List of intestinal epithelial differentiation genes
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Table of genes implicated in development and differentiation of the intestinal epithelium [1]
The table listed below is a running comprehensive list of all intestinal differential genes that have been reported in the literature. The PMID is the pubmed identification number of the papers that support the summarized information in the table corresponding to each row.
Official | Common | Function/phenotype | PMID |
---|---|---|---|
APC | Conditional deletion promotes Paneth cell differentiation at the expense of enterocyte, goblet and enteroendocrine cell differentiation. Negative regulator of beta-catenin | 15716339 [2] | |
ATOH1 | Math1, HATH1 | Commitment to secretory lineage | 20691176[3] 17570220[4] 11739954 [5] |
BLIMP1 | PRDM1 | Postnatal epithelial maturation; suckling/weaning transition | 21878906 [6] 21670299 [7] |
BMPR1A | Involved in terminal differentiation of secretory cells | 17678919 [8] | |
CBFA2T2 | Mtgr1 | Required for maintenance of secretory lineage | 16227606 [9] |
CDH1 | E-cadherin | Required for maturation/localization of Paneth and goblet cells | 21179475 [10] |
CDX1 | Cdx1 | Induced expression promoted enterocyte differentiation in IEC6 cells | 19059241 [11] 10579974 [12] |
CDX2 | Cdx2 | Involves in epithelial cell maturation as well as goblet and Paneth cell differentiation. Required for the small intestinal identity during development. In IEC-6 cells, conditional expression induced enterocyte and goblet like cells | 21081128[13] 19386267[14] 8552090 [15] |
CTNNB1 | Catenin, beta | Paneth cell differentiation. Essential for stem cell/crypt maintenance. Villus and crypt morphogenesis with Tcf3 via c-Myc | 18948094[16] 17785439[17] 17681174 [18] |
DLL1 | Functions as a cis acting element and required for goblet cell differentiation in the Notch inactive colonic epithelia. Notch ligand in intestine. Required for the maintenance of stem and progenitors | 20170633[19] 21238454 [20] | |
DLL4 | Notch ligand in intestine. Required for the maintenance of stem and progenitors | 21238454 [20] | |
ELF3 | ESE-1 | Terminal differentiation of absorptive enterocytes | 19801644 [21] |
EPHB3 | Localization of Paneth cells to crypt base | 12408869 [22] | |
FGF7 | KGF | Regulate epithelial growth and promote differentiation | 19326389 [23] |
FGFR3 | Paneth cell specification through beta-catenin/Tcf4 dependent and independent pathway. Significant reduction in Paneth cell in knockout mice. Involved in crypt development and stem cell expansion | 19407216 [24] | |
FOXA1 | HNF3A | Involved in goblet cell differentiation and enteroendocrine differentiation | 19737569 [25] |
FOXA2 | HNF3B | Involved in goblet cell differentiation and enteroendocrine differentiation | 19737569 [25] |
FZD5 | Required for Paneth cell maturation. Loss of Paneth cell genes after conditional deletion | 15778706 [26] | |
GADD45GIP1 | Crif1 | Essential Elf3 coactivator in differentiation of absorptive enterocytes | 19801644 [21] |
GATA6 | Regulates proximal-distal identity in the intestines | 21262227 [27] | |
GATA4 | Required for proximal intestinal identity | 16940177 [28] 18812176 [29] | |
GFI1 | Required for proper allocation of secretory lineage | 16230531 [30] | |
HES1 | Hes1 | Commitment to absorptive lineage | 10615124 [31] |
HNF1A | HNF1-α | Regulates terminal differentiation of enterocytes and secretory cells potentially by direct regulation of Atoh1 | 20133952 [32] 20388655 [33] |
HNF1B | HNF1-β | Regulates terminal differentiation of enterocytes and secretory cells potentially by direct regulation of Atoh1 | 20133952 [32] 20388655 [33] |
IHH | Colonocytes differentiation | 14770182 [34] | |
KLF4 | GKLF | Promotes goblet cell differentiation in colon | 21070761[35] 12015290 [36] |
