The role of GLI protein family in trophoblast cell differentiation

GLI proteini sudionici su evolucijski konzerviranog Hedgehog (Hh) signalnog puta koji tijekom embrionalnog razvoja ima ključnu ulogu u prolifereciji i diferencijaciji stanica te morfogenezi određenih tkiva i organa. Hh signalni put aktivira se vezanjem Hh liganada za PTCH transmembranski receptor pri čemu se aktivira SMO te dolazi do povećane aktivnosti GLI transkripcijskih faktora koji potiču transkripciju ciljnih gena. Kod ljudi su pronađene tri izoforme GLI proteina GLI1, GLI2 i GLI3 koji zbog razlika u građi nemaju jednaku funkciju. GLI proteini sudjeluju u diferencijaciji trofoblasta tijekom razvoja posteljice pri čemu se matične pluripotentne stanica trofoblasta diferenciraju u stanice citotrofoblasta koje su ključne u nastanku dvaju slojeva posteljice, nemigrirajućeg viloznog trofoblasta građenog od stanica sinciciotrofoblasta i invazivnog ekstraviloznog trofoblasta građenog od stanica citotrofoblasta. Ova dva sloja posteljice razlikuju se po svojim funkcijama. Ako dođe do poremećene aktivacije Hh signalnog puta i ometanja normalne signalne kaskade pa samim time i aberantne ekspresije GLI proteina, može doći do poremećaja u diferencijaciji trofoblasta što vodi razvoju raznih bolesti kao što su hidatiformna mola, invazivna mola, koriokarcinom, trofoblastični tumor ležišta posteljice i epiteloidni trofoblastični tumor. Navedene bolesti obilježene su abnormalnom proliferacijom trofoblasta te zajedno čine skup patoloških stanja posteljice zvan gestacijska trofoblastična bolest. Povezanost aberantne ekspresije GLI proteina s razvojem bolesti ukazuje na važnost pravilne regulacije ovih transkripcijskih faktora tijekom diferencijacije trofoblasta i normalnog razvoja posteljice.GLI proteins are participants of the evolutionary conserved Hedgehog (Hh) signaling pathway, which plays a key role in the proliferation and differentiation of cells and morphogenesis of particular tissues and organs. Hh signaling pathways activate by binding of Hh ligands to the PTCH transmembranous receptor. In this process SMO activates and that leads to an increased activity of the GLI transcription factors, which support the transcription of target genes. There are three isoforms of the GLI proteins in people GLI1, GLI2, GLI3, which do not have the same function because of the difference in structure. GLI proteins participate in the differentiation of trophoblasts in the development of the placenta. The stem cells of the trophoblast differentiate into cytotrophoblast cells (which play a key role in the creation of the two layers of the placenta), non-migratory villous trophoblast (built of syntitiotrophoblast cells) and an invasive extravillous trophoblast (built of cytotrophoblast cells). These two layers of the placenta differentiate in functions. If a disrupted activation of the Hh signaling pathway and disruption of a normal signaling cascade (and therefore even an aberrant expression of GLI proteins) occurs, a disruption in differentiation of the trophoblasts that leads to different diseases (such as hydatidiform mole, invasive mole, choriocarcinoma, placental site trophoblastic tumour and epitheloid trophoblastic tumour) may occur. The mentioned diseases are characterised by abnormal proliferation of trophoblasts and together make up a group of pathological conditions known as gestational trophoblastic diseases. The connection of the aberrant expression of the GLI proteins along with the development of diseases shows the importance of a standard regulation of transcription factors during the dfferentiation of trophoblasts and a normal development of the placenta

