end-page: 773 ident: CR28 article-title: Reactive oxygen species derived from the mitochondrial respiratory chain are not responsible for the basal levels of oxidative base modifications observed in nuclear DNA of Mammalian cells publication-title: Free Radic. Biol. Med. doi: 10.1016/j.freeradbiomed.2003.12.019 – volume: 5 start-page: 553 year: 2008 end-page: 559 ident: CR19 article-title: Real-time imaging of the intracellular glutathione redox potential publication-title: Nat. Methods doi: 10.1038/nmeth.1212 – volume: 47 start-page: 905 year: 2013 end-page: 916 ident: CR20 article-title: p38 MAPK: a dual role in hepatocyte proliferation through reactive oxygen species publication-title: Free Radic. Res. doi: 10.3109/10715762.2013.821200 – volume: 459 start-page: 262 year: 2009 end-page: 265 ident: CR23 article-title: Single Lgr5 stem cells build crypt-villus structures without a mesenchymal niche publication-title: Nature doi: 10.1038/nature07935 – volume: 469 start-page: 415 year: 2011 end-page: 418 ident: CR10 article-title: Paneth cells constitute the niche for Lgr5 stem cells in intestinal crypts publication-title: Nature doi: 10.1038/nature09637 – volume: 9 start-page: 537 year: 2009 end-page: 549 ident: CR21 article-title: Signal integration by JNK and p38 MAPK pathways in cancer development publication-title: Nat. Rev. Cancer doi: 10.1038/nrc2694 – volume: 11 start-page: 106 year: 2014 end-page: 112 ident: CR9 article-title: Niche-independent high-purity cultures of Lgr5 intestinal stem cells and their progeny publication-title: Nat. Methods doi: 10.1038/nmeth.2737 – volume: 99 start-page: 989 year: 2008 end-page: 994 ident: CR16 article-title: Dichloroacetate (DCA) as a potential metabolic-targeting therapy for cancer publication-title: Br. J. Cancer doi: 10.1038/sj.bjc.6604554 – volume: 6 start-page: e28536 year: 2011 ident: CR18 article-title: Galactose enhances oxidative metabolism and reveals mitochondrial dysfunction in human primary muscle cells publication-title: PLoS One doi: 10.1371/journal.pone.0028536 – volume: 43 start-page: W251 year: 2015 end-page: W257 ident: CR36 article-title: MetaboAnalyst 3.0—making metabolomics more meaningful publication-title: Nucleic Acids Res. doi: 10.1093/nar/gkv380 – volume: 1846 start-page: 617 year: 2014 end-page: 629 ident: CR15 article-title: Dichloroacetate and cancer: new home for an orphan drug? publication-title: Biochim. Biophys. Acta – volume: 14 start-page: 537 year: 2011 end-page: 544 ident: CR4 article-title: Mitochondrial complex III ROS regulate adipocyte differentiation publication-title: Cell Metab. doi: 10.1016/j.cmet.2011.08.007 – volume: 5 start-page: 421 year: 2013 end-page: 432 ident: CR11 article-title: Identification of Lgr5-independent spheroid-generating progenitors of the mouse fetal intestinal epithelium publication-title: Cell Reports doi: 10.1016/j.celrep.2013.09.005 – volume: 1837 start-page: 51 year: 2014 end-page: 62 ident: CR17 article-title: Availability of the key metabolic substrates dictates the respiratory response of cancer cells to the mitochondrial uncoupling publication-title: Biochim. Biophys. Acta doi: 10.1016/j.bbabio.2013.07.008 – volume: 111 start-page: 13487 year: 2014 end-page: 13492 ident: CR29 article-title: Mitochondrial reactive oxygen species are scavenged by Cockayne syndrome B protein in human fibroblasts without nuclear DNA damage publication-title: Proc. Natl Acad. Sci. USA doi: 10.1073/pnas.1414135111 – volume: 8 start-page: 511 year: 2011 end-page: 524 ident: CR25 article-title: The intestinal stem cell signature identifies colorectal cancer stem cells and predicts disease relapse publication-title: Cell Stem Cell doi: 10.1016/j.stem.2011.02.020 – volume: 19 start-page: 38 year: 2016 end-page: 51 ident: CR24 article-title: Secreted phospholipases A2 are intestinal stem cell niche factors with distinct roles in homeostasis, inflammation, and cancer publication-title: Cell Stem Cell doi: 10.1016/j.stem.2016.05.023 – volume: 78 start-page: 779 year: 2006 end-page: 787 ident: CR35 article-title: XCMS: processing mass spectrometry data for metabolite profiling using nonlinear peak alignment, matching, and identification publication-title: Anal. Chem. doi: 10.1021/ac051437y – volume: 20 start-page: 