List of intestinal epithelial differentiation genes

Last updated

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.

OfficialCommonFunction/phenotypePMID
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, HATH1Commitment to secretory lineage20691176 [3] 17570220 [4] 11739954 [5]
BLIMP1 PRDM1Postnatal epithelial maturation; suckling/weaning transition21878906 [6] 21670299 [7]
BMPR1A Involved in terminal differentiation of secretory cells17678919 [8]
CBFA2T2 Mtgr1Required for maintenance of secretory lineage16227606 [9]
CDH1 E-cadherinRequired for maturation/localization of Paneth and goblet cells21179475 [10]
CDX1 Cdx1Induced expression promoted enterocyte differentiation in IEC6 cells19059241 [11] 10579974 [12]
CDX2 Cdx2Involves 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 cells21081128 [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-Myc18948094 [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-1Terminal differentiation of absorptive enterocytes 19801644 [21]
EPHB3 Localization of Paneth cells to crypt base12408869 [22]
FGF7 KGFRegulate 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 expansion19407216 [24]
FOXA1 HNF3AInvolved in goblet cell differentiation and enteroendocrine differentiation 19737569 [25]
FOXA2 HNF3BInvolved in goblet cell differentiation and enteroendocrine differentiation 19737569 [25]
FZD5 Required for Paneth cell maturation. Loss of Paneth cell genes after conditional deletion15778706 [26]
GADD45GIP1 Crif1Essential Elf3 coactivator in differentiation of absorptive enterocytes 19801644 [21]
GATA6 Regulates proximal-distal identity in the intestines 21262227 [27]
GATA4 Required for proximal intestinal identity16940177 [28] 18812176 [29]
GFI1 Required for proper allocation of secretory lineage16230531 [30]
HES1 Hes1Commitment to absorptive lineage10615124 [31]
HNF1A HNF1-αRegulates terminal differentiation of enterocytes and secretory cells potentially by direct regulation of Atoh120133952 [32] 20388655 [33]
HNF1B HNF1-βRegulates terminal differentiation of enterocytes and secretory cells potentially by direct regulation of Atoh120133952 [32] 20388655 [33]
IHH Colonocytes differentiation 14770182 [34]
KLF4 GKLFPromotes goblet cell differentiation in colon 21070761 [35] 12015290 [36]
LGR4 GPR48Promotes Paneth cell differentiation and crypt cell proliferation. Along with LGR5, acts as the receptor for R-Spondin, a WNT co-ligand that amplifies WNT signaling21508962 [37] 21909076 [38]
LGR5 GPR49Premature 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 signaling19394326 [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 pathways19214660 [42]
MYBL2 Regulates commitment of colon stem cells to differentiate 20857481; [43] 20133952 [44]
MYC Crypt loss upon conditional deletion in the adult16954380 [45]
NEUROD1 BETA2 Differentiation of Ngn3 enteroendocrine cells into CCK and secretin cells18022152; [46] 15044355 [47]
NEUROG3 NGN3, ATOH5Commitment to the enteroendocrine cell lineage17706959; [48] 12456641 [49]
NKX2-2 Nkx2.2Required for a subset of enteroendocrine cells differentiation 18022152 [46]
NOTCH1 Regulates absorptive cells vs secretory cells15959516; [50] 18274550 [51]
NOTCH2 Regulates absorptive cells vs secretory cells15959516; [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 lineage18022152; [46] 10478839 [53]
PDX1 IPF1Overexpression causes differentiation of immature intestinal epithelia to enteroendocrine cells. Conditional deletion alters enterocyte and enteroendocrine gene expression11408276; [54] 19808654 [55]
PPARD PPAR-δ/βInvolves in Paneth cell maturation by modulating IHH expression16890607 [56]
PTK6 BRKPromote cell cycle exit in Wnt independent pathway and promote enterocyte differentiation 16782882 [57]
RB1 pRBRequired for enterocyte terminal differentiation in small intestine18981186 [58]
RBPJ CBF1Conversion of progenitors and differentiated cells into goblet cells by conditional deletion15959515 [59]
REG4 Marker for enteroendocrine cells
26287467 [60]
SOX9 Required for paneth cell differentiation 17698607; [61] 17681175 [62]
SPDEF PDEFRegulates terminal differentiation of goblet cells and Paneth cells19786015; [63] 19549527 [64]
STK11 LKB1Required for normal differentiation of goblet and Paneth cells19165340 [65]
TGFBR2 Tgf-βRIIThe critical downstream target of Elf3 for enterocyte differentiation 17408644 [66]
VAV Required for enterocyte differentiation in mouse cecum and colon 19139088 [67]

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<span class="mw-page-title-main">Barrett's esophagus</span> Medical condition

Barrett's esophagus is a condition in which there is an abnormal (metaplastic) change in the mucosal cells lining the lower portion of the esophagus, from stratified squamous epithelium to simple columnar epithelium with interspersed goblet cells that are normally present only in the small intestine and large intestine. This change is considered to be a premalignant condition because it is associated with a high incidence of further transition to esophageal adenocarcinoma, an often-deadly cancer.

<span class="mw-page-title-main">Peyer's patch</span> Lymphatic tissue in the lower small intestine

Peyer's patches are organized lymphoid follicles, named after the 17th-century Swiss anatomist Johann Conrad Peyer. They are an important part of gut associated lymphoid tissue usually found in humans in the lowest portion of the small intestine, mainly in the distal jejunum and the ileum, but also could be detected in the duodenum.

