A5001123138- Pluripotent Stem Cells Research
- Developmental Biology and Gene Regulation
- 3D Printing in Biomedical Research
- Neurogenesis and neuroplasticity mechanisms
- Reproductive Biology and Fertility
- Renal and related cancers
- Tissue Engineering and Regenerative Medicine
- Wnt/β-catenin signaling in development and cancer
- Cancer Cells and Metastasis
- Planarian Biology and Electrostimulation
- Nuclear Receptors and Signaling
- Epigenetics and DNA Methylation
- Neuroscience and Neural Engineering
- Skin and Cellular Biology Research
- Cellular Mechanics and Interactions
- Congenital heart defects research
- MicroRNA in disease regulation
The Francis Crick Institute
2021-2024
University of Cambridge
2014-2023
Wellcome/MRC Cambridge Stem Cell Institute
2017-2023
Bridge University
2020
Medical Research Council
2017-2018
Mouse embryonic stem cells (mESCs) are clonal populations derived from preimplantation mouse embryos that can be propagated in vitro and, when placed into blastocysts, contribute to all tissues of the embryo and integrate normal morphogenetic processes, i.e. they pluripotent. However, although steered differentiate cell types organism, cannot organise themselves structures resemble embryos. When aggregated embryoid bodies develop disorganised masses different with little spatial coherence....
The establishment of the anteroposterior (AP) axis is a crucial step during animal embryo development. In mammals, genetic studies have shown that this process relies on signals spatiotemporally deployed in extra-embryonic tissues locate position head and onset gastrulation, marked by T/Brachyury (
The development of the central nervous system is known to result from two sequential events. First, an inductive event mesoderm on overlying ectoderm that generates a neural plate that, after rolling into tube, acts as main source progenitors. Second, axial regionalization will in specification neurons with different anteroposterior identities. Although this description process applies ease amphibians and fish, it more difficult confirm amniote embryos. Here, specialized population cells...
We have developed a protocol improving current Embryoid Body (EB) culture which allows the study of self-organization, symmetry breaking, axial elongation and cell fate specification using aggregates mouse embryonic stem cells (mESCs) in suspension culture. Small numbers mESCs are aggregated basal medium for 48 hr non-tissue-culture-treated, U-bottomed 96-well plates, after they competent to respond experimental signals. Following treatment, these begin show signs polarized gene expression...
Pharmaceuticals intended for use in patients of childbearing potential need to be tested teratogenicity before marketing. Several pharmaceutical companies animal-free vitro models which allow a more rapid selection lead compounds and contribute 3Rs principles (‘replace, reduce refine’) by streamlining the promising submitted further regulatory studies animals. Currently available typically rely on adherent monolayer cultures or disorganized 3D structures, both lack spatiotemporal...
ABSTRACT Primordial germ cells (PGCs) are the early embryonic precursors of gametes – sperm and egg cells. PGC-like (PGCLCs) can currently be derived in vitro from pluripotent exposed to signalling cocktails aggregated into large bodies, but these do not recapitulate native environment during PGC formation. Here, we show that mouse gastruloids, a three-dimensional model gastrulation, contain population gastruloid-derived PGCLCs (Gld-PGCLCs) resemble PGCs vivo. Importantly, conserved...
The mammalian embryos Caudal Lateral Epiblast harbours bipotent progenitors that contribute to the spinal cord and paraxial mesoderm in concert with body axis elongation. These progenitors, called Neural Mesodermal Progenitors (NMPs) are identified as cells coexpressing Sox2 T/Brachyury, a criterion used derive NMP-like from embryonic stem vitro. However, these do not self renew, NMPs do. Here we find protocols yield vitro first produce multipotent population that, addition NMPs, generate...
Abstract Many amniote vertebrate species including humans can form identical twins from a single embryo, but this only occurs rarely. It has been suggested that the primitive-streak-forming embryonic region emits signals inhibit streak formation elsewhere involved, how they are transmitted and act not elucidated. Here we show short tracks of calcium firing activity propagate through extraembryonic tissue via gap junctions prevent ectopic primitive in chick embryos. Cross-regulation an...
