ORCID Profile
0000-0002-4761-9340
Current Organisation
Medical University of Graz
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Publisher: Wiley
Date: 10-2017
Publisher: Cold Spring Harbor Laboratory
Date: 11-10-2022
DOI: 10.1101/2022.10.10.511539
Abstract: Pre-ecl sia (PE) is a syndrome that affects multiple organ systems and is the most severe hypertensive disorder in pregnancy. It frequently leads to preterm delivery, maternal and fetal morbidity and mortality and life-long complications 1 . We currently lack efficient screening tools 2, 3 and early therapies 4, 5 to address PE. To investigate the early stages of early onset PE, and identify candidate markers and pathways, we performed spatio-temporal multi-omics profiling of human PE placentae and healthy controls and validated targets in early gestation in a longitudinal clinical cohort. We used a single-nuclei RNA-seq approach combined with spatial proteo- and transcriptomics and mechanistic in vitro signalling analyses to bridge the gap from late pregnancy disease to early pregnancy pathomechanisms. We discovered a key disruption in villous trophoblast differentiation, which is driven by the increase of transcriptional coactivator p300, that ultimately ends with a senescence-associated secretory phenotype (SASP) of trophoblasts. We found a significant increase in the senescence marker activin A in preecl tic maternal serum in early gestation, before the development of clinical symptoms, indicating a translation of the placental syndrome to the maternal side. Our work describes a new disease progression, starting with a disturbed transition in villous trophoblast differentiation. Our study identifies potential pathophysiology-relevant biomarkers for the early diagnosis of the disease as well as possible targets for interventions, which would be crucial steps toward protecting the mother and child from gestational mortality and morbidity and an increased risk of cardiovascular disease later in life.
Publisher: Frontiers Media SA
Date: 22-05-2019
Publisher: S. Karger AG
Date: 27-04-2016
DOI: 10.1159/000445112
Abstract: b i Objectives: /i /b A key problem in prenatal screening using extra-embryonic cells is the feasibility of extracting usable DNA from a small number of cells. Syncytial nuclear aggregates (SNAs) are multinucleated structures shed from the placenta. This study assesses the potential of SNAs as a source of fetal DNA for the detection of genetic abnormalities. b i Methods: /i /b SNAs were collected in vitro. Whole-genome lification was used to lify DNA from single SNAs, and DNA quality and quantity was assessed by spectrophotometry and PCR. Confocal microscopy was used to count nuclei within SNAs, determine metabolic activity and investigate DNA damage. Fetal sex and chromosomal/genetic abnormalities were investigated with array-comparative genomic hybridization (aCGH). b i Results: /i /b DNA was lified from 81% of the in idual SNAs. A mean of 61 ± 43 nuclei were found per SNA. DNA strand breaks were found in 76% of the SNAs. Seventy-five percent of SNAs yielded whole-genome- lified DNA of sufficient quality for aCGH after storage and shipping. In idual SNAs from the same pregnancy reliably gave the same chromosomal profile, and fetal sex and trisomies could be detected. A microdeletion was detected in one pregnancy. b i Conclusion: /i /b SNAs could provide a source of extra-embryonic DNA for the prenatal screening/diagnosis of fetal sex and chromosomal and sub-chromosomal genetic abnormalities.
Publisher: Wiley
Date: 10-2019
Abstract: These guidelines are a consensus work of a considerable number of members of the immunology and flow cytometry community. They provide the theory and key practical aspects of flow cytometry enabling immunologists to avoid the common errors that often undermine immunological data. Notably, there are comprehensive sections of all major immune cell types with helpful Tables detailing phenotypes in murine and human cells. The latest flow cytometry techniques and applications are also described, featuring ex les of the data that can be generated and, importantly, how the data can be analysed. Furthermore, there are sections detailing tips, tricks and pitfalls to avoid, all written and peer‐reviewed by leading experts in the field, making this an essential research companion.
Publisher: Elsevier BV
Date: 12-2017
DOI: 10.1016/J.JMB.2017.10.011
Abstract: The highly fine-tuned dynamics of cell cycle gene expression have been intensely studied for several decades. However, some previous observations may be difficult to fully decouple from artifacts induced by traditional cell synchronization procedures. In addition, bulk cell measurements may have disguised intricate details. Here, we address this by sorting and transcriptomic sequencing of single cells progressing through the cell cycle without prior synchronization. Genes and pathways with known cell cycle roles are confirmed, associated regulatory sequence motifs are determined, and we also establish ties between other biological processes and the unsynchronized cell cycle. Importantly, we find the G1 phase to be surprisingly heterogeneous, with transcriptionally distinct early and late time points. We additionally note that mRNAs accumulate to reach maximum total levels at mitosis and find that stable transcripts show reduced cell-to-cell variability, consistent with the transcriptional burst model of gene expression. Our study provides the first detailed transcriptional profiling of an unsynchronized human cell cycle.
No related grants have been discovered for Thomas Kroneis.