A5089100040- Pluripotent Stem Cells Research
- Renal and related cancers
- CRISPR and Genetic Engineering
- Reproductive Biology and Fertility
- Single-cell and spatial transcriptomics
- Tissue Engineering and Regenerative Medicine
- Animal Genetics and Reproduction
- Epigenetics and DNA Methylation
- Congenital heart defects research
- Biomedical Ethics and Regulation
- Prenatal Screening and Diagnostics
- Hippo pathway signaling and YAP/TAZ
- Cell Image Analysis Techniques
- Gene Regulatory Network Analysis
- Immunodeficiency and Autoimmune Disorders
- Autism Spectrum Disorder Research
- Neonatal Respiratory Health Research
- Metabolism and Genetic Disorders
- Sexual Differentiation and Disorders
- Mesenchymal stem cell research
- Cancer Genomics and Diagnostics
- Mitochondrial Function and Pathology
- Birth, Development, and Health
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Genetics and Neurodevelopmental Disorders
University of Cambridge
2011-2025
The Francis Crick Institute
2016-2025
Wellcome/MRC Cambridge Stem Cell Institute
2012-2025
Medical Research Council
2023-2025
Babraham Institute
2023-2025
Stem Cell Institute
2023-2024
Wellcome Trust
2024
Transnational Press London
2024
Anna Needs Neuroblastoma Answers
2016
King's College London
2016
The generation of pluripotent stem cells from an individual patient would enable the large-scale production cell types affected by that patient's disease. These could in turn be used for disease modeling, drug discovery, and eventually autologous replacement therapies. Although recent studies have demonstrated reprogramming human fibroblasts to a state, it remains unclear whether these induced (iPS) can produced directly elderly patients with chronic We generated iPS 82-year-old woman...
Here we provide fundamental insights into early human development by single-cell RNA-sequencing of and mouse preimplantation embryos. We elucidate conserved transcriptional programs along with those that are human-specific. Importantly, validate our findings at the protein level, which further reveals differences in embryo gene expression. For example, identify several genes exclusively expressed pluripotent epiblast including transcription factor KLF17. Key components TGF-β signaling...
BMP is thought to induce hESC differentiation toward multiple lineages including mesoderm and trophoblast. The BMP-induced trophoblast phenotype a long-standing paradox in stem cell biology. Here we readdressed function hESCs mouse epiblast-derived cells. We found that BMP4 cooperates with FGF2 (via ERK) inhibit endoderm differentiation. These conditions induced cells high levels of BRACHYURY (BRA) coexpressed CDX2. BRA was necessary for preceded CDX2 expression; both genes were essential...
In embryonic stem (ES) cells, a well-characterized transcriptional network promotes pluripotency and represses gene expression required for differentiation. comparison, the networks that promote differentiation of ES cells blastocyst inner cell mass are poorly understood. Here, we show Sox17 is regulator in these pluripotent cells. deficient fail to differentiate into extraembryonic types maintain pluripotency-associated transcription factors, including Oct4 , Nanog Sox2 . contrast, forced...
CRISPR-Cas9 genome editing is a promising technique for clinical applications, such as the correction of disease-associated alleles in somatic cells. The use this approach has also been discussed context heritable human germ line. However, studies assessing gene early embryos report low efficiency mutation repair, high rates mosaicism, and possibility unintended outcomes that may have pathologic consequences. We developed computational pipelines to assess single-cell genomics transcriptomics...
Transcription factor-mediated reprograming is a powerful method to study cell fate changes. In this study, we demonstrate that the transcription factor Gata6 can initiate of multiple types induced extraembryonic endoderm stem (iXEN) cells. Intriguingly, sufficient drive iXEN cells from mouse pluripotent and differentiated neural Furthermore, GATA6 induction in human embryonic (hES) also down-regulates pluripotency gene expression up-regulates (ExEn) genes, revealing conserved function...
Meiotic synapsis and recombination ensure correct homologous segregation genetic diversity. Asynapsed homologs are transcriptionally inactivated by meiotic silencing, which serves a surveillance function in males drives sex chromosome inactivation. Silencing depends on the DNA damage response (DDR) network, but how DDR proteins engage repressive chromatin marks is unknown. We identify histone H3-lysine-9 methyltransferase SETDB1 as bridge linking to silencing male mice. At onset of X H3K9...
Our understanding of the molecular events driving cell specification in early mammalian development relies mainly on mouse studies, and it remains unclear whether these mechanisms are conserved across mammals, including humans. We have shown that establishment polarity via aPKC is a event initiation trophectoderm (TE) placental programme mouse, cow human embryos. However, transducing into fate embryos unknown. Here, we examined evolutionary conservation Hippo signalling, which thought to...
Abstract STUDY QUESTION Which processes and transcription factors specify the first second lineage segregation events during human preimplantation development? SUMMARY ANSWER Differentiation into trophectoderm (TE) cells can be initiated independently of polarity; moreover, TEAD1 YAP1 co-localize in (precursor) TE primitive endoderm (PrE) cells, suggesting a role both events. WHAT IS KNOWN ALREADY We know that polarity, YAP1/GATA3 signalling phospholipase C play key initiation compacted...
Abstract Genetic variants linked to autism are thought change cognition and behaviour by altering the structure function of brain. Although a substantial body literature has identified structural brain differences in autism, it is unknown whether autism-associated common genetic changes cortical macro- micro-structure. We investigated this using neuroimaging data from adults (UK Biobank, N = 31,748) children (ABCD, 4928). Using polygenic scores correlations we observe robust negative...
The inner cell mass of the mouse pre-implantation blastocyst comprises epiblast progenitor and primitive endoderm cells which cognate embryonic (mESCs) or extra-embryonic (XEN) stem lines can be derived. Importantly, each type retains defining properties lineage restriction their in vivo tissue origin. Recently, we demonstrated that XEN-like arise within mESC cultures. This raises possibility mESCs generate self-renewing XEN without requirement for gene manipulation. We have developed a...