Редактирование: CDX2 (раздел)

==Publications==

{{medline-entry
|title=Maternal ageing impairs mitochondrial DNA kinetics during early embryogenesis in mice.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/31174209
|abstract=Does ageing affect the kinetics of the mitochondrial pool during oogenesis and early embryogenesis? While we found no age-related change during oogenesis, the kinetics of mitochondrial DNA content and the expression of the factors involved in mitochondrial biogenesis appeared to be significantly altered during embryogenesis. Oocyte mitochondria are necessary for embryonic development. The morphological and functional alterations of mitochondria, as well as the qualitative and quantitative mtDNA anomalies, observed during ovarian ageing may be responsible for the alteration of oocyte competence and embryonic development. The study, conducted from November 2016 to November 2017, used 40 mice aged 5-8 weeks and 45 mice aged 9-11 months (C57Bl6/CBA F(1)). A total of 488 immature oocytes, with a diameter ranging from 20 μm to more than 80 μm, were collected from ovaries, and 1088 mature oocytes or embryos at different developmental stages (two PN, one-cell, i.e. syngamy, two-cell, four-cell, eight-cell, morula and blastocyst) were obtained after ovarian stimulation and, for embryos, mating. Mitochondrial DNA was quantified by quantitative PCR. We used quantitative reverse transcriptase PCR (RT-PCR) (microfluidic method) to study the relative expression of three genes involved in the key steps of embryogenesis, i.e. embryonic genome activation (HSPA1) and differentiation ([[CDX2]] and [[NANOG]]), two mtDNA genes (CYB and ND2) and five genes essential for mitochondrial biogenesis ([[PPARGC1A]], [[NRF1]], [[POLG]], [[TFAM]] and PRKAA). The statistical analysis was based on mixed linear regression models applying a logistic link function (STATA v13.1 software), with values of P < 0.05 being considered significant. During oogenesis, there was a significant increase in oocyte mtDNA content (P < 0.0001) without any difference between the two groups of mice (P = 0.73). During the first phase of embryogenesis, i.e. up to the two-cell stage, embryonic mtDNA decreased significantly in the aged mice (P < 0.0001), whereas it was stable for young mice (young/old difference P = 0.015). The second phase of embryogenesis, i.e. between the two-cell and eight-cell stages, was characterized by a decrease in embryonic mtDNA for young mice (P = 0.013) only (young/old difference P = 0.038). During the third phase, i.e. between the eight-cell and blastocyst stage, there was a significant increase in embryonic mtDNA content in young mice (P < 0.0001) but not found in aged mice (young/old difference P = 0.002). We also noted a faster expression of [[CDX2]] and [[NANOG]] in the aged mice than in the young mice during the second (P = 0.007 and P = 0.02, respectively) and the third phase (P = 0.01 and P = 0.008, respectively) of embryogenesis. The expression of mitochondrial genes CYB and ND2 followed similar kinetics and was equivalent for both groups of mice, with a significant increase during the third phase (P < 0.01). Of the five genes involved in mitochondrial biogenesis, i.e. [[PPARGC1A]], [[NRF1]], [[POLG]], [[TFAM]] and PRKAA, the expression of three genes decreased significantly during the first phase only in young mice ([[NRF1]], P = 0.018; [[POLG]]A, P = 0.002; PRKAA, P = 0.010), with no subsequent difference compared to old mice. In conclusion, during early embryogenesis in the old mice, we suspect that the lack of a replicatory burst before the two-cell stage, associated with the early arrival at the minimum threshold value of mtDNA, together with the absence of an increase of mtDNA during the last phase, might potentially deregulate the key stages of early embryogenesis. N/A. Because of the ethical impossibility of working on a human, this study was conducted only on a murine model. As superovulation was used, we cannot totally exclude that the differences observed were, at least partially, influenced by differences in ovarian response between young and old mice. Our findings suggest a pathophysiological explanation for the link observed between mitochondria and the deterioration of oocyte quality and early embryonic development with age. This work was supported by the University of Angers, France, by the French national research centres INSERM and the CNRS and, in part, by PHASE Division, INRA. There are no competing interests.
|mesh-terms=* Aging
* Animals
* Anti-Mullerian Hormone
* DNA, Mitochondrial
* Embryo, Mammalian
* Embryonic Development
* Female
* Male
* Maternal Age
* Mice, Inbred C57BL
* Mice, Inbred CBA
* Mitochondria
* Oocytes
* Oogenesis
* Organelle Biogenesis
* Ovary
* Pregnancy
|keywords=* ageing
* embryogenesis
* mitochondria
* mitochondrial DNA
* oogenesis
|full-text-url=https://sci-hub.do/10.1093/humrep/dez054
}}
{{medline-entry
|title=Autophagic homeostasis is required for the pluripotency of cancer stem cells.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/27929731
