Sirvi Autor "Koel, Mariann" järgi

Tulemuste filtreerimiseks trükkige paar esimest tähte
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    A molecular tool for menstrual cycle phase dating of endometrial samples in endometriosis transcriptome studies
    (2019) Saare, Merli; Merli, Triin; Teder, Hindrek; Paluoja, Priit; Palta, Priit; Koel, Mariann; Kirss, Fred; Karro, Helle; Sõritsa, Deniss; Salumets, Andres; Krjutškov, Kaarel; Peters, Maire
    Transcriptome profiling of 57 endometrial receptivity genes specifies the menstrual cycle phase of endometrial samples.
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    Endometrial receptivity revisited: endometrial transcriptome adjusted for tissue cellular heterogeneity
    (2018) Suhorutshenko, Marina; Kukushkina, Viktorija; Velthut-Meikas, Agne; Altmäe, Signe; Peters, Maire; Mägi, Reedik; Krjutškov, Kaarel; Koel, Mariann; Codoñer, Francisco M; Martinez-Blanch, Juan Fco; Vilella, Felipe; Simón, Carlos; Salumets, Andres; Laisk, Triin
    STUDY QUESTION Does cellular composition of the endometrial biopsy affect the gene expression profile of endometrial whole-tissue samples? SUMMARY ANSWER The differences in epithelial and stromal cell proportions in endometrial biopsies modify the whole-tissue gene expression profiles and affect the results of differential expression analyses. WHAT IS ALREADY KNOWN Each cell type has its unique gene expression profile. The proportions of epithelial and stromal cells vary in endometrial tissue during the menstrual cycle, along with individual and technical variation due to the method and tools used to obtain the tissue biopsy. STUDY DESIGN, SIZE, DURATION Using cell-population specific transcriptome data and computational deconvolution approach, we estimated the epithelial and stromal cell proportions in whole-tissue biopsies taken during early secretory and mid-secretory phases. The estimated cellular proportions were used as covariates in whole-tissue differential gene expression analysis. Endometrial transcriptomes before and after deconvolution were compared and analysed in biological context. PARTICIPANTS/MATERIAL, SETTING, METHODS Paired early- and mid-secretory endometrial biopsies were obtained from 35 healthy, regularly cycling, fertile volunteers, aged 23–36 years, and analysed by RNA sequencing. Differential gene expression analysis was performed using two approaches. In one of them, computational deconvolution was applied as an intermediate step to adjust for the proportions of epithelial and stromal cells in the endometrial biopsy. The results were then compared to conventional differential expression analysis. Ten paired endometrial samples were analysed with qPCR to validate the results. MAIN RESULTS AND THE ROLE OF CHANCE The estimated average proportions of stromal and epithelial cells in early secretory phase were 65% and 35%, and during mid-secretory phase, 46% and 54%, respectively, correlating well with the results of histological evaluation (r = 0.88, P = 1.1 × 10−6). Endometrial tissue transcriptomic analysis showed that approximately 26% of transcripts (n = 946) differentially expressed in receptive endometrium in cell-type unadjusted analysis also remain differentially expressed after adjustment for biopsy cellular composition. However, the other 74% (n = 2645) become statistically non-significant after adjustment for biopsy cellular composition, underlining the impact of tissue heterogeneity on differential expression analysis. The results suggest new mechanisms involved in endometrial maturation, involving genes like LINC01320, SLC8A1 and GGTA1P, described for the first time in context of endometrial receptivity. LARGE-SCALE DATA The RNA-seq data presented in this study is deposited in the Gene Expression Omnibus database with accession number GSE98386. LIMITATIONS REASONS FOR CAUTION Only dominant endometrial cell types were considered in gene expression profile deconvolution; however, other less frequent endometrial cell types also contribute to the whole-tissue gene expression profile. WIDER IMPLICATIONS OF THE FINDINGS The better understanding of molecular processes during transition from pre-receptive to receptive endometrium serves to improve the effectiveness and personalization of assisted reproduction protocols. Biopsy cellular composition should be taken into account in future endometrial ‘omics’ studies, where tissue heterogeneity could potentially influence the results. STUDY FUNDING/COMPETING INTEREST(S) This study was funded by: Estonian Ministry of Education and Research (grant IUT34-16); Enterprise Estonia (EU48695); the EU-FP7 Eurostars program (NOTED, EU41564); the EU-FP7 Marie Curie Industry-Academia Partnerships and Pathways (SARM, EU324509); Horizon 2020 innovation program (WIDENLIFE, EU692065); MSCA-RISE-2015 project MOMENDO (No 691058) and the Miguel Servet Program Type I of Instituto de Salud Carlos III (CP13/00038); Spanish Ministry of Economy, Industry and Competitiveness (MINECO) and European Regional Development Fund (FEDER): grants RYC-2016-21199 and ENDORE SAF2017-87526. Authors confirm no competing interests.
