Gene | Function | References |
---|---|---|
nanog (Nanog homeobox) | Critical for early embryogenesis and for ESC pluripotency | |
oct4 (POU domain, class 5, transcription factor 1 | ||
sox2 (SRY (sex determining region Y)-box 2 | ||
foxa2 (forkhead box A2) | Necessary for proper endoderm formation and pdx1 expression. Also required for regulated insulin secretion in mature β-cells—regulates the expression of important genes for glucose sensing in pancreatic β-cells and glucose homeostasis | |
cxcr4 (chemokine (C-X-C motif) receptor 4) | Required for proper β cells generation – it is a key marker of definitive endoderm, controlling cells migration during gastrulation | |
sox17 (SRY (sex determining region Y)-box 17 | Controls segregation of liver, biliary system, and pancreas; regulates insulin trafficking and secretion in β-cells | |
nkx6.1 (NK6 homeobox 1) | Directly targeted genes involved in insulin biosynthesis (Slc30a8 and Ero1lb), glucose transporter 2 (Glut2), and glucose metabolism | [96] |
pdx1 (pancreatic and duodenal homeobox 1 | Mainly involved in glucose-dependent regulation of insulin gene expression. Also necessary for the activation of several genes, including insulin, somatostatin, glucokinase, islet amyloid polypeptide and GLUT2 | |
ptf1a (pancreas associated transcription factor 1a | Required for exocrine cell formation—activates an acinar cell genes repertoire. Has a complex set of interactions with Notch downstream intercellular mediators to regulate target patterning genes and acinar-specific genes | |
sox9 (SRY-box transcription factor 9) | Necessary for regulation of pancreatic specification, differentiation and duct morphology | |
Cg (Chromogranin) A | Constitute the regulated pathway of protein hormone secretion including all four pancreatic peptide hormones and gastrin. It is involved in the generation of secretory granules and is considered a pan-endocrine marker | |
ngn3 (neurogenin 3) | Endocrine formation key regulator—induces the expression of endocrine genes such as neuroD1, nkx2.2, nkx6.1, pax4, pax6 and isl1 | |
neuroD1 (neurogenic differentiation 1) | Involved in islet growth, proliferation and endocrine differentiation in pancreatic progenitors. Activates IA1 (Insulin Associated 1), a zinc finger protein that appears to be important in executing the endocrine differentiation process. Can activate the pax6 gene | |
nkx2.2 (NK2 homeobox 2) | Necessary for β-cell precursors to express nkx6.1 and ins. Also binds to and activates mafa | |
pax4 (paired box gene 4) | Directs formation of β and δ cells. Acts as a transcriptional repressor, being especially effective for ghrelin expression and pax6-mediated glucagon expression | |
ins (insulin) | Provides instructions for producing the insulin hormone | [125] |
mafa (v-maf musculoaponeurotic fibrosarcoma oncogene family, protein A) | Controls and activates insulin gene expression | |
mafb (v-maf musculoaponeurotic fibrosarcoma oncogene family, protein B) | Appears to be a key regulator of α- and β-cell maturation, since Mafb binds to and activates the mafa gene, causing a transition from mafb to mafa expression in insulin + cells as they transition from immature to mature β cells | [128] |
Glut2 / SLC2A2 (solute carrier family 2 member 2) | An integral plasma membrane glycoprotein of islet β-cells that mediates facilitated bidirectional glucose transport | [129] |