A5037585395- Telomeres, Telomerase, and Senescence
- Developmental Biology and Gene Regulation
- Neurogenesis and neuroplasticity mechanisms
- Tissue Engineering and Regenerative Medicine
- Congenital heart defects research
- Genetics, Aging, and Longevity in Model Organisms
- Nerve injury and regeneration
- Single-cell and spatial transcriptomics
- Congenital limb and hand anomalies
- RNA Research and Splicing
- Axon Guidance and Neuronal Signaling
- Proteoglycans and glycosaminoglycans research
- Renal and related cancers
- Prenatal Screening and Diagnostics
- Bone Metabolism and Diseases
- Tree Root and Stability Studies
- Connective tissue disorders research
- interferon and immune responses
- Dietary Effects on Health
- Skin and Cellular Biology Research
- Electrospun Nanofibers in Biomedical Applications
- Pluripotent Stem Cells Research
- Cell Adhesion Molecules Research
- Biomedical and Engineering Education
- MicroRNA in disease regulation
Stem Cell Institute
2024
Wellcome/MRC Cambridge Stem Cell Institute
2021-2023
University of Cambridge
2021-2023
Hospital for Sick Children
2016-2022
Great Ormond Street Hospital
2020
University College London
2020
SickKids Foundation
2020
Barcelona Institute for Science and Technology
2017
Institute of Science and Technology
2017
Universitat Pompeu Fabra
2012-2017
Senescence is a form of cell cycle arrest induced by stress such as DNA damage and oncogenes. However, while arrested, senescent cells secrete variety proteins collectively known the senescence-associated secretory phenotype (SASP), which can reinforce induce senescence in paracrine manner. SASP has also been shown to favor embryonic development, wound healing, even tumor growth, suggesting more complex physiological roles than currently understood. Here we uncover timely new functions...
Alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV) is a rare, neonatally lethal developmental disorder the lung defining histologic abnormalities typically associated multiple congenital anomalies (MCA). Using array CGH analysis, we have identified six overlapping microdeletions encompassing FOX transcription factor gene cluster in chromosome 16q24.1q24.2 patients ACD/MPV and MCA. Subsequently, four different heterozygous mutations (frameshift, nonsense, no-stop)...
Abstract Human limbs emerge during the fourth post-conception week as mesenchymal buds, which develop into fully formed over subsequent months 1 . This process is orchestrated by numerous temporally and spatially restricted gene expression programmes, making congenital alterations in phenotype common 2 Decades of work with model organisms have defined fundamental mechanisms underlying vertebrate limb development, but an in-depth characterization this humans has yet to be performed. Here we...
Altered stem cell homeostasis is linked to organismal aging. However, the mechanisms involved remain poorly understood. Here we report novel alterations in hair follicle cells during skin aging, including increased numbers, decreased function, and an inability tolerate stress. Performing high-throughput RNA sequencing on aging cells, cytokine arrays, functional assays, identify age-associated imbalance epidermal Jak–Stat signaling that inhibits function. Collectively, this study reveals a...
<h3>Background</h3> Congenital malformations involving the Müllerian ducts are observed in around 5% of infertile women. Complete aplasia uterus, cervix, and upper vagina, also termed or Mayer–Rokitansky–Kuster–Hauser (MRKH) syndrome, occurs with an incidence 1 4500 female births, both isolated syndromic forms. Previous reports have suggested that a proportion cases, especially caused by variation copy number at different genomic loci. <h3>Methods</h3> In order to obtain overview...
Circulating systemic factors can regulate adult neural stem cell (NSC) biology, but the identity of these circulating cues is still being defined. Here, we have focused on cytokine interleukin-6 (IL-6), since increased levels IL-6 are associated with pathologies such as autism and bipolar disorder. We show that promotes proliferation post-natal murine forebrain NSCs that, when receptor inducibly knocked out in or precursors, this causes a long-term decrease NSCs. Moreover, transient surge...
Abstract Peripheral nerves provide a supportive growth environment for developing and regenerating axons are essential maintenance repair of many non-neural tissues. This capacity has largely been ascribed to paracrine factors secreted by nerve-resident Schwann cells. Here, we used single-cell transcriptional profiling identify ligands made different injured rodent nerve cell types have combined this with cell-surface mass spectrometry computationally model potential interactions peripheral...
Significance Multipotent Schwann cell precursors (SCPs) generate numerous types. Here, in both mouse and zebrafish, SCPs contributed to the generation of mesenchymal, chondroprogenitor, osteoprogenitor cells during embryonic development. These findings reveal a source cartilage bone previously unanticipated interactions between nervous system skeleton
Digit tip regeneration is one of the few examples true multi-tissue in an adult mammal. The key step this process formation blastema, a transient proliferating cell mass that generates different types digit to replicate original structure. Failure form blastema results lack and has been postulated be reason why mammalian limbs cannot regrow following amputation. Understanding how forms functions will help us determine what required for occur provide insights into potential therapies tissue...
Here, we ask why the nail base is essential for mammalian digit tip regeneration, focusing on inductive mesenchyme. We identify a transcriptional signature these cells that includes Lmx1b and show Lmx1b-expressing mesenchyme blastema formation. use combination of Lmx1bCreERT2-based lineage-tracing single-cell analyses to contributes two pro-regenerative mechanisms. One group maintains their identity regenerates new A second specifically dorsal blastema, loses phenotype, acquires state highly...
Abstract Human limbs emerge during the fourth post-conception week as mesenchymal buds which develop into fully-formed over subsequent months. Limb development is orchestrated by numerous temporally and spatially restricted gene expression programmes, making congenital alterations in phenotype common. Decades of work with model organisms has outlined fundamental processes underlying vertebrate limb development, but an in-depth characterisation this process humans yet to be performed. Here we...
Cellular senescence is an irreversible form of cell cycle arrest that has been linked to several pathological conditions. In particular, can function as a tumor suppressor mechanism, but also thought contribute organismal aging. Paradoxically however, through the secretion various factors, collectively termed senescence-associated secretory phenotype (SASP), senescent cells have tumor-promoting and tissue-remodeling functions. addition, play beneficial roles in tissue repair wound healing,...
Abstract Tissue regeneration is a dynamic process requiring coordinated cell fate decisions to restore structure and function. For instance, the tips of human rodent digits fully regrow after amputation, although more proximal injuries fail regenerate. While biochemical cues have been widely studied in wound healing, role physical microenvironment remains less understood. Here, we discovered that tissue mechanics extracellular matrix (ECM) composition differ markedly between non-regenerating...