A5002485710- Pluripotent Stem Cells Research
- Developmental Biology and Gene Regulation
- Gene Regulatory Network Analysis
- Cellular Mechanics and Interactions
- Genetics, Aging, and Longevity in Model Organisms
- 3D Printing in Biomedical Research
- Planarian Biology and Electrostimulation
- Microtubule and mitosis dynamics
- Renal and related cancers
- RNA Research and Splicing
- CRISPR and Genetic Engineering
- Photoreceptor and optogenetics research
- Early Childhood Education and Development
- Circadian rhythm and melatonin
- Protein Kinase Regulation and GTPase Signaling
- Kruppel-like factors research
- Plant Molecular Biology Research
- Melanoma and MAPK Pathways
- Micro and Nano Robotics
- Genomics and Chromatin Dynamics
- Congenital heart defects research
- Spaceflight effects on biology
- Genomics, phytochemicals, and oxidative stress
- Wnt/β-catenin signaling in development and cancer
- Cognitive Abilities and Testing
European Molecular Biology Laboratory
2019-2025
TU Dresden
2023-2025
Max Planck Institute of Molecular Cell Biology and Genetics
2024
RIKEN Center for Biosystems Dynamics Research
2018-2022
Quantitative Biology Center
2017
Kyoto University
2004-2015
Japan Science and Technology Agency
2012-2015
RIKEN Center for Computational Science
2015
Although mechanisms of embryonic development are similar between mice and humans, the time scale is generally slower in humans. To investigate these interspecies differences development, we recapitulate murine human segmentation clocks that display 2- to 3-hour 5- 6-hour oscillation periods, respectively. Our genome-swapping analyses indicate period difference not due sequence HES7 locus, core gene clock. Instead, demonstrate multiple biochemical reactions HES7, including degradation...
Abstract During embryonic development, epithelial cell blocks called somites are periodically formed according to the segmentation clock, becoming foundation for segmental pattern of vertebral column. The process somitogenesis has recently been recapitulated with murine and human pluripotent stem cells. However, an in vitro model coupled clock epithelialization is still missing. Here, we report generation somitoids, organoids that form pairs somite-like structures. Somitoids display clear...
Differential speeds in biochemical reactions have been proposed to be responsible for the differences developmental tempo between mice and humans. However, underlying mechanism controlling species-specific kinetics remains determined. Using vitro differentiation of pluripotent stem cells, we recapitulated segmentation clocks diverse mammalian species varying body weight taxa: marmoset, rabbit, cattle, rhinoceros. Together with mouse human, clock periods six did not scale animal weight, but...
ERK MAP kinase signaling plays a pivotal role in diverse cellular functions, including cell proliferation, differentiation, migration and survival. One of the central questions concerning this is how activation same protein kinase, ERK, elicits distinct outcomes. Recent progress has demonstrated that differences duration, magnitude subcellular compartmentalization activity generate variations output regulate fate decisions. Furthermore, several molecules have been identified as spatial,...
Intermittent fasting is one of the most effective dietary restriction regimens that extend life span in C. elegans and mammals. Fasting-stimulus responses are key to longevity response; however, mechanisms sense transduce stimulus remain largely unknown. Through a comprehensive transcriptome analysis elegans, we find along with FOXO transcription factor DAF-16, AP-1 (JUN-1/FOS-1) plays central role fasting-induced transcriptional changes. KGB-1, JNKs, acts as an activator activated response...
Abstract A synthetic mammalian reaction-diffusion pattern has yet to be created, and Nodal-Lefty signaling been proposed meet conditions for formation: Nodal is a short-range activator whereas Lefty long-range inhibitor. However, this forming possibility never directly tested, the underlying mechanisms of differential diffusivity remain unclear. Here, through combination theoretical approaches, we show that reconstituted network in cells spontaneously gives rise pattern. Surprisingly,...
