Publications

@article{nokey_80,

title = {Exploring the genomic landscape of Chlamydiifrater species: novel features include multiple truncated major outer membrane proteins, unique genes and chlamydial plasticity zone orthologs},

author = {Martin Hölzer and Charlotte Reuschel and Fabien Vorimore and Karine Laroucau and Konrad Sachse},

doi = {10.1099/acmi.0.000936.v3},

year  = {2025},

date = {2025-02-03},

urldate = {2025-02-03},

journal = {Access Microbiology},

volume = {7},

abstract = {Recently discovered obligate intracellular bacteria belonging to the genus Chlamydiifrater with the species of Chlamydiifrater phoenicopteri and Chlamydiifrater volucris were studied to explore the composition of their genomes and their relatedness to Chlamydia, the other genus of the family Chlamydiaceae. We investigated 4 isolates of Cf. volucris, 2 of them newly sequenced, and one of Cf. phoenicopteri alongside 12 representatives of the Chlamydia species. Our study uncovers previously unrecognized genomic structures within Chlamydiifrater using a hybrid sequencing approach and advanced annotation pipelines, providing insights into species-specific adaptations and evolutionary dynamics. The integration of long-read sequencing data, comprehensive re-annotation strategies and pan-genomics enabled the localization of the unique plasticity zone and the identification of novel gene clusters in Chlamydiifrater strains, which improves our understanding of chlamydial genome architecture and plasticity in the family Chlamydiaceae. Our analysis revealed that 761 CDS (~80%) are shared among members of both genera. We further identified 158 unique genes of Chlamydiifrater species, but their annotation remains challenging because of the absence of functionally annotated orthologs in public databases. A full-length ompA gene encoding the major outer membrane porin was seen in all Chlamydiifrater strains. We also describe the localization and structure of multiple truncated CDS of ompA family members, representing one of this study’s most interesting findings. While genome analysis of Chlamydiifrater spp. confirmed numerous common features shared with representatives of the genus Chlamydia, many unique genomic elements were identified that underpin the distinct phenotype and separate genetic position of these new microorganisms.},

keywords = {annotation, bacteria, DNA / genomics, evolution, pregnancy},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {Identification of altered miRNAs and their targets in placenta accreta},

author = {José M Murrieta-Coxca and Emanuel Barth and Paulina Fuentes-Zacarias and Ruby N Gutiérrez-Samudio and Tanja Groten and Alexandra Gellhaus and Angela Köninger and Manja Marz and Udo R Markert and Diana M Morales-Prieto

},

doi = {10.3389/fendo.2023.1021640},

year  = {2023},

date = {2023-03-03},

journal = {Front Endocrinol},

volume = {14},

pages = {1021640},

abstract = {Placenta accreta spectrum (PAS) is one of the major causes of maternal morbidity and mortality worldwide with increasing incidence. PAS refers to a group of pathological conditions ranging from the abnormal attachment of the placenta to the uterus wall to its perforation and, in extreme cases, invasion into surrounding organs. Among them, placenta accreta is characterized by a direct adhesion of the villi to the myometrium without invasion and remains the most common diagnosis of PAS. Here, we identify the potential regulatory miRNA and target networks contributing to placenta accreta development. Using small RNA-Seq followed by RT-PCR confirmation, altered miRNA expression, including that of members of placenta-specific miRNA clusters (e.g., C19MC and C14MC), was identified in placenta accreta samples compared to normal placental tissues. In situ hybridization (ISH) revealed expression of altered miRNAs mostly in trophoblast but also in endothelial cells and this profile was similar among all evaluated degrees of PAS. Kyoto encyclopedia of genes and genomes (KEGG) analyses showed enriched pathways dysregulated in PAS associated with cell cycle regulation, inflammation, and invasion. mRNAs of genes associated with cell cycle and inflammation were downregulated in PAS. At the protein level, NF-κB was upregulated while PTEN was downregulated in placenta accreta tissue. The identified miRNAs and their targets are associated with signaling pathways relevant to controlling trophoblast function. Therefore, this study provides miRNA:mRNA associations that could be useful for understanding PAS onset and progression.},

keywords = {ncRNAs, pregnancy, RNA / transcriptomics},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {The Role of Non-Coding RNAs in the Human Placenta},

author = {Milena Žarković and Franziska Hufsky and Udo R Markert and Manja Marz},

doi = {10.3390/cells11091588},

year  = {2022},

date = {2022-05-09},

journal = {Cells},

volume = {11},

issue = {9},

pages = {1588},

abstract = {Non-coding RNAs (ncRNAs) play a central and regulatory role in almost all cells, organs, and species, which has been broadly recognized since the human ENCODE project and several other genome projects. Nevertheless, a small fraction of ncRNAs have been identified, and in the placenta they have been investigated very marginally. To date, most examples of ncRNAs which have been identified to be specific for fetal tissues, including placenta, are members of the group of microRNAs (miRNAs). Due to their quantity, it can be expected that the fairly larger group of other ncRNAs exerts far stronger effects than miRNAs. The syncytiotrophoblast of fetal origin forms the interface between fetus and mother, and releases permanently extracellular vesicles (EVs) into the maternal circulation which contain fetal proteins and RNA, including ncRNA, for communication with neighboring and distant maternal cells. Disorders of ncRNA in placental tissue, especially in trophoblast cells, and in EVs seem to be involved in pregnancy disorders, potentially as a cause or consequence. This review summarizes the current knowledge on placental ncRNA, their transport in EVs, and their involvement and pregnancy pathologies, as well as their potential for novel diagnostic tools.},