Abstract Dissociated mouse embryonic stem (ES) cells were cultured to form aggregates in small volumes of basal medium U-bottomed, non tissue-culture-treated 96-well plates and subsequently maintained suspension culture. After growth for 48 hours, the are competent respond ubiquitous experimental signals which result their symmetry-breaking generation defined polarised structures by 96 hours. It is envisaged that this system can be applied both study early developmental events more broadly...
Abstract The Caudal Lateral Epiblast of mammalian embryos harbours bipotent progenitors that contribute to the spinal cord and paraxial mesoderm in concert with elongation body axis. These progenitors, called Neural Mesodermal Progenitors (NMPs) are identified as cells coexpressing Sox2 T/Brachyury , a criterion used derive NMP-like from Embryonic Stem Cells vitro. However, these do not self renew, embryonic NMPs do. Here we find protocols yield vitro first produce multipotent population...
Abstract Generation of asymmetry within the early embryo is a critical step in establishment three body axes, providing reference for patterning organism. To study and development anteroposterior axis (AP) culture, we utilised our ‘ Gastruloid ’ model system. Gastruloids ’, highly reproducible embryonic organoids formed from aggregates mouse stem cells, display symmetry-breaking, polarised gene expression axial development, mirroring processes on time-scale similar to that embyro. Using ESCs...
Abstract Establishment of the three body axes is a critical step during animal development. In mammals, genetic studies have shown that combination precisely deployed signals from extraembryonic tissues position anteroposterior axis (AP) within embryo and lead to emergence dorsoventral (DV) left-right (LR) axes. We used Gastruloids , embryonic organoids, as model system understand this process find they are able develop AP, DV LR well undergo axial elongation in manner mirror embryos. The...
Neuromesodermal progenitors (NMps) are a population of bipotent that maintain competence to generate both spinal cord and paraxial mesoderm throughout the elongation posterior body axis. Recent studies have generated populations NMp-like cells in culture, which been shown differentiate neural mesodermal cell fates when transplanted into either mouse or chick embryos. Here, we aim compare potential embryonic stem (ES) cell-derived progenitor NMp behaviour against undifferentiated...
Human stem cell-based embryo models have opened new avenues of research in development by providing experimentally amenable vitro systems. One the features is their multilineage differentiation, which allows co-development of, and interactions between, tissues. Here, we utilise a human Trunk-like Structure (hTLS) model to explore trunk development. We show that hTLS morphologically organised somites neural tube form through self-organised, endogenous signalling including anteroposterior FGF,...
We have developed a protocol improving current Embryoid Body (EB) culture which allows the study of self-organization, symmetry breaking, axial elongation and cell fate specification using aggregates mouse embryonic stem cells (mESCs) in suspension culture. Small numbers mESCs are aggregated basal medium for 48 hr non-tissue-culture-treated, U-bottomed 96-well plates, after they competent to respond experimental signals. Following treatment, these begin show signs polarized gene expression...
Abstract Pharmaceuticals that are intended for use in patients of childbearing potential need to be tested teratogenicity before marketing. Several pharmaceutical companies animal-free vitro models which allow a more rapid selection lead compounds and contribute 3Rs principles (‘replace, reduce refine’) by streamlining the promising submitted further regulatory studies animals. Currently available typically rely on adherent monolayer cultures or disorganized 3D structures, both lack...
Abstract Neuromesodermal progenitors (NMps) are a population of bipotent that maintain competence to generate both spinal cord and paraxial mesoderm throughout the elongation posterior body axis. Recent studies have generated populations NMp-like cells in culture been shown differentiate neural mesodermal cell fates when transplanted into either mouse or chick embryos. Here, we aim compare potential embryonic stem (ES) cell-derived progenitor NMp behavior against undifferentiated...