Alterations to DNA methylation and expression of CXCL14 are associated with suboptimal birth outcomes

Cheong, Clara Yujing; Chng, Keefe; Lim, Mei Kee; Amrithraj, Ajith Isaac; Joseph, Roy; Sukarieh, Rami; Tan, Yong Kiam; Chan, Louiza; Tan, Jun; Chen, Li; Pan, Hong; Holbrook, Joanna D.; Meaney, Michael J.; Chong, Yap Seng; Gluckman, Peter D.; Stünkel, Walter

doi:10.1038/jhg.2014.63

Cited by 14 publications

(8 citation statements)

References 23 publications

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“…Although CXCL14 did not affect trophoblast proliferation, trophoblast invasion and migration were suppressed by its regulation of the matrix metalloproteinases MMP-2 and MMP-9. 30 A recent study found CXCL14 expression was elevated in umbilical cords from human low birth weight infants and that this was associated with site-specific CpG methylation in the promoter of the gene, 31 leading the authors to suggest its potential utility as an early biomarker of metabolic dysfunction in the offspring. The DMRs shown in Table 2 are localized to 2 differentially methylated genes CXCL14 and RIMS1.…”

Section: Discussionmentioning

confidence: 99%

Comparison of Genome-Wide and Gene-Specific DNA Methylation Profiling in First-Trimester Chorionic Villi From Pregnancies Conceived With Infertility Treatments

Cui

Wang

et al. 2017

Reprod. Sci.

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Although global methylation patterns are similar, there are differences in methylation of specific genes in IVF compared to NIFT conceptions, leading to altered gene expression. PTCRA was differentially methylated and downregulated in IVF conceptions, warranting further investigation. It remains to be determined whether these changes affect placentation and whether it is due to the more profound underlying infertility requiring IVF, yet these data provide unique insight into the first-trimester placental epigenome.

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Section: Discussionmentioning

confidence: 99%

Comparison of Genome-Wide and Gene-Specific DNA Methylation Profiling in First-Trimester Chorionic Villi From Pregnancies Conceived With Infertility Treatments

Cui

Wang

et al. 2017

Reprod. Sci.

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“…51 Beyond cancer, regulation of CXCL14 expression by promoter methylation is also associated with immune regulation in viral and bacterial infections, 52,53 autoimmune diseases such as inflammatory bowel disease, 54 and even fetal development. 55,56 Although these studies are outside the scope of this review, it exemplifies the importance of CXCL14 expression in both normal and diseased tissues.…”

Section: Regulation Of Cxcl14 Expressionmentioning

confidence: 99%

The multifarious roles of the chemokine CXCL14 in cancer progression and immune responses

Westrich

Vermeer

Colbert

et al. 2020

Molecular Carcinogenesis

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The chemokine CXCL14 is a highly conserved, homeostatic chemokine that is constitutively expressed in skin epithelia. Responsible for immune cell recruitment and maturation, as well as impacting epithelial cell motility, CXCL14 contributes to the establishment of immune surveillance within normal epithelial layers. Furthermore, CXCL14 is critical to upregulating major histocompatibility complex class I expression on tumor cells. Given these important roles, CXCL14 is often dysregulated in several types of carcinomas including cervical, colorectal, endometrial, and head and neck cancers. Its disruption has been shown to limit critical antitumor immune regulation and is correlated to poor patient prognosis.However, other studies have found that in certain cancers, namely pancreatic and some breast cancers, overexpression of stromal CXCL14 correlates with poor patient survival due to increased invasiveness. Contributing to the ambiguity CXCL14 plays in cancer is that the native CXCL14 receptor remains uncharacterized, although several candidate receptors have been proposed.Despite the complexity of CXCL14 functions, it remains clear that this chemokine is a key regulatory factor in cancer and represents a potential target for future cancer immunotherapies. K E Y W O R D Santitumor immunity, chemokine, CXCL14, HPV, immunotherapy

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“…Firstly, MSCs may be recruited or maintained differentially near umbilical circulation, in response to intrauterine stressors such as inflammation (25) or hypoxia-ischemia (26). Secondly, deviations in stem cell differentiation and fate in response to intrauterine stress or epigenetic modifications (27, 28) might have implications for the postnatal capabilities of lung regeneration if MSC are not mobilized from Wharton's jelly at birth. Thirdly, overabundance of MSCs may contribute to ongoing lung injury (29).…”

Section: Discussionmentioning

confidence: 99%

Variations in Umbilical Cord Hematopoietic and Mesenchymal Stem Cells With Bronchopulmonary Dysplasia

et al. 2019

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Objective: To test the hypothesis that umbilical cord blood-derived CD34+ hematopoietic stem cells (HPSC), cord tissue-derived CD90+ and CD105+ mesenchymal stem cells (MSC) vary with bronchopulmonary dysplasia (BPD).Methods: We conducted a prospective longitudinal study at a large birth center (Prentice Women's Hospital in Chicago, IL). Premature infants (N = 200) were enrolled in 2:1:1 ratio based on gestational age (GA): mildly preterm (31–32 weeks), moderately preterm (29–30 weeks), and extremely preterm (23–28 weeks). Cord blood (CB) and cord tissues (CT) were collected at birth using commercial banking kits, and analyzed for collection blood volume, tissue mass, CD34+, CD90+, CD105+ counts, and concentrations. Multiplex immunoassay was used to measure 12 cytokines and growth factors in CB plasma of 74 patients. BPD severity was defined according to NIH consensus definitions. Univariate and multivariate regression models were used to identify perinatal covariates and assess associations between stem cell concentrations, cytokines, and BPD outcomes.Results: Of 200 patients enrolled (mean GA = 30 ± 2 weeks), 30 developed mild, 24 moderate, and 19 severe BPD. Concentrations of HPSC and MSC, as measured by %CD34+, %CD90+, and %CD105+ of total cells, increased with degree of prematurity. Collection parameters varied with GA, birth weight (BW), gender, prolonged rupture of membranes, mode of delivery, chorioamnionitis, and multiple gestation. Moderate-severe BPD or death was increased with lower GA, BW, Apgar scores, and documented delayed cord clamping. %CD34+ and %CD90+ were increased with BPD and directly correlated with BPD severity. Severe BPD was positively associated with %CD34+ (beta-coefficient = 0.9; 95% CI = 0.4–1.5; P < 0.01) and %CD90+ (beta-coefficient = 0.4; 95% CI = 0.2–0.6; P < 0.001) after adjustment for covariates. CB plasma granulocyte-colony stimulating factor (G-CSF) was inversely associated with %CD90+, and decreased with BPD. Below median G-CSF combined with elevated %CD90+ predicted BPD (positive predictive value = 100%).Conclusions: CB and CT collections yielded high concentrations of HPSCs and MSCs in BPD infants, accompanied by low circulating G-CSF. These variations suggest possible mechanisms by which stem cell differentiation and function predict BPD.

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Alterations to DNA methylation and expression of CXCL14 are associated with suboptimal birth outcomes

Cited by 14 publications

References 23 publications

Comparison of Genome-Wide and Gene-Specific DNA Methylation Profiling in First-Trimester Chorionic Villi From Pregnancies Conceived With Infertility Treatments

Comparison of Genome-Wide and Gene-Specific DNA Methylation Profiling in First-Trimester Chorionic Villi From Pregnancies Conceived With Infertility Treatments

The multifarious roles of the chemokine CXCL14 in cancer progression and immune responses

Variations in Umbilical Cord Hematopoietic and Mesenchymal Stem Cells With Bronchopulmonary Dysplasia

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