SNHG22 promotes migration and invasion of trophoblasts via miR-128-3p/PCDH11X axis and activates PI3K/Akt signaling pathway

Wei, Xiaoying; Yuan, Yichong; Yang, Qiong

doi:10.1016/j.clinsp.2022.100055

Cited by 4 publications

(1 citation statement)

References 32 publications

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“…We analyzed top 10 genes from heatmap by excluding pseudogenes and observed Pcdh11x was enriched in cluster 3 which is responsible for cell recognition and activation of PI3k/Akt signaling (Wei et al, 2022), Taf2 is critical in formation of RNA polymerase II initiation complex (Alpern et al, 2014), TMEM117 primarily functions in Endoplasmic reticulum (ER) stress mediated mitochondrial apoptotic pathway (Maruyama et al, 2023), Gabrg1 has a role in chloride channel activity although we could not find its relevance in leishmaniasis or macrophages, Tox is a DNA binding protein associated with control of chromatin structure majorly in activation of T-cells (Yu and Li, 2015), Fastkd3 is an unusual RNA-binding protein that critically regulates mitochondrial RNA metabolism (Boehm et al, 2016), L.major infected mice model has been reported to show significant reduction in parasite burden in lymph nodes, spleen and liver when Map2 was activiity was enhanced in vivo (Le Pape, 2008), Erap2 acts as protease to cleave antigens and form peptides which are presented by MHCI in canine leishmaniasis (Pedersen et al, 2016), Zfp606 has not been reported to have any role, Vmn2r70 is predicted to have a role in enabling G protein-coupled receptor activity. From the expression set we could infer that sleepy macrophages have a stressful environment and is highly undergoing epigenetic ad transcriptional changes to L.major infection and is preparing it to combat infection by itself and also to act as an antigen presenting cell to other immune cells.…”

Section: Discussionmentioning

confidence: 99%

Single cell ATAC sequencing identifies sleepy macrophages during reciprocity of cytokines inL.majorinfection

Khandibharad¹,

Kharat²,

Singh³

2023

Preprint

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Hallmark for macrophages is their ability to possess plasticity which enables them to respond to changing microenvironment. Leishmania takes use of the phenotypic plasticity of macrophages to create favorable position for intracellular survival and persistent infection through regulatory cytokine like IL10. However, these effector cells can eliminate infection through modulation of critical cytokines such as IL12 and key players involved in its production. Using sophisticated tool of single cell ATAC sequencing we analyzed the regulatory axis of IL10 and IL12 in time dependent manner for L.major infection in macrophages. We recognized the cellular heterogeneity post infection with the regulators of IL10 and IL12 and observed a reciprocal relationship between them. Our prominent findings also exposed sleepy macrophages and its role in IL10 and IL12 reciprocity. To summarize, role of NFAT5 was vital in identification of sleepy macrophages which is a transient state where transcription factors controlled the epigenetic remodeling and expression of genes involved in pro-inflammatory cytokine production and recruitment of immune cells.

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Section: Discussionmentioning

confidence: 99%

Single cell ATAC sequencing identifies sleepy macrophages during reciprocity of cytokines inL.majorinfection

Khandibharad¹,

Kharat²,

Singh³

2023

Preprint

View full text Add to dashboard Cite

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Single-cell ATAC sequencing identifies sleepy macrophages during reciprocity of cytokines in L. major infection

Khandibharad,

Singh

2024

Microbiol Spectr

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The hallmark characteristic of macrophages lies in their inherent plasticity, allowing them to adapt to dynamic microenvironments. Leishmania strategically modulates the phenotypic plasticity of macrophages, creating a favorable environment for intracellular survival and persistent infection through regulatory cytokine such as interleukin (IL)-10. Nevertheless, these effector cells can counteract infection by modulating crucial cytokines like IL-12 and key components involved in its production. Using sophisticated tool of single-cell assay for transposase accessible chromatin (ATAC) sequencing, we systematically examined the regulatory axis of IL-10 and IL-12 in a time-dependent manner during Leishmania major infection in macrophages Our analysis revealed the cellular heterogeneity post-infection with the regulators of IL-10 and IL-12, unveiling a reciprocal relationship between these cytokines. Notably, our significant findings highlighted the presence of sleepy macrophages and their pivotal role in mediating reciprocity between IL-10 and IL-12. To summarize, the roles of cytokine expression, transcription factors, cell cycle, and epigenetics of host cell machinery were vital in identification of sleepy macrophages, which is a transient state where transcription factors controlled the epigenetic remodeling and expression of genes involved in pro-inflammatory cytokine expression and recruitment of immune cells. IMPORTANCE Leishmaniasis is an endemic affecting 99 countries and territories globally, as outlined in the 2022 World Health Organization report. The disease’s severity is compounded by compromised host immune systems, emphasizing the pivotal role of the interplay between parasite and host immune factors in disease regulation. In instances of cutaneous leishmaniasis induced by L. major , macrophages function as sentinel cells. Our findings indicate that the plasticity and phenotype of macrophages can be modulated to express a cytokine profile involving IL-10 and IL-12, mediated by the regulation of transcription factors and their target genes post -L. major infection in macrophages. Employing sophisticated methodologies such as single-cell ATAC sequencing and computational genomics, we have identified a distinctive subset of macrophages termed “sleepy macrophages.” These macrophages exhibit downregulated housekeeping genes while expressing a unique set of variable features. This data set constitutes a valuable resource for comprehending the intricate host-parasite interplay during L. major infection.

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Role of microRNAs in trophoblast invasion and spiral artery remodeling: Implications for preeclampsia

Hayder

Shan²,

Chen³

et al. 2022

Front. Cell Dev. Biol.

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It is now well-established that microRNAs (miRNAs) are important regulators of gene expression. The role of miRNAs in placental development and trophoblast function is constantly expanding. Trophoblast invasion and their ability to remodel uterine spiral arteries are essential for proper placental development and successful pregnancy outcome. Many miRNAs are reported to be dysregulated in pregnancy complications, especially preeclampsia and they exert various regulatory effects on trophoblasts. In this review, we provide a brief overview of miRNA biogenesis and their mechanism of action, as well as of trophoblasts differentiation, invasion and spiral artery remodeling. We then discuss the role of miRNAs in trophoblasts invasion and spiral artery remodeling, focusing on miRNAs that have been thoroughly investigated, especially using multiple model systems. We also discuss the potential role of miRNAs in the pathogenesis of preeclampsia.

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SNHG22 promotes migration and invasion of trophoblasts via miR-128-3p/PCDH11X axis and activates PI3K/Akt signaling pathway

Cited by 4 publications

References 32 publications

Single cell ATAC sequencing identifies sleepy macrophages during reciprocity of cytokines inL.majorinfection

Single cell ATAC sequencing identifies sleepy macrophages during reciprocity of cytokines inL.majorinfection

Single-cell ATAC sequencing identifies sleepy macrophages during reciprocity of cytokines in L. major infection

Role of microRNAs in trophoblast invasion and spiral artery remodeling: Implications for preeclampsia

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