1902 year: 2014 end-page: 1916 ident: CR27 article-title: Stem cells, redox signaling, and stem cell aging publication-title: Antioxid. Redox Signal. doi: 10.1089/ars.2013.5300 – volume: 449 start-page: 1003 year: 2007 end-page: 1007 ident: CR1 article-title: Identification of stem cells in small intestine and colon by marker gene publication-title: Nature doi: 10.1038/nature06196 – volume: 486 start-page: 490 year: 2012 end-page: 495 ident: CR6 article-title: mTORC1 in the Paneth cell niche couples intestinal stem-cell function to calorie intake publication-title: Nature doi: 10.1038/nature11163 – volume: 340 start-page: 1190 year: 2013 end-page: 1194 ident: CR13 article-title: Growing self-organizing mini-guts from a single intestinal stem cell: mechanism and applications publication-title: Science doi: 10.1126/science.1234852 – ident: CR31 – volume: 284 start-page: 215 year: 1998 end-page: 221 ident: CR32 article-title: Synthetic combined superoxide dismutase/catalase mimetics are protective as a delayed treatment in a rat stroke model: a key role for reactive oxygen species in ischemic brain injury publication-title: J. Pharmacol. Exp. Ther. – volume: 149 start-page: 1006 year: 2015 end-page: 1016 ident: CR30 article-title: FOXM1-induced PRX3 regulates stemness and survival of colon cancer cells via maintenance of mitochondrial function publication-title: Gastroenterology doi: 10.1053/j.gastro.2015.06.007 – volume: 7 start-page: e50679 year: 2012 ident: CR34 article-title: infection causes metabolic shifts in publication-title: PLoS One doi: 10.1371/journal.pone.0050679 – volume: 15 start-page: 19 year: 2014 end-page: 33 ident: CR8 article-title: Adult intestinal stem cells: critical drivers of epithelial homeostasis and regeneration publication-title: Nat. Rev. Mol. Cell Biol. doi: 10.1038/nrm3721 – volume: 51 start-page: 1943 year: 2011 end-page: 1951 ident: CR33 article-title: Measuring and H O with roGFP2-based redox probes publication-title: Free Radic. Biol. Med. doi: 10.1016/j.freeradbiomed.2011.08.035 – volume: 30 start-page: 4860 year: 2011 end-page: 4873 ident: CR2 article-title: UCP2 regulates energy metabolism and differentiation potential of human pluripotent stem cells publication-title: EMBO J. doi: 10.1038/emboj.2011.401 – volume: 6 start-page: ra8 year: 2013 ident: CR5 article-title: Mitochondrial reactive oxygen species promote epidermal differentiation and hair follicle development publication-title: Sci. Signal. doi: 10.1126/scisignal.2003638 – volume: 18 start-page: 25 year: 2016 end-page: 38 ident: CR7 article-title: Engineering stem cell organoids publication-title: Cell Stem Cell doi: 10.1016/j.stem.2015.12.005 – volume: 13 start-page: 734 year: 2013 end-page: 744 ident: CR12 article-title: Transplantation of expanded fetal intestinal progenitors contributes to colon regeneration after injury publication-title: Cell Stem Cell doi: 10.1016/j.stem.2013.09.015 – volume: 459 start-page: 262 year: 2009 ident: BFnature21673_CR23 publication-title: Nature doi: 10.1038/nature07935 – volume: 7 start-page: e50679 year: 2012 ident: BFnature21673_CR34 publication-title: PLoS One doi: 10.1371/journal.pone.0050679 – volume: 30 start-page: 4860 year: 2011 ident: BFnature21673_CR2 publication-title: EMBO J. doi: 10.1038/emboj.2011.401 – volume: 15 start-page: 19 year: 2014 ident: BFnature21673_CR8 publication-title: Nat. Rev. Mol. Cell Biol. doi: 10.1038/nrm3721 – volume: 11 start-page: 106 year: 2014 ident: BFnature21673_CR9 publication-title: Nat. Methods doi: 10.1038/nmeth.2737 – volume: 20 start-page: 1902 year: 2014 ident: BFnature21673_CR27 publication-title: Antioxid. Redox Signal. doi: 10.1089/ars.2013.5300 – ident: BFnature21673_CR31 doi: 10.3791/52531 – volume: 78 start-page: 779 year: 2006 ident: BFnature21673_CR35 publication-title: Anal. Chem. doi: 10.1021/ac051437y – volume: 157 start-page: 1724 year: 2014 ident: BFnature21673_CR22 publication-title: Cell doi: 10.1016/j.cell.2014.04.039 – volume: 19 start-page: 38 year: 2016 ident: BFnature21673_CR24 publication-title: Cell Stem Cell doi: 10.1016/j.stem.2016.05.023 – volume: 5 start-page: 421 year: 2013 ident: BFnature21673_CR11 publication-title: Cell Reports doi: 10.1016/j.celrep.2013.09.005 – volume: 6 start-page: e28536 