Article
Cell Biology
Teka Khan, Arun S. Seetharam, Jie Zhou, Nathan J. Bivens, Danny J. Schust, Toshihiko Ezashi, Geetu Tuteja, R. Michael Roberts
Summary: The study reveals the complexity of trophoblast lineage emergence using the BAP model, showing distinct characteristics of trophoblast cells under different oxygen conditions. Transcriptomic and cluster analyses suggest potential fusion events and different gene expression patterns in syncytiotrophoblast and cytotrophoblast cells.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Developmental Biology
Bianca Dietrich, Victoria Kunihs, Andreas I. Lackner, Gudrun Meinhardt, Bon-Kyoung Koo, Jurgen Pollheimer, Sandra Haider, Martin Knoefler
Summary: This study reveals that autocrine NOTCH3 signaling controls human placental development by promoting self-renewal of cytotrophoblast progenitors.
Review
Cell Biology
Adam Jaremek, Mariyan J. Jeyarajah, Gargi Jaju Bhattad, Stephen J. Renaud
Summary: Proper development of the placenta, specifically the syncytiotrophoblast, is crucial for successful pregnancy as it regulates the exchange of nutrients and gases between maternal and fetal blood. Dysregulated formation of syncytiotrophoblast can have negative impacts on maternal and fetal health. 'Omics' approaches have been used to gain multidimensional insights into the formation and function of syncytiotrophoblast, but there are still limitations and future avenues for exploration in this area.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Rowan M. Karvas, Laurent David, Thorold W. Theunissen
Summary: Trophoblasts play critical roles in blastocyst implantation and maternal-fetal communication during pregnancy. However, our understanding of human trophoblast biology is limited due to the scarcity of first-trimester placental tissue and the inadequacy of animal models. Recent advancements in deriving human trophoblast stem cells from pluripotent and somatic cell sources provide exciting opportunities to study the molecular mechanisms of placental development and pregnancy-related diseases.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Joanna L. James, Abbey Lissaman, Yohanes N. S. Nursalim, Lawrence W. Chamley
Summary: The use of in vitro tools to study trophoblast differentiation and function is crucial for understanding placental development. Various models including primary trophoblasts, placental explants, stem cell models, and organoid cultures have provided insights into the complex microenvironment and cell-cell crosstalk involved in this process. However, it is important to consider the strengths and limitations of each model and accurately interpret the in vitro data in relation to in vivo aspects of human placentation.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Stephen J. Renaud, Mariyan J. Jeyarajah
Summary: In humans, cell fusion is restricted to only a few cell types under normal conditions. In the placenta, cell fusion is a critical process for generating syncytiotrophoblast and plays a crucial role in ensuring pregnancy health.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Developmental Biology
Yutong Chen, Dylan Siriwardena, Christopher Penfold, Adam Pavlinek, Thorsten E. Boroviak
Summary: This study provides a single-cell atlas of human trophoblast development and performs single-cell profiling of trophoblast stem cells. The study reveals the transcriptional networks of trophoblast lineages and identifies the role of MAPK signaling in cell differentiation. In addition, the study identifies key factors regulating self-renewal of trophoblast stem cells.
Review
Cell Biology
Bum-Kyu Lee, Jonghwan Kim
Summary: Understanding the molecular mechanisms of early human placenta development is crucial for maternal and fetal health. Recent advancements in human trophoblast models offer new opportunities, but the application of high-throughput omics tools in this field remains limited. Integration of omics approaches with human in vitro model systems has the potential to enhance our understanding of placental development and associated complications.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Mariyan J. Jeyarajah, Gargi Jaju Bhattad, Rachel D. Kelly, Kelly J. Baines, Adam Jaremek, Fei-Hung P. Yang, Hiroaki Okae, Takahiro Arima, Vanessa Dumeaux, Stephen J. Renaud
Summary: GCM1 is a critical regulator of both EVT and ST development, affecting cell differentiation and invasive capacity, potentially leading to obstetrical complications such as preeclampsia.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Multidisciplinary Sciences
Mariyan J. Jeyarajah, Gargi Jaju Bhattad, Rachel D. Kelly, Kelly J. Baines, Adam Jaremek, Fei-Hung P. Yang, Hiroaki Okae, Takahiro Arima, Vanessa Dumeaux, Stephen J. Renaud
Summary: GCM1 is a critical regulator of human placenta development, playing a key role in the differentiation and function of EVT and ST. Knockdown of GCM1 hinders TS cell differentiation and impacts their functions in both ST and EVT pathways.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Obstetrics & Gynecology
Zahra Anvar, Imen Chakchouk, Momal Sharif, Sangeetha Mahadevan, Li Su, Swathi Anikar, Fatemeh Alavi Naini, Alloysius Budi Utama, Ignatia B. van den Veyver
Summary: Differentiation of human embryonic stem cells (hESCs) into trophoblast-like cells can be achieved by culturing them in media containing bone morphogenic protein 4 (BMP4). Various media containing BMP4 were compared, and it was found that they differentially drove early differentiation towards trophoblast-like lineages. Each media had its advantages and disadvantages, and selection of a protocol for specific experiments needs to consider these factors.
