Biology: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 LGR4, 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 NGN3, ATOH5 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]
REG4 Marker for enteroendocrine cells
26287467 [60]
SOX9 Required for paneth cell differentiation 17698607;[61] 17681175 [62]
SPDEF PDEF Regulates terminal differentiation of goblet cells and Paneth cells 19786015;[63] 19549527 [64]
STK11 LKB1 Required for normal differentiation of goblet and Paneth cells 19165340[65]
TGFBR2 Tgf-βRII The critical downstream target of Elf3 for enterocyte differentiation 17408644 [66]
VAV Required for enterocyte differentiation in mouse cecum and colon 19139088 [67]

References

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  2. ↑ Andreu, P.; Colnot, S.; Godard, C.; Gad, S.; Chafey, P.; Niwa-Kawakita, M.; Laurent-Puig, P.; Kahn, A. et al. (2005). "Crypt-restricted proliferation and commitment to the Paneth cell lineage following Apc loss in the mouse intestine". Development 132 (6): 1443–1451. doi:10.1242/dev.01700. PMID 15716339. 
  3. ↑ Vandussen, K. L.; Samuelson, L. C. (2010). "Mouse Atonal Homolog 1 Directs Intestinal Progenitors to Secretory Cell Rather than Absorptive Cell Fate". Developmental Biology 346 (2): 215–223. doi:10.1016/j.ydbio.2010.07.026. PMID 20691176. 
  4. ↑ Shroyer, N. F.; Helmrath, M. A.; Wang, V. Y. –C.; Antalffy, B.; Henning, S. J.; Zoghbi, H. Y. (2007). "Intestine-Specific Ablation of Mouse atonal homolog 1 (Math1) Reveals a Role in Cellular Homeostasis". Gastroenterology 132 (7): 2478–2488. doi:10.1053/j.gastro.2007.03.047. PMID 17570220. 
  5. ↑ Yang, Q.; Bermingham, N. A.; Finegold, M. J.; Zoghbi, H. Y. (2001). "Requirement of Math1 for Secretory Cell Lineage Commitment in the Mouse Intestine". Science 294 (5549): 2155–2158. doi:10.1126/science.1065718. PMID 11739954. Bibcode: 2001Sci...294.2155Y. 
  6. ↑ Muncan, V.; Heijmans, J.; Krasinski, S. D.; Büller, N. V.; Wildenberg, M. E.; Meisner, S.; Radonjic, M.; Stapleton, K. A. et al. (2011). "Blimp1 regulates the transition of neonatal to adult intestinal epithelium". Nature Communications 2: 452–. doi:10.1038/ncomms1463. PMID 21878906. Bibcode: 2011NatCo...2..452M. 
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  42. ↑ Murayama, M; Okamoto, R; Tsuchiya, K; Akiyama, J; Nakamura, T; Sakamoto, N; Kanai, T; Watanabe, M (2009). "Musashi-1 suppresses expression of Paneth cell-specific genes in human intestinal epithelial cells". J Gastroenterol 44 (3): 173–82. doi:10.1007/s00535-008-2284-4. PMID 19214660. 
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  57. ↑ Haegebarth, A; Bie, W; Yang, R; Crawford, SE; Vasioukhin, V; Fuchs, E; Tyner, AL (Jul 2006). "Protein tyrosine kinase 6 negatively regulates growth and promotes enterocyte differentiation in the small intestine". Mol Cell Biol 26 (13): 4949–57. doi:10.1128/mcb.01901-05. PMID 16782882. 
  58. ↑ 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.
  59. ↑ 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.
  60. ↑ Grün, Dominic; Lyubimova, Anna; Kester, Lennart; Wiebrands, Kay; Basak, Onur; Sasaki, Nobuo; Clevers, Hans; van Oudenaarden, Alexander (2015-09-10). "Single-cell messenger RNA sequencing reveals rare intestinal cell types". Nature 525 (7568): 251–255. doi:10.1038/nature14966. ISSN 1476-4687. PMID 26287467. Bibcode: 2015Natur.525..251G. 
  61. ↑ 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.
  62. ↑ 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.
  63. ↑ 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.
  64. ↑ Gregorieff, A; Stange, DE; Kujala, P; Begthel, H; van den Born, M; Korving, J; Peters, PJ; Clevers, H (Oct 2009). "The ets-domain transcription factor Spdef promotes maturation of goblet and paneth cells in the intestinal epithelium". Gastroenterology 137 (4): 1333–45.e1–3. doi:10.1053/j.gastro.2009.06.044. PMID 19549527. 
  65. ↑ Shorning, BY; Zabkiewicz, J; McCarthy, A; Pearson, HB; Winton, DJ; Sansom, OJ; Ashworth, A; Clarke, AR (2009). "Lkb1 deficiency alters goblet and paneth cell differentiation in the small intestine". PLOS ONE 4 (1): e4264. doi:10.1371/journal.pone.0004264. PMID 19165340. Bibcode: 2009PLoSO...4.4264S. 
  66. ↑ Flentjar, N; Chu, PY; Ng, AY; Johnstone, CN; Heath, JK; Ernst, M; Hertzog, PJ; Pritchard, MA (Apr 2007). "TGF-betaRII rescues development of small intestinal epithelial cells in Elf3-deficient mice". Gastroenterology 132 (4): 1410–9. doi:10.1053/j.gastro.2007.02.054. PMID 17408644. 
  67. ↑ 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(3):324-34.



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