|abstract=Pluripotency is an important feature of cancer stem cells (CSCs) that contributes to self-renewal and chemoresistance. The maintenance of pluripotency of CSCs under various pathophysiological conditions requires a complex interaction between various cellular pathways including those involved in homeostasis and energy metabolism. However, the exact mechanisms that maintain the CSC pluripotency remain poorly understood. In this report, using both human and murine models of CSCs, we demonstrate that basal levels of autophagy are required to maintain the pluripotency of CSCs, and that this process is differentially regulated by the rate-limiting enzyme in the NAD  synthesis pathway [[NAMPT]] (nicotinamide phosphoribosyltransferase) and the transcription factor [[POU5F1]]/OCT4 (POU class 5 homeobox 1). First, our data show that the pharmacological inhibition and knockdown (K ) of [[NAMPT]] or the K  of [[POU5F1]] in human CSCs significantly decreased the expression of pluripotency markers [[POU5F1]], [[NANOG]] (Nanog homeobox) and [[SOX2]] (SRY-box 2), and upregulated the differentiation markers [[TUBB3]] (tubulin β 3 class III), [[CSN2]] (casein β), [[SPP1]] (secreted phosphoprotein 1), [[GATA6]] (GATA binding protein 6), T (T brachyury transcription factor) and [[CDX2]] (caudal type homeobox 2). Interestingly, these pluripotency-regulating effects of [[NAMPT]] and [[POU5F1]] were accompanied by contrasting levels of autophagy, wherein [[NAMPT]] K  promoted while [[POU5F1]] K  inhibited the autophagy machinery. Most importantly, any deviation from the basal level of autophagy, either increase (via rapamycin, serum starvation or Tat-beclin 1 [Tat-BECN1] peptide) or decrease (via [[ATG7]] or [[ATG12]] K ), strongly decreased the pluripotency and promoted the differentiation and/or senescence of CSCs. Collectively, these results uncover the link between the NAD  biosynthesis pathway, CSC transcription factor [[POU5F1]] and pluripotency, and further identify autophagy as a novel regulator of pluripotency of CSCs.
|mesh-terms=* Animals
* Autophagy
* Beclin-1
* Cell Differentiation
* Cell Proliferation
* Cell Survival
* Cellular Senescence
* Cytokines
* Doxorubicin
* Homeostasis
* Mice
* Models, Biological
* Neoplastic Stem Cells
* Nicotinamide Phosphoribosyltransferase
* Octamer Transcription Factor-3
* PTEN Phosphohydrolase
* Phosphorylation
* Pluripotent Stem Cells
* Proto-Oncogene Proteins c-akt
* Signal Transduction
* Sirolimus
* TOR Serine-Threonine Kinases
|keywords=* POU5F1/Oct4
* autophagy
* cancer stem cells
* differentiation
* pluripotency
* senescence
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5324853
}}
{{medline-entry
|title=Interaction of Toll-like receptors with bacterial components induces expression of [[CDX2]] and [[MUC2]] in rat biliary epithelium in vivo and in culture.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/17417665
|abstract=The mechanism of transformation of biliary epithelium leading to intestinal metaplasia, which is significantly involved in biliary diseases, remains unclear. [[CDX2]], an intestine-specific transcription factor, is thought to regulate intestinal mucin [[MUC2]] (mucus core protein) expression. We took advantage of polycystic kidney (PCK) rats as a model of chronic suppurative cholangitis with intestinal metaplasia and of cultured biliary epithelial cells (BECs) from PCK rats to clarify the causal relation between bacterial components such as pathogen-associated molecular patterns (PAMPs) and the development of intestinal metaplasia of bile ducts. Histological, immunohistochemical, and in situ hybridization studies were conducted in PCK rat livers. In cultured BECs, [[CDX2]] and [[MUC2]] were expressed following treatment with PAMPs and inhibitors (anti-Toll-like receptor (TLR)2/[[TLR4]] antibody, nuclear factor-kappaB (NF-kappaB) inhibitor MG132). Chronic suppurative cholangitis with intestinal metaplasia developed as the PCK rats aged, and intestinal metaplasia and aberrant [[CDX2]] and [[MUC2]] expression developed in parallel. Intraluminal bacteria and the expression of [[TLR2]] and [[TLR4]] in BECs were demonstrated in the bile ducts, showing chronic suppurative cholangitis. In cultured BECs, treatment with PAMPs induced upregulation of [[CDX2]] and [[MUC2]] expression, and this effect was abolished by pretreatment with anti-[[TLR2]] and anti-[[TLR4]] antibody and MG132. A knockdown of [[CDX2]] by [[CDX2]] small interfering RNA inhibited [[MUC2]] expression in cultured BECs induced by PAMPs, and transfection of [[CDX2]] expression vector induced [[MUC2]] expression. In conclusion, bacterial components may induce upregulation of the [[CDX2]] expression followed by [[MUC2]] expression via TLR and the NF-kappaB system in cultured BECs, and could be related to the development of intestinal metaplasia of the bile ducts.
|mesh-terms=* Aging
* Animals
* Bacterial Proteins
* Bile Ducts, Intrahepatic
* CDX2 Transcription Factor
* Caroli Disease
* Cells, Cultured
* Cysteine Proteinase Inhibitors
* Disease Models, Animal
* Epithelial Cells
* Fluorescent Antibody Technique, Indirect
* Homeodomain Proteins
* Immunohistochemistry
* In Situ Hybridization
* In Vitro Techniques
* Leupeptins
* Male
* Metaplasia
* Mucin-2
* Mucins
* RNA, Messenger
* Rats
* Rats, Inbred Strains
* Toll-Like Receptor 2
* Toll-Like Receptor 4
* Trans-Activators

|full-text-url=https://sci-hub.do/10.1038/labinvest.3700556
}}