Transcriptional networks, regulated by extracellular signals, control cell fate decisions and determine the size and composition of developing tissues. One example is the network controlling bipotent neuromesodermal progenitors (NMPs) that fuel embryo elongation by generating spinal cord and trunk mesoderm tissue. Here, we use single-cell transcriptomics to identify the molecular signature of NMPs and reverse engineer the mechanism that regulates their differentiation. Together with genetic perturbations, this reveals a transcriptional network that integrates opposing retinoic acid (RA) and Wnt signals to determine the rate at which cells enter and exit the NMP state. RA, produced by newly generated mesodermal cells, provides feedback that initiates NMP generation and induces neural differentiation, thereby coordinating the production of neural and mesodermal tissue. Together, the data define a regulatory network architecture that balances the generation of different cell types from bipotential progenitors in order to facilitate orderly axis elongation.
Neural differentiation, selection and transcriptomic profiling of human neuromesodermal progenitor-like cells in vitro.
Myc activity is required for maintenance of the neuromesodermal progenitor signalling network and for segmentation clock gene oscillations in mouse.
Lineage tracing of axial progenitors using Nkx1-2CreERT2 mice defines their trunk and tail contributions.
Inference of Developmental Gene Regulatory Networks Beyond Classical Model Systems: New Approaches in the Post-genomic Era
Transcriptionally dynamic progenitor populations organised around a stable niche drive axial patterning
Neuro-mesodermal progenitors (NMPs): a comparative study between pluripotent stem cells and embryo-derived populations
Regulating Retinoic Acid Availability during Development and Regeneration: The Role of the CYP26 Enzymes
A dorsal-ventral gradient of Wnt3a/β-catenin signals controls mouse hindgut extension and colon formation.
Discovery of genes required for body axis and limb formation by global identification of retinoic acid-regulated epigenetic marks.
How do signaling and transcription factors regulate both axis elongation and Hox gene expression along the anteroposterior axis?
Modeling human somite development and fibrodysplasia ossificans progressiva with induced pluripotent stem cells
Sall4 regulates neuromesodermal progenitors and their descendants during body elongation in mouse embryos
New Insights into the Control of Cell Fate Choices and Differentiation by Retinoic Acid in Cranial, Axial and Caudal Structures
Eomes and Brachyury control pluripotency exit and germ-layer segregation by changing the chromatin state
Sox2 and Canonical Wnt Signaling Interact to Activate a Developmental Checkpoint Coordinating Morphogenesis with Mesoderm Fate Acquisition.
Hox13 genes are required for mesoderm formation and axis elongation during early zebrafish development
Mouse gastrulation: Coordination of tissue patterning, specification and diversification of cell fate
Defining the signalling determinants of a posterior ventral spinal cord identity in human neuromesodermal progenitor derivatives.
Dynamic extrinsic pacing of the HOX clock in human axial progenitors controls motor neuron subtype specification.
Spatiotemporal contribution of neuromesodermal progenitor-derived neural cells in the elongation of developing mouse spinal cord.
What fuels the fly: Energy metabolism in Drosophila and its application to the study of obesity and diabetes.
Adult Stem Cells
Adult stem cells reside in unique niches that provide vital cues for their survival, self-renewal, and differentiation. They hold great promise for use in tissue repair and regeneration as a novel therapeutic strategies. Here is the latest research.