The rostrocaudal (head-to-tail) axis is supplied by populations of progenitors at the caudal end of the embryo. Despite recent advances characterising one of these populations, the neuromesodermal progenitors, their nature and relationship to other populations remains unclear. Here we show that neuromesodermal progenitors are a single Sox2(low)T(low) entity whose choice of neural or mesodermal fate is dictated by their position in the progenitor region. The choice of mesoderm fate is Wnt/β-catenin dependent. Wnt/β-catenin signalling is also required for a previously unrecognised phase of progenitor expansion during mid-trunk formation. Lateral/ventral mesoderm progenitors represent a distinct committed state that is unable to differentiate to neural fates, even upon overexpression of the neural transcription factor Sox2. They do not require Wnt/β-catenin signalling for mesoderm differentiation. This information aids the correct interpretation of in vivo genetic studies and the development of in vitro protocols for generating physiologically-relevant cell populations of clinical interest.
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http://dx.doi.org/10.7554/eLife.10042 | DOI Listing |
Development
January 2025
Department of Genetics, University of Cambridge, Cambridge, UK, CB2 3EH.
Early embryos display a remarkable ability to regulate tissue patterning in response to changes in tissue size. However, it is not clear whether this ability continues into post-gastrulation stages. Here, we performed targeted removal of dorsal progenitors in the zebrafish tailbud using multiphoton ablation.
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December 2024
Center for Cell Lineage Technology and Engineering, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangdong-Hong Kong Joint Laboratory for Stem Cell and Regenerative Medicine, GIBH-CUHK Joint Research Laboratory on Stem Cell and Regenerative Medicine, GIBH-HKU Guangdong-Hong Kong Stem Cell and Regenerative Medicine Research Centre, China-New Zealand Belt and Road Joint Laboratory on Biomedicine and Health, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China. Electronic address:
Single-cell lineage tracing based on CRISPR-Cas9 gene editing enables the simultaneous linkage of cell states and lineage history at a high resolution. Despite its immense potential in resolving the cell fate determination and genealogy within an organism, existing implementations of this technology suffer from limitations in recording capabilities and considerable barcode dropout. Here, we introduce DuTracer, a versatile tool that utilizes two orthogonal gene editing systems to record cell lineage history at single-cell resolution in an inducible manner.
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December 2024
Developmental Biology & Cancer, UCL Great Ormond Street Institute of Child Health, London, United Kingdom.
Methods Mol Biol
November 2024
German Center for Neurodegenerative Diseases e.V. (DZNE), Dresden, Germany.
Many aspects of neurodegenerative disease pathology remain unresolved. Why do certain neuronal subpopulations acquire vulnerability to stress or mutations in ubiquitously expressed genes, while others remain resilient? Do these neurons harbor intrinsic marks that make them prone to degeneration? Do these diseases have a neurodevelopmental component? Lacking this fundamental knowledge hampers the discovery of efficacious treatments. While it is well established that human organoids enable the modeling of brain-related diseases, we still lack an organoid model that recapitulates the regionalization complexity and physiology of the spinal cord.
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November 2024
Department of Cell Biology, Naval Medical University, 200433 Shanghai, China; Shanghai Key Laboratory of Cell Engineering, Naval Medical University, 200433 Shanghai, China. Electronic address:
Progress has been made in generating spinal cord and trunk derivatives from neuromesodermal progenitors (NMPs). However, maintaining the self-renewal of NMPs in vitro remains a challenge. In this study, we developed a cocktail of small molecules and growth factors that induces human embryonic stem cells to produce self-renewing NMPs (srNMPs) under chemically defined conditions.
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