A5056287390- Neurogenesis and neuroplasticity mechanisms
- Pluripotent Stem Cells Research
- Epigenetics and DNA Methylation
- Genetics and Neurodevelopmental Disorders
- MicroRNA in disease regulation
- Mesenchymal stem cell research
- Nerve injury and regeneration
- RNA Research and Splicing
- Developmental Biology and Gene Regulation
- Dietary Effects on Health
- RNA Interference and Gene Delivery
- Single-cell and spatial transcriptomics
- Genomics and Chromatin Dynamics
- Telomeres, Telomerase, and Senescence
- Circadian rhythm and melatonin
- Wnt/β-catenin signaling in development and cancer
- Genetics, Aging, and Longevity in Model Organisms
- Genetic Neurodegenerative Diseases
- Axon Guidance and Neuronal Signaling
- TGF-β signaling in diseases
- 14-3-3 protein interactions
- Liver physiology and pathology
- Biomedical and Engineering Education
- Alzheimer's disease research and treatments
- Microtubule and mitosis dynamics
Institute of Molecular Biotechnology
2018-2023
Austrian Academy of Sciences
2019-2023
Vienna Biocenter
2018-2022
The Francis Crick Institute
2013-2021
Consorci Institut D'Investigacions Biomediques August Pi I Sunyer
2006-2011
Universitat de Barcelona
2006-2011
Biomedical Research Networking Center on Neurodegenerative Diseases
2009-2011
Sending neural stem cells back to the garage In brain's hippocampus, which modulates memories and emotions, generate new neurons, even during adulthood. How many neurons are generated, when, follows from balance between quiescence proliferation in pool of cells. Urbán et al. asked what signals send proliferating into a quiescent state. They found that key transcription factor promotes cellular was degraded through ubiquitinylation system. This molecular interaction regulated return resting...
The majority of neural stem cells (NSCs) in the adult brain are quiescent, and this fraction increases with aging. Although signaling pathways that promote NSC quiescence have been identified, transcriptional mechanisms involved mostly unknown, largely due to lack a cell culture model. In study, we first demonstrate cultures (NS cells) exposed BMP4 acquire cellular characteristics quiescent cells. We then use epigenomic profiling identify enhancers associated NS state. Motif enrichment...
The activity of adult stem cells is regulated by signals emanating from the surrounding tissue. Many niche have been identified, but it unclear how they influence choice to remain quiescent or divide. Here we show that when hippocampus receive activating signals, first induce expression transcription factor Ascl1 and only subsequently exit quiescence. Moreover, lowering reduces proliferation rate hippocampal cells, inactivating blocks quiescence completely, rendering them unresponsive...
Neural stem cell numbers fall rapidly in the hippocampus of juvenile mice but stabilize during adulthood, ensuring lifelong hippocampal neurogenesis. We show that this stabilization young adults is result coordinated changes behavior. Although proliferating neural cells juveniles differentiate rapidly, they increasingly return to a resting state shallow quiescence and progress through additional self-renewing divisions adulthood. Single-cell transcriptomics, modeling, label retention...
Quiescence is essential for the long-term maintenance of adult stem cells but how maintain quiescence poorly understood. Here, we show that neural (NSCs) in mouse hippocampus actively transcribe pro-activation factor Ascl1 regardless their activated or quiescent states. We found inhibitor DNA binding protein Id4 enriched NSCs and elimination results abnormal accumulation premature cell activation. Accordingly, other Id proteins promote NSC cultures. sequesters heterodimerization partner E47,...
Mutations in NIPBL are the most frequent cause of Cornelia de Lange syndrome (CdLS), a developmental disorder encompassing several neurological defects, including intellectual disability and seizures. How mutations affect brain development is not understood. Here we identify Nipbl as functional interaction partner neural transcription factor Zfp609 development. Depletion or from cortical progenitors vivo detrimental to neuronal migration. overlap at genomic binding sites independently...
Throughout life, adult neural stem cells (NSCs) produce new neurons and glia that contribute to crucial brain functions. Quiescence is an essential protective feature of NSCs; however, the establishment maintenance this state remain poorly understood. We demonstrate in zebrafish pallium, brain-enriched miR-9 expressed exclusively a subset quiescent NSCs, highlighting heterogeneity within these cells, necessary maintain NSC quiescence. Strikingly, miR-9, along with Argonaute proteins (Agos),...
