[1] WANG Y L,GUNASEKARA D B,REED M I,et al.A microengineered collagen scaffold for generating a polarized crypt-villus architecture of human small intestinal epithelium[J].Biomaterials,2017,128:44-55.
[2] YAN K S,JANDA C Y,CHANG J L,et al.Non-equivalence of Wnt and R-spondin ligands during Lgr5
+ intestinal stem-cell self-renewal[J].Nature,2017,545(7653):238-242.

[3] OGAKI S,SHIRAKI N,KUME K,et al.Wnt and Notch signals guide embryonic stem cell differentiation into the intestinal lineages[J].Stem Cells,2013,31(6):1086-1096.

[4] DEMITRACK E S,SAMUELSON L C.Notch regulation of gastrointestinal stem cells[J].The Journal of Physiology,2016,594(17):4791-4803.

[5] QI Z,LI Y H,ZHAO B,et al.BMP restricts stemness of intestinal Lgr5
+ stem cells by directly suppressing their signature genes[J].Nature Communications,2017,8:13824.
[6] BARTFELD S,CLEVERS H.Stem cell-derived organoids and their application for medical research and patient treatment[J].Journal of Molecular Medicine,2017,95(7):729-738.

[7] ZOU L J,XIONG X,WANG X C,et al.Current advances in renewal mechanisms of intestinal epithelial cells along the crypt-villus axis[J].Scientia Sinica Vitae,2017,47(2):190-200.

[8] LI X G,WANG Z,CHEN R Q,et al.LGR5 and BMI1 increase pig intestinal epithelial cell proliferation by stimulating Wnt/β-catenin signaling[J].International Journal of Molecular Sciences,2018,19(4):E1036.
[9] YAN K S,CHIA L A,LI X N,et al.The intestinal stem cell markers Bmi1 and Lgr5 identify two functionally distinct populations[J].Proceedings of the National Academy of Sciences of the United States of America,2012,109(2):466-471.

[10] LI C M,YAN H C,FU H L,et al.Molecular cloning,sequence analysis,and function of the intestinal epithelial stem cell marker
Bmi1 in pig intestinal epithelial cells[J].Journal of Animal Science,2014,92(1):85-94.

[11] ZHOU J Y,HUANG D G,QIN Y C,et al.mTORC1 signaling activation increases intestinal stem cell activity and promotes epithelial cell proliferation[J].Journal of Cellular Physiology,2019,doi:10.1002/jcp.28542.
[12] 冯涛,嵇武.肠道干细胞标记物的研究进展[J].肠外与肠内营养,2014,21(2):119-122.
[13] BOGUNOVIC M,DAVÉ S H,TILSTRA J S,et al.Enteroendocrine cells express functional Toll-like receptors[J].American Journal of Physiology Gastrointestinal & Liver Physiology,2007,292(6):G1770-G1783.
[14] SANCHO E,BATLLE E,CLEVERS H.Live and let die in the intestinal epithelium[J].Current Opinion in Cell Biology,2003,15(6):763-770.

[15] OKUMURA R,TAKEDA K.Roles of intestinal epithelial cells in the maintenance of gut homeostasis[J].Experimental & Molecular Medicine,2017,49(5):e338.
[16] VAN AMERONGEN R,MIKELS A,NUSSE R.Alternative wnt signaling is initiated by distinct receptors[J].Science Signaling,2008,1(35):re9.
[17] BARKER N.Adult intestinal stem cells:critical drivers of epithelial homeostasis and regeneration[J].Nature Reviews Molecular Cell Biology,2014,15(1):19-33.

[18] CLEVERS H,NUSSE R.Wnt/β-catenin signaling and disease[J].Cell,2012,149(6):1192-1205.

[19] AOKI R,SHOSHKES-CARMEL M,GAO N,et al.
Foxl1-expressing mesenchymal cells constitute the intestinal stem cell niche[J].Cellular and Molecular Gastroenterology and Hepatology,2016,2(2):175-188.

[20] SECRETO F J,HOEPPNER L H,WESTENDORF J J.Wnt signaling during fracture repair[J].Current Osteoporosis Reports,2009,7(2):64-69.

[21] CAMAC K S,THOMPSON F M,CUMMINS A G.Activation of β-catenin in the stem cell region of crypts during growth of the small intestine in infant rats[J].Digestive Diseases and Sciences,2007,52(5):1242-1246.