<span class="mw-page-title-main">Goblet cell</span> Epithelial cells that secrete mucins

Goblet cells are simple columnar epithelial cells that secrete gel-forming mucins, like mucin 5AC. The goblet cells mainly use the merocrine method of secretion, secreting vesicles into a duct, but may use apocrine methods, budding off their secretions, when under stress. The term goblet refers to the cell's goblet-like shape. The apical portion is shaped like a cup, as it is distended by abundant mucus laden granules; its basal portion lacks these granules and is shaped like a stem.

<span class="mw-page-title-main">Caco-2</span>

Caco-2 is an immortalized cell line of human colorectal adenocarcinoma cells. It is primarily used as a model of the intestinal epithelial barrier. In culture, Caco-2 cells spontaneously differentiate into a heterogeneous mixture of intestinal epithelial cells. It was developed in 1977 by Jorgen Fogh at the Sloan-Kettering Institute for Cancer Research.

<span class="mw-page-title-main">Paneth cell</span> Anti-microbial epithelial cell of the small intestine

Paneth cells are cells in the small intestine epithelium, alongside goblet cells, enterocytes, and enteroendocrine cells. Some can also be found in the cecum and appendix. They are located below the intestinal stem cells in the intestinal glands and the large eosinophilic refractile granules that occupy most of their cytoplasm.

<span class="mw-page-title-main">Intestinal gland</span> Gland between the intestinal villi that produces new cells

In histology, an intestinal gland is a gland found in between villi in the intestinal epithelium lining of the small intestine and large intestine. The glands and intestinal villi are covered by epithelium, which contains multiple types of cells: enterocytes, goblet cells, enteroendocrine cells, cup cells, tuft cells, and at the base of the gland, Paneth cells and stem cells.

Microfold cells are found in the gut-associated lymphoid tissue (GALT) of the Peyer's patches in the small intestine, and in the mucosa-associated lymphoid tissue (MALT) of other parts of the gastrointestinal tract. These cells are known to initiate mucosal immunity responses on the apical membrane of the M cells and allow for transport of microbes and particles across the epithelial cell layer from the gut lumen to the lamina propria where interactions with immune cells can take place.

<span class="mw-page-title-main">CDX2</span> Protein-coding gene in the species Homo sapiens

Homeobox protein CDX-2 is a protein that in humans is encoded by the CDX2 gene. The CDX2 protein is a homeobox transcription factor expressed in the nuclei of intestinal epithelial cells, playing an essential role in the development and function of the digestive system. CDX2 part of the ParaHox gene cluster, a group of three highly conserved developmental genes present in most vertebrate species. Together with CDX1 and CDX4, CDX2 is one of three caudal-related genes in the human genome.

<span class="mw-page-title-main">KLF4</span> Protein-coding gene in the species Homo sapiens

Kruppel-like factor 4 is a member of the KLF family of zinc finger transcription factors, which belongs to the relatively large family of SP1-like transcription factors. KLF4 is involved in the regulation of proliferation, differentiation, apoptosis and somatic cell reprogramming. Evidence also suggests that KLF4 is a tumor suppressor in certain cancers, including colorectal cancer. It has three C2H2-zinc fingers at its carboxyl terminus that are closely related to another KLF, KLF2. It has two nuclear localization sequences that signals it to localize to the nucleus. In embryonic stem cells (ESCs), KLF4 has been demonstrated to be a good indicator of stem-like capacity. It is suggested that the same is true in mesenchymal stem cells (MSCs).

<span class="mw-page-title-main">LGR5</span> Protein-coding gene in humans

Leucine-rich repeat-containing G-protein coupled receptor 5 (LGR5) also known as G-protein coupled receptor 49 (GPR49) or G-protein coupled receptor 67 (GPR67) is a protein that in humans is encoded by the LGR5 gene. It is a member of GPCR class A receptor proteins. R-spondin proteins are the biological ligands of LGR5. LGR5 is expressed across a diverse range of tissue such as in the muscle, placenta, spinal cord and brain and particularly as a biomarker of adult stem cells in certain tissues.

<span class="mw-page-title-main">Trefoil factor 3</span> Protein-coding gene in the species Homo sapiens

Trefoil factor 3 is a protein that in humans is encoded by the TFF3 gene.

<span class="mw-page-title-main">ATOH1</span> Protein-coding gene in the species Homo sapiens

Protein atonal homolog 1 is a protein that in humans is encoded by the ATOH1 gene.

<span class="mw-page-title-main">Intestinal epithelium</span> Single-cell layer lining the intestines

The intestinal epithelium is the single cell layer that form the luminal surface (lining) of both the small and large intestine (colon) of the gastrointestinal tract. Composed of simple columnar epithelial cells, it serves two main functions: absorbing useful substances into the body and restricting the entry of harmful substances. As part of its protective role, the intestinal epithelium forms an important component of the intestinal mucosal barrier. Certain diseases and conditions are caused by functional defects in the intestinal epithelium. On the other hand, various diseases and conditions can lead to its dysfunction which, in turn, can lead to further complications.

Congenital tufting enteropathy is an inherited disorder of the small intestine that presents with intractable diarrhea in young children.

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Tetratricopeptide repeat domain 7A (TTC7A) is a protein that in humans is encoded by the TTC7A gene.

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References

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