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    Globin mRNA reduction for whole-blood transcriptome sequencing
    (Scientific Reports, 2016) Krjutškov, Kaarel; Koel, Mariann; Roost, Anne Mari; Katayama, Shintaro; Einarsdottir, Elisabet; Jouhilahti, Eeva-Mari; Söderhäll, Cilla; Jaakma, Ülle; Plaas, Mario; Vesterlund, Liselotte; Lohi, Hannes; Salumets, Andres; Kere, Juha
    The transcriptome analysis of whole-blood RNA by sequencing holds promise for the identification and tracking of biomarkers; however, the high globin mRNA (gmRNA) content of erythrocytes hampers whole-blood and buffy coat analyses. We introduce a novel gmRNA locking assay (GlobinLock, GL) as a robust and simple gmRNA reduction tool to preserve RNA quality, save time and cost. GL consists of a pair of gmRNA-specific oligonucleotides in RNA initial denaturation buffer that is effective immediately after RNA denaturation and adds only ten minutes of incubation to the whole cDNA synthesis procedure when compared to non-blood RNA analysis. We show that GL is fully effective not only for human samples but also for mouse and rat, and so far incompletely studied cow, dog and zebrafish.
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    In vitro fertilization does not increase the incidence of de novo copy number alterations in fetal and placental lineages
    (Nature Medicine, 2019-11-04) Esteki, Masoud Zamani; Viltrop, Triin; Tšuiko, Olga; Tiirats, Airi; Koel, Mariann; Nõukas, Margit; Žilina, Olga; Teearu, Katre; Marjonen, Heidi; Kahila, Hanna; Meekels, Jeroen; Söderström-Anttila, Viveca; Suikkari, Anne-Maria; Tiitinen, Aila; Mägi, Reedik; Kõks, Sulev; Kaminen-Ahola, Nina; Kurg, Ants; Voet, Thierry; Vermeesch, Joris Robert; Salumets, Andres
    Although chromosomal instability (CIN) is a common phenomenon in cleavage-stage embryogenesis following in vitro fertilization (IVF)1,2,3, its rate in naturally conceived human embryos is unknown. CIN leads to mosaic embryos that contain a combination of genetically normal and abnormal cells, and is significantly higher in in vitro-produced preimplantation embryos as compared to in vivo-conceived preimplantation embryos4. Even though embryos with CIN-derived complex aneuploidies may arrest between the cleavage and blastocyst stages of embryogenesis5,6, a high number of embryos containing abnormal cells can pass this strong selection barrier7,8. However, neither the prevalence nor extent of CIN during prenatal development and at birth, following IVF treatment, is well understood. Here we profiled the genomic landscape of fetal and placental tissues postpartum from both IVF and naturally conceived children, to investigate the prevalence and persistence of large genetic aberrations that probably arose from IVF-related CIN. We demonstrate that CIN is not preserved at later stages of prenatal development, and that de novo numerical aberrations or large structural DNA imbalances occur at similar rates in IVF and naturally conceived live-born neonates. Our findings affirm that human IVF treatment has no detrimental effect on the chromosomal constitution of fetal and placental lineages.
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    TAC-seq: targeted DNA and RNA sequencing for precise biomarker molecule counting
    (2018) Teder, Hindrek; Koel, Mariann; Paluoja, Priit; Jatsenko, Tatjana; Rekker, Kadri; Laisk-Podar, Triin; Kukuškina, Viktorija; Velthut-Meikas, Agne; Fjodorova, Olga; Peters, Maire; Kere, Juha; Salumets, Andres; Palta, Priit; Krjutškov, Kaarel
    Targeted next-generation sequencing (NGS) methods have become essential in medical research and diagnostics. In addition to NGS sensitivity and high-throughput capacity, precise biomolecule counting based on unique molecular identifier (UMI) has potential to increase biomolecule detection accuracy. Although UMIs are widely used in basic research its introduction to clinical assays is still in progress. Here, we present a robust and cost-effective TAC-seq (Targeted Allele Counting by sequencing) method that uses UMIs to estimate the original molecule counts of mRNAs, microRNAs, and cell-free DNA. We applied TAC-seq in three different clinical applications and compared the results with standard NGS. RNA samples extracted from human endometrial biopsies were analyzed using previously described 57 mRNA-based receptivity biomarkers and 49 selected microRNAs at different expression levels. Cell-free DNA aneuploidy testing was based on cell line (47,XX, +21) genomic DNA. TAC-seq mRNA profiling showed identical clustering results to transcriptome RNA sequencing, and microRNA detection demonstrated significant reduction in amplification bias, allowing to determine minor expression changes between different samples that remained undetermined by standard NGS. The mimicking experiment for cell-free DNA fetal aneuploidy analysis showed that TAC-seq can be applied to count highly fragmented DNA, detecting significant (p = 7.6 × 10−4) excess of chromosome 21 molecules at 10% fetal fraction level. Based on three proof-of-principle applications we demonstrate that TAC-seq is an accurate and highly potential biomarker profiling method for advanced medical research and diagnostics.