LGR4 | GPR48 | Promotes Paneth cell differentiation and crypt cell proliferation. Along with LGR5, acts as the receptor for R-Spondin, a WNT co-ligand that amplifies WNT signaling | 21508962 [37] 21909076 [38] |
LGR5 | GPR49 | Premature paneth cell differentiation in fetal intestine. Intestinal stem cell marker. Along with LGR5, acts as the receptor for R-Spondin, a WNT co-ligand that amplifies WNT signaling | 19394326 [39] 21727895 [40] |
MMP9 | Negatively regulates terminal differentiation of goblet cells in colon | 17484881 [41] | |
MSI1 | Suppress paneth cell differentiation independent of Notch and Wnt signaling pathways | 19214660 [42] | |
MYBL2 | Regulates commitment of colon stem cells to differentiate | 20857481;[43] 20133952 [44] | |
MYC | Crypt loss upon conditional deletion in the adult | 16954380 [45] | |
NEUROD1 | BETA2 | Differentiation of Ngn3 enteroendocrine cells into CCK and secretin cells | 18022152;[46] 15044355 [47] |
NEUROG3 | Commitment to the enteroendocrine cell lineage | 17706959;[48] 12456641 [49] | |
NKX2-2 | Nkx2.2 | Required for a subset of enteroendocrine cells differentiation | 18022152 [46] |
NOTCH1 | Regulates absorptive cells vs secretory cells | 15959516;[50] 18274550 [51] | |
NOTCH2 | Regulates absorptive]] cells vs secretory cells | 15959516;[50] 18274550 [51] | |
NOX1 | Regulate ROS to activate Notch signaling and indirectly promote absorptive cell lineage in the colon | 20351171 [52] | |
PAX6 | Differentiation of GIP in enteroendocrine lineage | 18022152;[46] 10478839 [53] | |
PDX1 | IPF1 | Overexpression causes differentiation of immature intestinal epithelia to enteroendocrine cells. Conditional deletion alters enterocyte and enteroendocrine gene expression | 11408276;[54] 19808654 [55] |
PPARD | PPAR-δ/β | Involves in Paneth cell maturation by modulating IHH expression | 16890607 [56] |
PTK6 | BRK | Promote cell cycle exit in Wnt independent pathway and promote enterocyte differentiation | 16782882 [57] |
RB1 | pRB | Required for enterocyte terminal differentiation in small intestine | 18981186 [58] |
RBPJ | CBF1 | Conversion of progenitors and differentiated cells into goblet cells by conditional deletion | 15959515 [59] |
SOX9 | Required for paneth cell differentiation | 17698607;[60] 17681175 [61] | |
SPDEF | PDEF | Regulates terminal differentiation of goblet cells and Paneth cells | 19786015;[62] 19549527 [63] |
STK11 | LKB1 | Required for normal differentiation of goblet and Paneth cells | 19165340[64] |
TGFBR2 | Tgf-βRII | The critical downstream target of Elf3 for enterocyte differentiation | 17408644 [65] |
VAV | Required for enterocyte differentiation in mouse cecum and colon | 19139088 [66] |
References
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- ↑ Mustata RC, Van Loy T, Lefort A, Libert F, Strollo S, Vassart G, Garcia MI. Lgr4 is required for Paneth cell differentiation and maintenance of intestinal stem cells ex vivo. EMBO Rep. 2011 Jun;12(6):558-64.
- ↑ Glinka A, Dolde C, Kirsch N, Huang YL, Kazanskaya O, Ingelfinger D, Boutros M, Cruciat CM, Niehrs C. LGR4 and LGR5 are R-spondin receptors mediating Wnt/β-catenin and Wnt/PCP signalling. EMBO Rep. 2011 Sep 30;12(10):1055-61.
- ↑ Garcia MI, Ghiani M, Lefort A, Libert F, Strollo S, Vassart G. LGR5 deficiency deregulates Wnt signaling and leads to precocious Paneth cell differentiation in the fetal intestine. Dev Biol. 2009 Jul 1;331(1):58-67.
- ↑ de Lau W, Barker N, Low TY, Koo BK, Li VS, Teunissen H, Kujala P, Haegebarth A, Peters PJ, van de Wetering M, Stange DE, van Es JE, Guardavaccaro D, Schasfoort RB, Mohri Y, Nishimori K, Mohammed S, Heck AJ, Clevers H. Lgr5 homologues associate with Wnt receptors and mediate R-spondin signalling. Nature. 2011 Jul 4;476(7360):293-7.