The emerging field of synthetic developmental biology proposes bottom-up approaches to examine the contribution each cellular process complex morphogenesis. However, shortage tools manipulate three-dimensional (3D) shapes mammalian tissues hinders progress field. Here we report development OptoShroom3, an optogenetic tool that achieves fast spatiotemporal control apical constriction in epithelia. Activation OptoShroom3 through illumination epithelial Madin-Darby Canine Kidney (MDCK) cell...
Nuclear export of mRNA is an essential process for eukaryotic gene expression. The TREX complex couples expression from transcription and splicing to export. Sub2, a core component the in yeast, has diversified humans two closely related RNA helicases, UAP56 URH49. Here, we show that URH49 forms novel URH49-CIP29 complex, termed AREX (alternative export) whereas human complex. mRNAs regulated by these helicases are different at genome-wide level. sets target contain distinct subsets key...
Cell-type diversity in multicellular organisms is created through a series of binary cell fate decisions. Lateral inhibition controlled by Delta-Notch signalling the core mechanism for choice alternative types homogeneous neighbouring cells. Here, we show that cells engineered with Delta-Notch-dependent lateral circuit spontaneously bifurcate into Delta-positive and Notch-active populations. The synthetic comprises transcriptional repression Delta intracellular feedback Lunatic fringe...
The actin cytoskeleton undergoes rapid changes in its architecture during mitosis. Here, we demonstrate novel assembly dynamics M phase. An amorphous cluster of filaments appears prometaphase, revolves horizontally along the cell cortex at a constant angular speed, and fuses into contractile ring after three to four revolutions. Cdk1 activity is required for formation this mitotic revolving movement. Rapid turnover takes place everywhere also rotation Knockdown Arp3, component...
Despite the growing evidence for regulated spindle orientation in mammals, a systematic approach identifying responsible genes mammalian cells has not been established. Here we perform kinase-targeting RNAi screen HeLa and identify ABL1 as novel regulator of orientation. Knockdown causes cortical accumulation Leu-Gly-Asn repeat-enriched-protein (LGN), an evolutionarily conserved This results LGN-dependent rotation misorientation. In vivo inactivation by pharmacological inhibitor or ablation...
Spermatogonial stem cells (SSCs) present the potential to acquire pluripotency under specific culture conditions. However, frequency of pluripotent cell derivation is low, and mechanism SSC reprogramming remains unknown. In this study, we report that induction global DNA hypomethylation in germline (GS) (cultured SSCs) induces derivation. When demethylation was triggered by Dnmt1 depletion, GS underwent apoptosis. were converted into embryonic (ES)-like double knockdown p53. This treatment...
Multicellular aggregates are known to exhibit liquid-like properties. The fusion process of two cell is commonly studied as the coalescence viscous drops. However, tissues complex materials and can viscoelastic behaviour. It that elastic effects prevent complete drops, a phenomenon arrested coalescence. Here we study this in stem provide theoretical framework which agrees with experiments. In addition, agent-based simulations show active fluctuations control solid-to-fluid phase transition,...
Abstract Human embryonic development is generally slower compared with mouse, and one of the model systems for such inter-species differences in developmental tempo segmentation clock. The oscillation period human clock, as measured induced presomitic mesoderm (iPSM) cells, two times longer than that mouse. While core clock gene HES7 known to show protein degradation iPSM mouse iPSM, it remains unclear whether concept species-specific stability generalizable other genes. Here we...
Abstract Numerous cellular and molecular processes during embryonic development prompt the fundamental question of how their tempos are coordinated whether a common global modulator exists. While segmentation clock tempo scales with kinetics gene expression degradation core Hes7 across mammals, coordination these remains unclear. This study examines metabolic activities serve as for clock, finding them to be selective instead. Several inhibitions extend period but affect key differently:...
An engineered system based on Notch and Delta in mammalian cultured cells recapitulates signal propagation, a phenomenon that occurs development.