[22] SPIEGELMAN V S,SLAGA T J,PAGANO M,et al.Wnt/β-catenin signaling induces the expression and activity of βTrCP ubiquitin ligase receptor[J].Molecular Cell,2000,5(5):877-882.

[23] SAWA M,MASUDA M,YAMADA T.Targeting the Wnt signaling pathway in colorectal cancer[J].Expert Opinion on Therapeutic Targets,2016,20(4):419-429.

[24] KOCH S.Extrinsic control of Wnt signaling in the intestine[J].Differentiation,2017,97:1-8.
[25] KRIZ V,KORINEK V.Wnt,RSPO and Hippo signalling in the intestine and intestinal stem cells[J].Genes,2018,9(1):E20.
[26] HAO H X,XIE Y,ZHANG Y,et al.ZNRF3 promotes Wnt receptor turnover in an R-spondin-sensitive manner[J].Nature,2012,485(7397):195-200.

[27] 王冬立.R-spondin家族蛋白与其受体相互作用的结构生物学研究[D].博士学位论文.北京:清华大学,2014:79-86.
[28] CRUCIAT C M,NIEHRS C.Secreted and transmembrane Wnt inhibitors and activators[J].Cold Spring Harbor Perspectives in Biology,2013,5(3):a015081.
[29] KAWANO Y,KYPTA R.Secreted antagonists of the Wnt signalling pathway[J].Journal of Cell Science,2003,116(13):2627-2634
[30] MAH A T,YAN K S,KUO C J.Wnt pathway regulation of intestinal stem cells[J].The Journal of Physiology,2016,594(17):4837-4847.

[31] KRAUSOVA M,KORINEK V.Wnt signaling in adult intestinal stem cells and cancer[J].Cellular Signalling,2014,26(3):570-579.

[32] MACDONALD B T,TAMAI K,HE X.Wnt/β-catenin signaling:components,mechanisms,and diseases[J].Developmental Cell,2009,17(1):9-26.

[33] BAARSMA H A,KÖNIGSHOFF M,GOSENS R.The Wnt signaling pathway from ligand secretion to gene transcription:molecular mechanisms and pharmacological targets[J].Pharmacology & Therapeutics,2013,138(1):66-83.

[34] GREICIUS G,KABIRI Z,SIGMUNDSSON K,et al.PDGFRα
+ pericryptal stromal cells are the critical source of Wnts and RSPO3 for murine intestinal stem cells
in vivo[J].Proceedings of the National Academy of Sciences of the United States of America,2018,115(14):E3173-E3181.
[35] DANN C E,HSIEH J C,RATTNER A,et al.Insights into Wnt binding and signalling from the structures of two Frizzled cysteine-rich domains[J].Nature,2001,412(6842):86-90.

[36] POVELONES M,NUSSE R.The role of the cysteine-rich domain of Frizzled in Wingless-Armadillo signaling[J].The EMBO Journal,2005,24(19):3493-3503.

[37] FAN H B,ZHAI Z Y,LI X G,et al.CDX2 stimulates the proliferation of porcine intestinal epithelial cells by activating the mtorc1 and Wnt/β-catenin signaling pathways[J].International Journal of Molecular Sciences,2017,18(11):2447.
[38] KABIRI Z,GREICIUS G,MADAN B,et al.Stroma provides an intestinal stem cell niche in the absence of epithelial Wnts[J].Development,2014,141(11):2206-2215.

[39] ZOU W Y,BLUTT S E,CRAWFORD S E,et al.Human intestinal enteroids:new models to study gastrointestinal virus infections[J].Methods in Molecular Biology,2017,doi:10.1007/7651_2017_1.
[40] ASCIOLLA J J,MIELE M M,HENDRICKSON R C,et al.An
in vitro fatty acylation assay reveals a mechanism for Wnt recognition by the acyltransferase
Porcupine[J].Journal of Biological Chemistry,2017,292(33):13507-13513.

[41] VALENTA T,DEGIRMENCI B,MOOR A E,et al.Wnt ligands secreted by subepithelial mesenchymal cells are essential for the survival of intestinal stem cells and gut homeostasis[J].Cell Reports,2016,15(5):911-918.