keywords = {extracellular vesicles, ncRNAs, pregnancy, RNA / transcriptomics},

pubstate = {published},

tppubtype = {article}

}

@article{Morales-Prieto:19,

title = {Identification of miRNAs and associated pathways regulated by Leukemia Inhibitory Factor in trophoblastic cell lines.},

author = {Diana M. Morales-Prieto and Emanuel Barth and Jose Martín Murrieta-Coxca and Rodolfo R. Favaro and Ruby N. Gutiérrez-Samudio and Wittaya Chaiwangyen and Stephanie Ospina-Prieto and Bernd Gruhn and Ekkehard Schleußner and Manja Marz and Udo R. Markert},

doi = {10.1016/j.placenta.2019.09.005},

year  = {2019},

date = {2019-09-12},

urldate = {2019-09-12},

journal = {Placenta},

volume = {88},

pages = {20--27},

abstract = {Leukemia Inhibitory Factor (LIF) regulates behavior of trophoblast cells and their interaction with immune and endothelial cells. In vitro, trophoblast cell response to LIF may vary depending on the cell model. Reported differences in the miRNA profile of trophoblastic cells may be responsible for these observations. Therefore, miRNA expression was investigated in four trophoblastic cell lines under LIF stimulation followed by in silico analysis of altered miRNAs and their associated pathways. Low density TaqMan miRNA assays were used to quantify levels of 762 mature miRNAs under LIF stimulation in three choriocarcinoma-derived (JEG-3, ACH-3P and AC1-M59) and a trophoblast immortalized (HTR-8/SVneo) cell lines. Expression of selected miRNAs was confirmed in primary trophoblast cells and cell lines by qPCR. Targets and associated pathways of the differentially expressed miRNAs were inferred from the miRTarBase followed by a KEGG Pathway Enrichment Analysis. HTR-8/SVneo and JEG-3 cells were transfected with miR-21-mimics and expression of miR-21 targets was assessed by qPCR. A similar number of miRNAs changed in each tested cell line upon LIF stimulation, however, low coincidence of individual miRNA species was observed and occurred more often among choriocarcinoma-derived cells (complete data set at http://www.ncbi.nlm.nih.gov/geo/ under GEO accession number GSE130489). Altered miRNAs were categorized into pathways involved in human diseases, cellular processes and signal transduction. Six cascades were identified as significantly enriched, including JAK/STAT and TGFB-SMAD. Upregulation of miR-21-3p was validated in all cell lines and primary cells and STAT3 was confirmed as its target. Dissimilar miRNA responses may be involved in differences of LIF effects on trophoblastic cell lines.},

keywords = {differential expression analysis, ncRNAs, pregnancy},

pubstate = {published},

tppubtype = {article}

}

@article{Dukhovny:19,

title = {A CRISPR activation screen identifies genes protecting from Zika virus infection},

author = {Anna Dukhovny and Kevin Lamkiewicz and Qian Chen and Markus Fricke and Nabila Jabrane-Ferrat and Manja Marz and Jae U. Jung and Ella H. Sklan},

doi = {10.1128/JVI.00211-19},

year  = {2019},

date = {2019-07-30},

urldate = {2019-07-30},

journal = {J Virol},

volume = {93},

number = {16},

publisher = {American Society for Microbiology Journals},

abstract = {Zika virus (ZIKV) is an arthropod borne emerging pathogen causing febrile illness. ZIKV is associated Guillain-Barré syndrome and other neurological complications. Infection during pregnancy is associated with pregnancy complications and developmental and neurological abnormalities collectively defined as congenital Zika syndrome. There is still no vaccine or specific treatment for ZIKV infection. To identify host factors that can rescue cells from ZIKV infection we used a genome scale CRISPR activation screen. Our highly ranking hits included a short list of interferon stimulated genes (ISGs) previously reported to have antiviral activity. Validation of the screen results highlighted IFNL2 and IFI6 as genes providing high levels of protection from ZIKV. Activation of these genes had an effect on an early stage in viral infection. In addition, infected cells expressing sgRNAs for both of these genes displayed lower levels of cell death compared to controls. Furthermore, the identified genes were significantly induced in ZIKV infected placenta explants. Thus, these results highlight a set of ISGs directly relevant for rescuing cells from ZIKV infection or its associated cell death and substantiates CRISPR activation screens as a tool to identify host factors impeding pathogen infection.IMPORTANCE Zika virus (ZIKV) is an emerging vector-borne pathogen causing a febrile disease. ZIKV infection might also trigger Guillain-Barré syndrome, neuropathy and myelitis. Vertical transmission of ZIKV can cause fetus demise, still birth or severe congenital abnormalities and neurological complications. There is no vaccine or specific antiviral treatment against ZIKV. We used a genome wide CRISPR activation screen, where genes are activated from their native promoters to identify host cell factors that protect cells from ZIKV infection or associated cell death. The results provide better understanding of key host factors that protect cells from ZIKV infection and might assist in identifying novel antiviral targets.},

keywords = {pregnancy, RNA / transcriptomics, virus host interaction, viruses},

pubstate = {published},

tppubtype = {article}

}

@article{Chaiwangyen:17,

title = {KL 5 Trophoblast-immune cell communication via microRNA transported in extracellular vesicles},

author = {Wittaya Chaiwangyen and Ruby N. Gutiérrez-Samudio and Udo R. Markert and Manja Marz and Diana M. Morales-Prieto and Stephanie Ospina-Prieto},

year  = {2017},

date = {2017-01-01},

urldate = {2017-01-01},

journal = {Pregnancy Hypertens},

volume = {9},

pages = {5},

publisher = {Elsevier},

keywords = {ncRNAs, pregnancy},

pubstate = {published},

tppubtype = {article}

}