The role of GLI protein family in trophoblast cell differentiation

GLI proteini sudionici su evolucijski konzerviranog Hedgehog (Hh) signalnog puta koji tijekom embrionalnog razvoja ima ključnu ulogu u prolifereciji i diferencijaciji stanica te morfogenezi određenih tkiva i organa. Hh signalni put aktivira se vezanjem Hh liganada za PTCH transmembranski receptor pri čemu se aktivira SMO te dolazi do povećane aktivnosti GLI transkripcijskih faktora koji potiču transkripciju ciljnih gena. Kod ljudi su pronađene tri izoforme GLI proteina GLI1, GLI2 i GLI3 koji zbog razlika u građi nemaju jednaku funkciju. GLI proteini sudjeluju u diferencijaciji trofoblasta tijekom razvoja posteljice pri čemu se matične pluripotentne stanica trofoblasta diferenciraju u stanice citotrofoblasta koje su ključne u nastanku dvaju slojeva posteljice, nemigrirajućeg viloznog trofoblasta građenog od stanica sinciciotrofoblasta i invazivnog ekstraviloznog trofoblasta građenog od stanica citotrofoblasta. Ova dva sloja posteljice razlikuju se po svojim funkcijama. Ako dođe do poremećene aktivacije Hh signalnog puta i ometanja normalne signalne kaskade pa samim time i aberantne ekspresije GLI proteina, može doći do poremećaja u diferencijaciji trofoblasta što vodi razvoju raznih bolesti kao što su hidatiformna mola, invazivna mola, koriokarcinom, trofoblastični tumor ležišta posteljice i epiteloidni trofoblastični tumor. Navedene bolesti obilježene su abnormalnom proliferacijom trofoblasta te zajedno čine skup patoloških stanja posteljice zvan gestacijska trofoblastična bolest. Povezanost aberantne ekspresije GLI proteina s razvojem bolesti ukazuje na važnost pravilne regulacije ovih transkripcijskih faktora tijekom diferencijacije trofoblasta i normalnog razvoja posteljice.GLI proteins are participants of the evolutionary conserved Hedgehog (Hh) signaling pathway, which plays a key role in the proliferation and differentiation of cells and morphogenesis of particular tissues and organs. Hh signaling pathways activate by binding of Hh ligands to the PTCH transmembranous receptor. In this process SMO activates and that leads to an increased activity of the GLI transcription factors, which support the transcription of target genes. There are three isoforms of the GLI proteins in people GLI1, GLI2, GLI3, which do not have the same function because of the difference in structure. GLI proteins participate in the differentiation of trophoblasts in the development of the placenta. The stem cells of the trophoblast differentiate into cytotrophoblast cells (which play a key role in the creation of the two layers of the placenta), non-migratory villous trophoblast (built of syntitiotrophoblast cells) and an invasive extravillous trophoblast (built of cytotrophoblast cells). These two layers of the placenta differentiate in functions. If a disrupted activation of the Hh signaling pathway and disruption of a normal signaling cascade (and therefore even an aberrant expression of GLI proteins) occurs, a disruption in differentiation of the trophoblasts that leads to different diseases (such as hydatidiform mole, invasive mole, choriocarcinoma, placental site trophoblastic tumour and epitheloid trophoblastic tumour) may occur. The mentioned diseases are characterised by abnormal proliferation of trophoblasts and together make up a group of pathological conditions known as gestational trophoblastic diseases. The connection of the aberrant expression of the GLI proteins along with the development of diseases shows the importance of a standard regulation of transcription factors during the dfferentiation of trophoblasts and a normal development of the placenta