REPRODUCTIVE SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Rona Karahoda, Sampada Kallol, Michael Groessl, Edgar Ontsouka, Pascale Anderle, Christa Fluck, Frantisek Staud, Christiane Albrecht
Summary: This study investigates the gestational age-dependent changes in the gene expression of key steroidogenic enzymes in human placentas, as well as explores the role of trophoblast cells in steroid biosynthesis and metabolism. The research provides insights into the cellular origin of steroidogenesis in the human placenta and highlights the functional activity of steroidogenic enzymes in primary human trophoblasts.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Junjie Yuan, Kangjing Chen, Wenbo Zhang, Zhucheng Chen
Summary: This study reports the structure of the 12-subunit PBAF complex bound to the nucleosome, revealing the binding mode of SMARCA4 and the functional modularity of PBAF. The findings provide mechanistic insights into nucleosome recognition and a structural basis for understanding SMARCA4-related human diseases.
Article
Cell Biology
Jin Seok, Sujin Jun, Jinki Cho, Sohea Park, Jung Ok Lee, Gi Jin Kim
Summary: The study reveals that PD-MSCs regulate the balance between survival and death of trophoblast cells, protect damaged mitochondria, and enhance trophoblast invasion. These findings suggest that PD-MSCs modulate trophoblast invasion through dynamic effects on mitochondrial energy metabolism.
JOURNAL OF CELLULAR PHYSIOLOGY
(2021)
Article
Multidisciplinary Sciences
Li Wang, Jiali Yu, Zishuo Yu, Qianmin Wang, Wanjun Li, Yulei Ren, Zhenguo Chen, Shuang He, Yanhui Xu
Summary: BAF and PBAF are chromatin remodeling complexes that create nucleosome-depleted regions for transcription activation. This study provides structural insights into PBAF-mediated nucleosome association by reporting the structure of a 13-subunit human PBAF in complex with acetylated nucleosome in ADP-BeF3-bound state.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Christin Naumann, Marcus Heisters, Wolfgang Brandt, Philipp Janitza, Carolin Alfs, Nancy Tang, Alicia Toto Nienguesso, Jorg Ziegler, Richard Imre, Karl Mechtler, Yasin Dagdas, Wolfgang Hoehenwarter, Gary Sawers, Marcel Quint, Steffen Abel
Summary: Access to inorganic phosphate profoundly affects cellular activities and plant performance. This study reveals that Arabidopsis LPR1 acts as a phosphate-dependent cue to adjust root meristem maintenance by sensing subtle concentration differentials of external Fe availability via Fe redox signaling and cell wall modification.
Article
Multidisciplinary Sciences
Christoph Neumayr, Vanja Haberle, Leonid Serebreni, Katharina Karner, Oliver Hendy, Ann Boija, Jonathan E. Henninger, Charles H. Li, Karel Stejskal, Gen Lin, Katharina Bergauer, Michaela Pagani, Martina Rath, Karl Mechtler, Cosmas D. Arnold, Alexander Stark
Summary: This paper investigates different types of enhancers and their reliance on cofactors. The authors find that some enhancers can function without commonly used cofactors, regulating distinct gene regulatory programs.