- ↑ Garg P, Ravi A, Patel NR, Roman J, Gewirtz AT, Merlin D, Sitaraman SV. Matrix metalloproteinase-9 regulates MUC-2 expression through its effect on goblet cell differentiation. Gastroenterology. 2007 May;132(5):1877-89. Epub 2007 Feb 23.
- ↑ Murayama M, Okamoto R, Tsuchiya K, Akiyama J, Nakamura T, Sakamoto N, Kanai T, Watanabe M. Musashi-1 suppresses expression of Paneth cell-specific genes in human intestinal epithelial cells. J Gastroenterol. 2009;44(3):173-82. Epub 2009 Feb 13.
- ↑ Papetti M, Augenlicht LH. MYBL2, a link between proliferation and differentiation in maturing colon epithelial cells. J Cell Physiol. 2011 Mar;226(3):785-91
- ↑ Benoit YD, Paré F, Francoeur C, Jean D, Tremblay E, Boudreau F, Escaffit F, Beaulieu JF. Cooperation between HNF-1alpha, Cdx2, and GATA-4 in initiating an enterocytic differentiation program in a normal human intestinal epithelial progenitor cell line. Am J Physiol Gastrointest Liver Physiol. 2010 Apr;298(4):G504-17. Epub 2010 Feb 4.
- ↑ Muncan V, Sansom OJ, Tertoolen L, Phesse TJ, Begthel H, Sancho E, Cole AM, Gregorieff A, de Alboran IM, Clevers H, Clarke AR. Rapid loss of intestinal crypts upon conditional deletion of the Wnt/Tcf-4 target gene c-Myc. Mol Cell Biol. 2006 Nov;26(22):8418-26. Epub 2006 Sep 5.
- ↑ 46.0 46.1 46.2 Desai S, Loomis Z, Pugh-Bernard A, Schrunk J, Doyle MJ, Minic A, McCoy E, Sussel L. Nkx2.2 regulates cell fate choice in the enteroendocrine cell lineages of the intestine. Dev Biol. 2008 Jan 1;313(1):58-66. Epub 2007 Oct 3.
- ↑ Schonhoff SE, Giel-Moloney M, Leiter AB. Minireview: Development and differentiation of gut endocrine cells. Endocrinology. 2004 Jun;145(6):2639-44. Epub 2004 Mar 24.
- ↑ López-Díaz L, Jain RN, Keeley TM, VanDussen KL, Brunkan CS, Gumucio DL, Samuelson LC. Intestinal Neurogenin 3 directs differentiation of a bipotential secretory progenitor to endocrine cell rather than goblet cell fate. Dev Biol. 2007 Sep 15;309(2):298-305. Epub 2007 Jul 24.
- ↑ Jenny M, Uhl C, Roche C, Duluc I, Guillermin V, Guillemot F, Jensen J, Kedinger M, Gradwohl G. Neurogenin3 is differentially required for endocrine cell fate specification in the intestinal and gastric epithelium. EMBO J. 2002 Dec 2;21(23):6338-47.
- ↑ 50.0 50.1 Fre S, Huyghe M, Mourikis P, Robine S, Louvard D, Artavanis-Tsakonas S. Notch signals control the fate of immature progenitor cells in the intestine. Nature. 2005 Jun 16;435(7044):964-8.
- ↑ 51.0 51.1 Riccio O, van Gijn ME, Bezdek AC, Pellegrinet L, van Es JH, Zimber-Strobl U, Strobl LJ, Honjo T, Clevers H, Radtke F. Loss of intestinal crypt progenitor cells owing to inactivation of both Notch1 and Notch2 is accompanied by derepression of CDK inhibitors p27Kip1 and p57Kip2. EMBO Rep. 2008 Apr;9(4):377-83. Epub 2008 Feb 15.
- ↑ Coant N, Ben Mkaddem S, Pedruzzi E, Guichard C, Tréton X, Ducroc R, Freund JN, Cazals-Hatem D, Bouhnik Y, Woerther PL, Skurnik D, Grodet A, Fay M, Biard D, Lesuffleur T, Deffert C, Moreau R, Groyer A, Krause KH, Daniel F, Ogier-Denis E. NADPH oxidase 1 modulates WNT and NOTCH1 signaling to control the fate of proliferative progenitor cells in the colon. Mol Cell Biol. 2010 Jun;30(11):2636-50. Epub 2010 Mar 29.
- ↑ Hill ME, Asa SL, Drucker DJ. Essential requirement for Pax6 in control of enteroendocrine proglucagon gene transcription. Mol Endocrinol. 1999 Sep;13(9):1474-86.