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    The molecular interactions between trophoblast and endometrial cells in embryo implantation
    (2023-10-02) Koel, Mariann; Salumets, Andres, juhendaja; Jaks, Viljar, juhendaja; Krjutškov, Kaarel, juhendaja; Tartu Ülikool. Loodus- ja täppisteaduste valdkond
    Uue elu algus ja rasedus võivad esmapilgul tunduda üks loomulikumaid etappe naise elus, samas on see osutunud paljude paaride jaoks tõsiseks proovikiviks. Kuigi kehavälise viljastamise abiga sünnib igal aastal üha enam lapsi, siis endiselt ei õnnestu paljudel naistel seeläbi rasestuda. Mõistetavatel eetilistel põhjustel ei ole inimese embrüo pesastumist võimalik uurida naise organismis, seega on alternatiivsed uuringud vajalikud, mõistmaks mehhanisme, mis reguleerivad embrüo kinnitumist. Käesolev doktoritöö keskendub molekulaarsele suhtlusele endomeetriumi ja embrüo trofoblasti rakkude vahel. Kirjeldab naise endomeetriumi koe küpsemist ning selle protsessi seost geeniekspressiooni mustri muutustega kahes põhilises endomeetriumi rakutüübis - strooma ja epiteeli rakkudes. Selle uuringu põhjal töötati välja uus geenide aktiivsuse analüüsi meetod, mille abil määratakse endomeetriumi retseptiivsuseks oluliste RNA molekulide taset, eesmärgiga leida viljatusravi saava naise jaoks embrüo siirdamiseks parim aeg. Põhinedes rakutüübi-põhistele geenide avaldumise andmetele kirjeldati ligikaudu 550 valk-valk seost, mis moodustavad molekulaarse võrgustiku embrüo ja endomeetriumi rakkude vahel ning on vajalikud uue elu alguseks. Lisaks embrüo kinnitumisele on raseduse edukaks lõpuni kandmiseks vajalik õigesti arenev platsenta, mis võimaldab lootel normaalselt kasvada ja areneda. Selleks on määrava tähtsusega trofoblasti rakkude diferentseerumine. Doktoritöös uuriti inimese embrüonaalsete tüvirakkude diferentseerimise meetodeid trofoblasti-sarnasteks rakkudeks läbi BMP4 signaaliraja aktiveerimise ja TGBβ ja FGF2 signaaliradade inhibeerimise. Siin esitatud teadmised on oluliseks panuseks tulevastesse reproduktiivuuringutesse. Luues uusi võimalusi embrüo edukaks siirdamiseks ning uute prognostiliste ja diagnostiliste biomarkerite arendamiseks, mida kasutada viljatuse diagnostikas ning ravi optimeerimises.
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    Trofoblasti rakuliini HTR-8/SVneo mikrovesiikulite ja eksosoomide sisenemine endomeetriumi rakuliinide RL95-2 ja HEC-1A rakkudesse
    (Tartu Ülikool, 2016) Lavrits, Arina; Ingerpuu, Sulev; Koel, Mariann; Tartu Ülikool. Loodus- ja tehnoloogiateaduskond; Tartu Ülikool. Molekulaar- ja rakubioloogia instituut
    Nii retseptoorse kui ka mitteretseptoorse endomeetriumi kartsinoomi rakuliinide rakud võtavad sisse trofoblasti rakuliini HTR8/SVneo rakkudest pärit mikrovesiikuleid ja eksosoome, kusjuures HEC-1A rakkudesse mikrovesiikulid sisenevad põhimõtteliselt makropinotsütoosi ja klatriin-vahendatud endotsütoosi teel. RL95-2 rakkude kohta ei saa praegu öelda, mis mehhanismi mikrovesiikulid kasutavad rakkudesse sisenemiseks. Kuid kuivõrd tegemist on kasvajaliste rakkudega, siis ei ole saadud tulemuste põhjal võimalik öelda, kas see kehtib ka normaalsete rakkude puhul. Edasises töös tuleb siiski arvestada, et normaalsete trofoblastide ja endomeetriumirakkude kasvatamine on väga keeruline ning siiani puuduvad andmed kuivõrd efektiivselt toimub nendest rakkudest vesiikulite sekreteerimine.
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    Trofoblasti rakuliinide JAR ja JEG-3 mikrovesiikulite proteoomiline analüüs ja nende sissevõtmine endomeetriumi rakuliini RL95-2
    (Tartu Ülikool, 2013) Koel, Mariann; Ingerpuu, Sulev, juhendaja; Salumets, Andres, juhendaja; Tartu Ülikool. Loodus- ja tehnoloogaiteaduskond; Tartu Ülikool. Molekulaar- ja rakubioloogia instituut