Article
Oncology
Lukas Leiendecker, Tobias Neumann, Pauline S. Jung, Shona M. Cronin, Thomas L. Steinacker, Alexander Schleiffer, Michael Schutzbier, Karl Mechtler, Thibault Kervarrec, Estelle Laurent, Kamel Bachiri, Etienne Coyaud, Rajmohan Murali, Klaus J. Busam, Babak Itzinger-Monshi, Reinhard Kirnbauer, Lorenzo Cerroni, Eduardo Calonje, Arno Rutten, Frank Stubenrauch, Klaus G. Griewank, Thomas Wiesner, Anna C. Obenauf
Summary: This study reveals the presence of human papillomavirus 42 (HPV42) in 96% of digital papillary adenocarcinoma (DPA), a cancer occurring on fingers and toes. It shows that HPV42, previously considered nononcogenic, behaves similarly to oncogenic, high-risk HPVs. Machine learning analysis indicates that HPV-driven transformation induces a germ cell-like transcriptional program conserved across all HPV-driven cancers, with implications for early detection, diagnosis, and therapy.
Article
Biochemical Research Methods
Sebastian Dorl, Stephan Winkler, Karl Mechtler, Viktoria Dorfer
Summary: Spectral library search enables more sensitive peptide identification in tandem mass spectrometry experiments, but suffers from limited availability of high-quality libraries and the difficulty of creating decoy spectra for result validation. MS Ana is a new spectral library search engine that addresses these issues by allowing the use of curated or predicted libraries and providing robust false discovery control through its own decoy library generation algorithm. In benchmark tests, MS Ana outperformed database search, achieving 36% more spectrum matches and 4% more proteins identified in single-shot human cell-line data. The quality of result validation was demonstrated through tests on synthetic peptide pools, and the importance of library selection was highlighted by comparing the performance of different publicly available human spectral libraries.
JOURNAL OF PROTEOME RESEARCH
(2023)
Article
Multidisciplinary Sciences
Friederike Leesch, Laura Lorenzo-Orts, Carina Pribitzer, Irina Grishkovskaya, Josef Roehsner, Anastasia Chugunova, Manuel Matzinger, Elisabeth Roitinger, Katarina Belacic, Susanne Kandolf, Tzi-Yang Lin, Karl Mechtler, Anton Meinhart, David Haselbach, Andrea Pauli
Summary: Using mass spectrometry and cryo-electron microscopy, the study provides molecular evidence that ribosomes transition from a dormant state to an active state during early embryogenesis. Dormant ribosomes are associated with four conserved factors that stabilize ribosomes and repress translation. Addition of recombinant zebrafish Dap1b protein can block translation and reconstitute the dormant ribosome state in vitro.
Article
Chemistry, Analytical
Manuel Matzinger, Elisabeth Mueller, Gerhard Duernberger, Peter Pichler, Karl Mechtler
Summary: We report a comprehensive workflow that includes improved strategies for all steps, from cell lysis to data analysis. The workflow is easy to implement even for novice users, thanks to the use of convenient-to-handle 1 μL sample volume and standardized 384-well plates. Using advanced micro-pillar columns, ultrashort gradient lengths down to 5 minutes were tested for high throughput. By benchmarking different acquisition methods and data analysis algorithms, the workflow achieved identification of 1790 proteins in a single cell using data-dependent acquisition (DDA), and more than 2200 proteins from single-cell level input using data-independent acquisition (DIA) in a 20-minute active gradient. The workflow also demonstrated its suitability for differentiating two cell lines, indicating its potential for cellular heterogeneity determination.
ANALYTICAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Leonid Serebreni, Lisa-Marie Pleyer, Vanja Haberle, Oliver Hendy, Anna Vlasova, Vincent Loubiere, Filip Nemcko, Katharina Bergauer, Elisabeth Roitinger, Karl Mechtler, Alexander Stark
Summary: Different classes of promoters have distinct mechanisms of transcription initiation, resulting in either focused or dispersed initiation patterns.