- ↑ Yamada S, Kojima H, Fujimiya M, Nakamura T, Kashiwagi A, Kikkawa R. Differentiation of immature enterocytes into enteroendocrine cells by Pdx1 overexpression. Am J Physiol Gastrointest Liver Physiol. 2001 Jul;281(1):G229-36.
- ↑ Chen C, Fang R, Davis C, Maravelias C, Sibley E. Pdx1 inactivation restricted to the intestinal epithelium in mice alters duodenal gene expression in enterocytes and enteroendocrine cells. Am J Physiol Gastrointest Liver Physiol. 2009 Dec;297(6):G1126-37. Epub 2009 Oct 1.
- ↑ Varnat F, Heggeler BB, Grisel P, Boucard N, Corthésy-Theulaz I, Wahli W, Desvergne B. PPARbeta/delta regulates paneth cell differentiation via controlling the hedgehog signaling pathway. Gastroenterology. 2006 Aug;131(2):538-53.
- ↑ Haegebarth A, Bie W, Yang R, Crawford SE, Vasioukhin V, Fuchs E, Tyner AL. Protein tyrosine kinase 6 negatively regulates growth and promotes enterocyte differentiation in the small intestine. Mol Cell Biol. 2006 Jul;26(13):4949-57.
- ↑ Guo J, Longshore S, Nair R, Warner BW. Retinoblastoma protein (pRb), but not p107 or p130, is required for maintenance of enterocyte quiescence and differentiation in small intestine. J Biol Chem. 2009 Jan 2;284(1):134-40. Epub 2008 Nov 3.
- ↑ van Es JH, van Gijn ME, Riccio O, van den Born M, Vooijs M, Begthel H, Cozijnsen M, Robine S, Winton DJ, Radtke F, Clevers H. Notch/gamma-secretase inhibition turns proliferative cells in intestinal crypts and adenomas into goblet cells. Nature. 2005 Jun 16;435(7044):959-63.
- ↑ Bastide P, Darido C, Pannequin J, Kist R, Robine S, Marty-Double C, Bibeau F, Scherer G, Joubert D, Hollande F, Blache P, Jay P. Sox9 regulates cell proliferation and is required for Paneth cell differentiation in the intestinal epithelium. J Cell Biol. 2007 Aug 13;178(4):635-48.
- ↑ Mori-Akiyama Y, van den Born M, van Es JH, Hamilton SR, Adams HP, Zhang J, Clevers H, de Crombrugghe B. SOX9 is required for the differentiation of paneth cells in the intestinal epithelium. Gastroenterology. 2007 Aug;133(2):539-46. Epub 2007 May 21.
- ↑ Noah TK, Kazanjian A, Whitsett J, Shroyer NF. SAM pointed domain ETS factor (SPDEF) regulates terminal differentiation and maturation of intestinal goblet cells. Exp Cell Res. 2010 Feb 1;316(3):452-65. Epub 2009 Sep 26.
- ↑ Gregorieff A, Stange DE, Kujala P, Begthel H, van den Born M, Korving J, Peters PJ, Clevers H. The ets-domain transcription factor Spdef promotes maturation of goblet and paneth cells in the intestinal epithelium. Gastroenterology. 2009 Oct;137(4):1333-45.e1-3. Epub 2009 Jun 21.
- ↑ Shorning BY, Zabkiewicz J, McCarthy A, Pearson HB, Winton DJ, Sansom OJ, Ashworth A, Clarke AR. Lkb1 deficiency alters goblet and paneth cell differentiation in the small intestine. PLoS One. 2009;4(1):e4264. Epub 2009 Jan 23.
- ↑ Flentjar N, Chu PY, Ng AY, Johnstone CN, Heath JK, Ernst M, Hertzog PJ, Pritchard MA. TGF-betaRII rescues development of small intestinal epithelial cells in Elf3-deficient mice. Gastroenterology. 2007 Apr;132(4):1410-9. Epub 2007 Feb 25.
- ↑ Liu JY, Seno H, Miletic AV, Mills JC, Swat W, Stappenbeck TS. Vav proteins are necessary for correct differentiation of mouse cecal and colonic enterocytes. J Cell Sci. 2009 Feb 1;122(Pt 3):324-34. Epub 2009 Jan 12.