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Reconstructing axial progenitor field dynamics in mouse stem cell-derived embryoids

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Bolondi,  Adriano       
Dept. of Genome Regulation (Head: Alexander Meissner), Max Planck Institute for Molecular Genetics, Max Planck Society;

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Kretzmer,  Helene       
Computational Genomics (Helene Kretzmer), Dept. of Genome Regulation (Head: Alexander Meissner), Max Planck Institute for Molecular Genetics, Max Planck Society;

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Gassaloglu,  Seher Ipek
Stem Cell Chromatin (Aydan Bulut-Karslioglu), Dept. of Genome Regulation (Head: Alexander Meissner), Max Planck Institute for Molecular Genetics, Max Planck Society;

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Buschow,  René       
Microscopy and Cryo Electron Microscopy (Thorsten Mielke), Scientific Service, Max Planck Institute for Molecular Genetics, Max Planck Society;

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Riemenschneider,  Christina       
Dept. of Genome Regulation (Head: Alexander Meissner), Max Planck Institute for Molecular Genetics, Max Planck Society;

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Walther,  Maria       
Dept. of Genome Regulation (Head: Alexander Meissner), Max Planck Institute for Molecular Genetics, Max Planck Society;

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Meissner,  Alexander       
Dept. of Genome Regulation (Head: Alexander Meissner), Max Planck Institute for Molecular Genetics, Max Planck Society;

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引用

Bolondi, A., Law, B. K., Kretzmer, H., Gassaloglu, S. I., Buschow, R., Riemenschneider, C., Yang, D., Walther, M., Veenvliet, Jesse V., Meissner, A., Smith, Z. D., & Chan, M. M. (2024). Reconstructing axial progenitor field dynamics in mouse stem cell-derived embryoids. Developmental Cell, 59(12), 1489-1505. doi:10.1016/j.devcel.2024.03.024.


引用: https://hdl.handle.net/21.11116/0000-000F-5F0B-C
要旨
Embryogenesis requires substantial coordination to translate genetic programs to the collective behavior of differentiating cells, but understanding how cellular decisions control tissue morphology remains conceptually and technically challenging. Here, we combine continuous Cas9-based molecular recording with a mouse embryonic stem cell-based model of the embryonic trunk to build single-cell phylogenies that describe the behavior of transient, multipotent neuro-mesodermal progenitors (NMPs) as they commit into neural and somitic cell types. We find that NMPs show subtle transcriptional signatures related to their recent differentiation and contribute to downstream lineages through a surprisingly broad distribution of individual fate outcomes. Although decision-making can be heavily influenced by environmental cues to induce morphological phenotypes, axial progenitors intrinsically mature over developmental time to favor the neural lineage. Using these data, we present an experimental and analytical framework for exploring the non-homeostatic dynamics of transient progenitor populations as they shape complex tissues during critical developmental windows.