Review
Biochemical Research Methods
Manuel Matzinger, Rupert L. Mayer, Karl Mechtler
Summary: Mapping proteomic fingerprints to transcriptomic data is crucial for understanding gene expression and phenotype. Despite challenges in protein amplification and lack of established gold standard workflows, advances in microfluidics, sample separation, data acquisition, and analysis have improved the analysis of tiny sample amounts. Sensitivity, robustness, and throughput are still urgent needs, and label-free single-cell mass spectrometry is a promising strategy for unbiased quantification. This review focuses on recent advances in label-free single-cell mass spectrometry workflows and provides guidance for method selection and future prospects.
Article
Obstetrics & Gynecology
Henrieta Papuchov, Malene Hviid Saxtorph, Trine Hallager, Ida E. Jepsen, Jens O. Eriksen, Gry Persson, Tina Funck, Iben Weisdorf, Nicholas Macklon, Lise Grupe Larsen, Thomas Vauvert F. Hviid
Summary: This study found that genetic polymorphisms of HLA-G and HLA-F can impact recurrent implantation failure. Specific HLA-G promoter haplotypes and 3'UTR haplotypes are associated with reduced fertility, including RIF manifestation, and lower chances of achieving pregnancy, or with an increased risk of experiencing RIF.
REPRODUCTIVE BIOMEDICINE ONLINE
(2023)
Article
Multidisciplinary Sciences
Andreas Lackner, Michael Mueller, Magdalena Gamperl, Delyana Stoeva, Olivia Langmann, Henrieta Papuchova, Elisabeth Roitinger, Gerhard Duernberger, Richard Imre, Karl Mechtler, Paulina A. A. Latos
Summary: The Erf-NCoR1/2 complex controls trophoblast differentiation by linking signalling with transcriptional repression.
NATURE COMMUNICATIONS
(2023)
Article
Biology
Jaydeep Sidhaye, Philipp Trepte, Natalie Sepke, Maria Novatchkova, Michael Schutzbier, Gerhard Duernberger, Karl Mechtler, Juergen A. Knoblich
Summary: By analyzing the transcriptome and epigenome during human corticogenesis, important gene regulatory networks have been identified. Through the use of human brain organoids, specific transcriptome and proteome analyses were conducted, revealing gene expression modules during cortical development. One module involving mTOR-mediated regulation of translation was investigated, showing that partial inhibition of ribosomal genes translation prevents premature translation of differentiation markers, crucial for maintaining the accuracy of cortical development.
Article
Biochemical Research Methods
Micha J. J. Birklbauer, Manuel Matzinger, Fraenze Mueller, Karl Mechtler, Viktoria Dorfer
Summary: In the paper "Cross-linking Mass Spectrometry 2.0", the authors present an updated version of the MS Annika search engine, which accurately identifies cross-linked peptides and introduces a novel scoring function. The evaluation shows that MS Annika 2.0 outperforms other search engines in terms of true unique cross-link detection and false discovery rate estimation.
JOURNAL OF PROTEOME RESEARCH
(2023)
Article
Plant Sciences
Chao Feng, Elisabeth Roitinger, Otto Hudecz, Maria Cuacos, Jana Lorenz, Veit Schubert, Baicui Wang, Rui Wang, Karl Mechtler, Stefan Heckmann
Summary: During meiotic prophase I, the meiotic chromosome axis is essential for synapsis and meiotic recombination progression. TurboID-based proximity labelling enables the identification of proximate proteins in meiotic cells of A. thaliana. This proteomic profiling helps uncover known and new meiotic proteins in rare cell types like meiotic cells.
Article
Multidisciplinary Sciences
Friederike Leesch, Laura Lorenzo-Orts, Carina Pribitzer, Irina Grishkovskaya, Josef Roehsner, Anastasia Chugunova, Manuel Matzinger, Elisabeth Roitinger, Katarina Belacic, Susanne Kandolf, Tzi-Yang Lin, Karl Mechtler, Anton Meinhart, David Haselbach, Andrea Pauli
Summary: Using mass spectrometry and cryo-electron microscopy analyses, we show that ribosomes transition from a dormant state to an active state during the first hours of embryogenesis in zebrafish and Xenopus laevis. Dormant ribosomes are associated with conserved factors that form two modules, responsible for stabilizing ribosomes and repressing translation. A newly discovered translational inhibitor, Dap1b, is found to play a key role in maintaining the dormant state of ribosomes.
