A human embryonic limb cell atlas resolved in space and time DOI Creative Commons
Bao Zhang, Peng He, John E. Lawrence

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2022, Volume and Issue: unknown

Published: April 28, 2022

Abstract Human limbs emerge during the fourth post-conception week as mesenchymal buds which develop into fully-formed over subsequent months. Limb development is orchestrated by numerous temporally and spatially restricted gene expression programmes, making congenital alterations in phenotype common. Decades of work with model organisms has outlined fundamental processes underlying vertebrate limb development, but an in-depth characterisation this process humans yet to be performed. Here we detail human embryonic across space time, using both single-cell spatial transcriptomics. We demonstrate extensive diversification cells, progressing from a number multipotent progenitors myriad mature cell states, identify several novel populations, including neural fibroblasts multiple distinct states. uncover two waves muscle each characterised different states regulated separate programmes. musculin (MSC) key transcriptional repressor maintaining stem identity validate performing MSC knock down myoblasts, results significant upregulation late myogenic genes. Through integration anatomically continuous transcriptomic samples, map clusters sagittal section whole fetal hindlimb. reveal clear anatomical segregation between genes linked brachydactyly polysyndactyly, transcriptionally populations mesenchyme autopod. Finally, perform scRNA-seq on murine facilitate cross-species developmental comparison at resolution, finding substantial homology species.

Language: Английский

A human embryonic limb cell atlas resolved in space and time DOI Creative Commons
Bao Zhang, Peng He, John E. Lawrence

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2022, Volume and Issue: unknown

Published: April 28, 2022

Abstract Human limbs emerge during the fourth post-conception week as mesenchymal buds which develop into fully-formed over subsequent months. Limb development is orchestrated by numerous temporally and spatially restricted gene expression programmes, making congenital alterations in phenotype common. Decades of work with model organisms has outlined fundamental processes underlying vertebrate limb development, but an in-depth characterisation this process humans yet to be performed. Here we detail human embryonic across space time, using both single-cell spatial transcriptomics. We demonstrate extensive diversification cells, progressing from a number multipotent progenitors myriad mature cell states, identify several novel populations, including neural fibroblasts multiple distinct states. uncover two waves muscle each characterised different states regulated separate programmes. musculin (MSC) key transcriptional repressor maintaining stem identity validate performing MSC knock down myoblasts, results significant upregulation late myogenic genes. Through integration anatomically continuous transcriptomic samples, map clusters sagittal section whole fetal hindlimb. reveal clear anatomical segregation between genes linked brachydactyly polysyndactyly, transcriptionally populations mesenchyme autopod. Finally, perform scRNA-seq on murine facilitate cross-species developmental comparison at resolution, finding substantial homology species.

Language: Английский

Citations

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