[42] NALAPAREDDY K,NATTAMAI K J,KUMAR R S,et al.Canonical Wnt signaling ameliorates aging of intestinal stem cells[J].Cell Reports,2017,18(11):2608-2621.

[43] CHEUNG R,KELLY J,MACLEOD R J.Regulation of villin by Wnt5a/Ror2 signaling in human intestinal cells[J].Frontiers in Physiology,2011,2:58.
[44] ROMAN S,KATRINA A.Mechanisms of stem cell maintenance and cell differentiation in the intestinal epithelium[D].Ph.D.Thesis.Cambridge:Harvard University,2015.
[45] DEGIRMENCI B,HAUSMANN G,VALENTA T,et al.Wnt ligands as a part of the stem cell niche in the intestine and the liver[J].Progress in Molecular Biology and Translational Science,2018,153:1-19.
[46] IRELAND H,KEMP R,HOUGHTON C,et al.Inducible Cre-mediated control of gene expression in the murine gastrointestinal tract:effect of loss of β-catenin[J].Gastroenterology,2004,126(5):1236-1246.

[47] YOUNG M A.The effects of aberrant Wnt signalling on the murine intestinal stem cell compartment[D].Ph.D.Thesis.Wales:Cardiff University,2013:2-17.
[48] GEHART H,CLEVERS H.Tales from the crypt:new insights into intestinal stem cells[J].Nature Reviews Gastroenterology & Hepatology,2018,16(1):19-34.
[49] JANECKOVA L,FAFILEK B,KRAUSOVA M,et al.Wnt signaling inhibition deprives small intestinal stem cells of clonogenic capacity[J].Genesis,2016,54(3):101-114.

[50] SANCHO E,BATLLE E,CLEVERS H.Signaling pathways in intestinal development and cancer[J].Annual Review of Cell and Developmental Biology,2004,20:695-723.
[51] PETERSON L W,ARTIS D.Intestinal epithelial cells:regulators of barrier function and immune homeostasis[J].Nature Reviews Immunology,2014,14(3):141-153.

[52] LEE C,MINICH A,LI B,et al.Influence of stress factors on intestinal epithelial injury and regeneration[J].Pediatric Surgery International,2018,34(2):155-160.

[53] LIU X Y,WU S P,XIA Y L,et al.Wingless homolog Wnt11 suppresses bacterial invasion and inflammation in intestinal epithelial cells[J].American Journal of Physiology Gastrointestinal & Liver Physiology,2011,301(6):G992-G1003.
[54] LABED S A,WANI K A,JAGADEESAN S,et al.Intestinal epithelial Wnt signaling mediates acetylcholine-triggered host defense against infection[J].Immunity,2018,48(5):963-978.e3.

[55] HOECK J D,BIEHS B,KURTOVA A V,et al.Stem cell plasticity enables hair regeneration following Lgr5
+ cell loss[J].Nature Cell Biology,2017,19(6):666-676.

[56] SAHA S,ARANDA E,HAYAKAWA Y,et al.Macrophage-derived extracellular vesicle-packaged Wnts rescue intestinal stem cells and enhance survival after radiation injury[J].Nature Communications,2016,7:13096.
[57] GONG W,GUO M Z,HAN Z B,et al.Mesenchymal stem cells stimulate intestinal stem cells to repair radiation-induced intestinal injury[J].Cell Death & Disease,2016,7(9):e2387.
[58] CHEN W,JU S W,LU T,et al.Directional delivery of RSPO1 by mesenchymal stem cells ameliorates radiation-induced intestinal injury[J].Cytokine,2017,95:27-34.
[59] NAM M O,HAHN S,JEE J H,et al.Effects of a small molecule R-spondin-1 substitute RS-246204 on a mouse intestinal organoid culture[J].Oncotarget,2018,9(5):6356-6368.
[60] LI X G,ZHU M,CHEN M X,et al.Acute exposure to deoxynivalenol inhibits porcine enteroid activity via suppression of the Wnt/β-catenin pathway[J].Toxicology Letters,2019,305:19-31.
[61] 周加义.Wnt/β-catenin通路介导热暴露抑制猪肠上皮细胞增殖分化和干细胞扩增的研究[D].硕士学位论文.广州:华南农业大学,2018:20-30.
[62] 黄登桂.猪大肠杆菌耐热肠毒素损伤肠上皮完整性的机制研究[D].硕士学位论文.广州:华南农业大学,2019:23-34.