year: 2011 ident: BFnature21673_CR18 publication-title: PLoS One doi: 10.1371/journal.pone.0028536 – volume: 111 start-page: 13487 year: 2014 ident: BFnature21673_CR29 publication-title: Proc. Natl Acad. Sci. USA doi: 10.1073/pnas.1414135111 – volume: 340 start-page: 1190 year: 2013 ident: BFnature21673_CR13 publication-title: Science doi: 10.1126/science.1234852 – volume: 51 start-page: 1943 year: 2011 ident: BFnature21673_CR33 publication-title: Free Radic. Biol. Med. doi: 10.1016/j.freeradbiomed.2011.08.035 – volume: 13 start-page: 734 year: 2013 ident: BFnature21673_CR12 publication-title: Cell Stem Cell doi: 10.1016/j.stem.2013.09.015 – volume: 138 start-page: 1255 year: 2010 ident: BFnature21673_CR26 publication-title: Gastroenterology doi: 10.1053/j.gastro.2010.01.005 – volume: 47 start-page: 905 year: 2013 ident: BFnature21673_CR20 publication-title: Free Radic. Res. doi: 10.3109/10715762.2013.821200 – volume: 469 start-page: 415 year: 2011 ident: BFnature21673_CR10 publication-title: Nature doi: 10.1038/nature09637 – volume: 284 start-page: 215 year: 1998 ident: BFnature21673_CR32 publication-title: J. Pharmacol. Exp. Ther. doi: 10.1016/S0022-3565(24)37225-8 – volume: 14 start-page: 537 year: 2011 ident: BFnature21673_CR4 publication-title: Cell Metab. doi: 10.1016/j.cmet.2011.08.007 – volume: 36 start-page: 765 year: 2004 ident: BFnature21673_CR28 publication-title: Free Radic. Biol. Med. doi: 10.1016/j.freeradbiomed.2003.12.019 – volume: 449 start-page: 1003 year: 2007 ident: BFnature21673_CR1 publication-title: Nature doi: 10.1038/nature06196 – volume: 99 start-page: 989 year: 2008 ident: BFnature21673_CR16 publication-title: Br. J. Cancer doi: 10.1038/sj.bjc.6604554 – volume: 9 start-page: 537 year: 2009 ident: BFnature21673_CR21 publication-title: Nat. Rev. Cancer doi: 10.1038/nrc2694 – volume: 141 start-page: 1762 year: 2011 ident: BFnature21673_CR14 publication-title: Gastroenterology doi: 10.1053/j.gastro.2011.07.050 – volume: 18 start-page: 25 year: 2016 ident: BFnature21673_CR7 publication-title: Cell Stem Cell doi: 10.1016/j.stem.2015.12.005 – volume: 461 start-page: 537 year: 2009 ident: BFnature21673_CR3 publication-title: Nature doi: 10.1038/nature08313 – volume: 43 start-page: W251 year: 2015 ident: BFnature21673_CR36 publication-title: Nucleic Acids Res. doi: 10.1093/nar/gkv380 – volume: 8 start-page: 511 year: 2011 ident: BFnature21673_CR25 publication-title: Cell Stem Cell doi: 10.1016/j.stem.2011.02.020 – volume: 1846 start-page: 617 year: 2014 ident: BFnature21673_CR15 publication-title: Biochim. Biophys. Acta – volume: 1837 start-page: 51 year: 2014 ident: BFnature21673_CR17 publication-title: Biochim. Biophys. Acta doi: 10.1016/j.bbabio.2013.07.008 – volume: 5 start-page: 553 year: 2008 ident: BFnature21673_CR19 publication-title: Nat. Methods doi: 10.1038/nmeth.1212 – volume: 149 start-page: 1006 year: 2015 ident: BFnature21673_CR30 publication-title: Gastroenterology doi: 10.1053/j.gastro.2015.06.007 – volume: 6 start-page: ra8 year: 2013 ident: BFnature21673_CR5 publication-title: Sci. Signal. doi: 10.1126/scisignal.2003638 – volume: 486 start-page: 490 year: 2012 ident: BFnature21673_CR6 publication-title: Nature doi: 10.1038/nature11163 – reference: 28356578 - Nat Rev Gastroenterol Hepatol. 2017 May;14 (5):259 – reference: 28429766 - Cell Res. 2017 Jul;27(7):851-852 |
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| Snippet | The glycolytic activity of Paneth cells provides lactate, which is required by self-renewing intestinal stem cells for oxidative metabolism to activate p38 MAP... The small intestinal epithelium self-renews every four or five days. Intestinal stem cells (Lgr5 crypt base columnar cells (CBCs)) sustain this renewal and... The small intestinal epithelium self-renews every four or five days. Intestinal stem cells (Lgr5^sup +^ crypt base columnar cells (CBCs)) sustain this renewal... The small intestinal epithelium self-renews every four or five days. Intestinal stem cells (Lgr5+ crypt base columnar cells (CBCs)) sustain this renewal and... |
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| Title | Interplay between metabolic identities in the intestinal crypt supports stem cell function |
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