The role of GLI protein family in trophoblast cell differentiation

GLI proteini sudionici su evolucijski konzerviranog Hedgehog (Hh) signalnog puta koji tijekom embrionalnog razvoja ima ključnu ulogu u prolifereciji i diferencijaciji stanica te morfogenezi određenih tkiva i organa. Hh signalni put aktivira se vezanjem Hh liganada za PTCH transmembranski receptor pri čemu se aktivira SMO te dolazi do povećane aktivnosti GLI transkripcijskih faktora koji potiču transkripciju ciljnih gena. Kod ljudi su pronađene tri izoforme GLI proteina GLI1, GLI2 i GLI3 koji zbog razlika u građi nemaju jednaku funkciju. GLI proteini sudjeluju u diferencijaciji trofoblasta tijekom razvoja posteljice pri čemu se matične pluripotentne stanica trofoblasta diferenciraju u stanice citotrofoblasta koje su ključne u nastanku dvaju slojeva posteljice, nemigrirajućeg viloznog trofoblasta građenog od stanica sinciciotrofoblasta i invazivnog ekstraviloznog trofoblasta građenog od stanica citotrofoblasta. Ova dva sloja posteljice razlikuju se po svojim funkcijama. Ako dođe do poremećene aktivacije Hh signalnog puta i ometanja normalne signalne kaskade pa samim time i aberantne ekspresije GLI proteina, može doći do poremećaja u diferencijaciji trofoblasta što vodi razvoju raznih bolesti kao što su hidatiformna mola, invazivna mola, koriokarcinom, trofoblastični tumor ležišta posteljice i epiteloidni trofoblastični tumor. Navedene bolesti obilježene su abnormalnom proliferacijom trofoblasta te zajedno čine skup patoloških stanja posteljice zvan gestacijska trofoblastična bolest. Povezanost aberantne ekspresije GLI proteina s razvojem bolesti ukazuje na važnost pravilne regulacije ovih transkripcijskih faktora tijekom diferencijacije trofoblasta i normalnog razvoja posteljice.GLI proteins are participants of the evolutionary conserved Hedgehog (Hh) signaling pathway, which plays a key role in the proliferation and differentiation of cells and morphogenesis of particular tissues and organs. Hh signaling pathways activate by binding of Hh ligands to the PTCH transmembranous receptor. In this process SMO activates and that leads to an increased activity of the GLI transcription factors, which support the transcription of target genes. There are three isoforms of the GLI proteins in people GLI1, GLI2, GLI3, which do not have the same function because of the difference in structure. GLI proteins participate in the differentiation of trophoblasts in the development of the placenta. The stem cells of the trophoblast differentiate into cytotrophoblast cells (which play a key role in the creation of the two layers of the placenta), non-migratory villous trophoblast (built of syntitiotrophoblast cells) and an invasive extravillous trophoblast (built of cytotrophoblast cells). These two layers of the placenta differentiate in functions. If a disrupted activation of the Hh signaling pathway and disruption of a normal signaling cascade (and therefore even an aberrant expression of GLI proteins) occurs, a disruption in differentiation of the trophoblasts that leads to different diseases (such as hydatidiform mole, invasive mole, choriocarcinoma, placental site trophoblastic tumour and epitheloid trophoblastic tumour) may occur. The mentioned diseases are characterised by abnormal proliferation of trophoblasts and together make up a group of pathological conditions known as gestational trophoblastic diseases. The connection of the aberrant expression of the GLI proteins along with the development of diseases shows the importance of a standard regulation of transcription factors during the dfferentiation of trophoblasts and a normal development of the placenta

Novel Epigenetic Biomarkers in Pregnancy-Related Disorders and Cancers

As the majority of cancers and gestational diseases are prognostically stage- and grade-dependent, the ultimate goal of ongoing studies in precision medicine is to provide early and timely diagnosis of such disorders. These studies have enabled the development of various new diagnostic biomarkers, such as free circulating nucleic acids, and detection of their epigenetic changes. Recently, extracellular vesicles including exosomes, microvesicles, oncosomes, and apoptotic bodies have been recognized as powerful diagnostic tools. Extracellular vesicles carry specific proteins, lipids, DNAs, mRNAs, and miRNAs of the cells that produced them, thus reflecting the function of these cells. It is believed that exosomes, in particular, may be the optimal biomarkers of pathological pregnancies and cancers, especially those that are frequently diagnosed at an advanced stage, such as ovarian cancer. In the present review, we survey and critically appraise novel epigenetic biomarkers related to free circulating nucleic acids and extracellular vesicles, focusing especially on their status in trophoblasts (pregnancy) and neoplastic cells (cancers)