Adult mouse hippocampal neural stem cells (NSCs) generate new neurons that integrate into existing networks and modulate mood memory. These NSCs are largely quiescent stimulated by niche signals to activate produce neurons. Wnt/β-catenin signalling acts at different steps along the neurogenic lineage, but whether it has a direct role in regulation of remains unclear. Here, we used reporters transcriptomic data from vivo vitro models show adult respond signalling. stimulation instructed...
Abstract During central nervous system development, several transcription factors regulate the differentiation of progenitor cells to postmitotic neurons. Here we describe a novel role for Ikaros‐1 in generation late‐born striatal Our results show that is expressed boundary germinal zone (GZ)/mantle (MZ), where it induces cell cycle arrest neural progenitors by up‐regulation cyclin‐dependent kinase inhibitor (CDKi) p21 Cip1/Waf1 . This effect coupled with neuronal late precursors, which turn...
Development of the nervous system is finely regulated by consecutive expression cell-specific transcription factors. Here we show that Helios, a member Ikaros factor family, expressed in ectodermal and neuroectodermal-derived tissues. During embryonic development, Helios several brain structures including lateral ganglionic eminence (LGE, striatal anlage); cingulated, insular retrosplenial cortex; hippocampus; accessory olfactory bulb. Moreover, also Purkinje neurons during postnatal...
The majority of adult neural stem cells (aNSCs) are in a distinct metabolic state reversible cell cycle exit also known as quiescence. rate aNSC activation determines the number new neurons generated and directly influences long-term maintenance neurogenesis. Despite its relevance, it is still unclear how quiescence regulated. Many factors contribute to this, like heterogeneity, lack reliable markers, complexity neurogenic niches or intricacy transcriptional post-transcriptional mechanisms...
Abstract Background Nolz1 is a zinc finger transcription factor whose expression enriched in the lateral ganglionic eminence (LGE), although its function still unknown. Results Here we analyze role of during LGE development. We show that high proliferating neural progenitor cells (NPCs) subventricular zone. In addition, low levels are detected mantle zone, as well adult striatum. Similarly, highly expressed LGE-derived NPC cultures, but rapidly decrease upon cell differentiation, pointing to...
Abstract Embryonic stem (ES) cells have great potential for cell replacement in neurodegenerative disorders. Implantation of these into the brain, however, requires their prior differentiation. We examined interplay between leukemia inhibitory factor (LIF) and retinoic acid (RA) on neural differentiation mouse ES (mES) cells. Mouse embryonic were allowed to form aggregates, so‐called embryoid bodies (EBs), absence or presence LIF. In LIF, mES downregulated expression undifferentiated marker...
Intermittent fasting (IF) is a promising strategy to counteract ageing shown increase the number of adult-born neurons in dentate gyrus mice. However, it unclear which steps adult neurogenesis process are regulated by IF. The neural stem cells (NSCs) decreases with age an activation-dependent manner and, this loss, NSCs found quiescent state ensures their long-term maintenance. We aimed determine if and how IF affects hippocampus. To identify effects every-other-day on all following...
SUMMARY Neural stem cell numbers fall rapidly in the hippocampus of juvenile mice but stabilise during adulthood, ensuring lifelong hippocampal neurogenesis. We show that this reduction depletion rate is result multiple coordinated changes behaviour. In particular, while active neural cells divide only once or twice before differentiating juveniles, they increasingly return to a resting state shallow quiescence and progress through additional self-renewing divisions adulthood. Single-cell...
SUMMARY Quiescence is essential for the long-term maintenance of adult stem cells and tissue homeostasis. However, how maintain quiescence still poorly understood. Here we show that in dentate gyrus hippocampus actively transcribe pro-activation factor Ascl1 regardless their activation state. We found inhibitor DNA binding protein Id4 suppresses activity neural cell cultures. sequesters heterodimerisation partner E47, promoting degradation quiescence. Accordingly, elimination from results...