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Modeling human limb skeletal development using human pluripotent stem cell-derived skeletal assembloids [bulkRNA-seq]

ABSTRACT: Modeling human limb skeletal development using human pluripotent stem cell-derived skeletal assembloids [bulkRNA-seq]

PROVIDER: PRJNA1215760 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR32128129_1.fastq.gz	Fastqsanger.gz
	SRR32128129_2.fastq.gz	Fastqsanger.gz
	SRR32128130_1.fastq.gz	Fastqsanger.gz
	SRR32128130_2.fastq.gz	Fastqsanger.gz
	SRR32128131_1.fastq.gz	Fastqsanger.gz

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Modeling human limb skeletal development using human pluripotent stem cell-derived skeletal assembloids [bulkRNA-seq]

Project description:Despite recent advances in pluripotent stem cell-based approaches to induce skeletal cells, recapitulating human limb skeletal development in terms of structure and longitudinally oriented growth remains an unresolved challenge. Here, we report a method to differentiate human pluripotent stem cells into region-specific skeletal organoids harboring GDF5+PRG4+ interzone/articular chondrocyte　progenitors (IZ/ACPs) and SP7+ growth plate chondrocytes (GPCs) via PRRX1⁺ limb-bud mesenchymal cells. Comparative analysis demonstrated marked similarities of IZ/ACP and GPC organoids to the human embryonic limb, and graft fate and regenerative capacity in vivo were further characterized. We also mimicked the limb skeletal developmental process in a spatially structured manner by vertically positioning two IZ/ACP organoids at both ends of a GPC organoid to generate a human skeletal assembloid. Notably, this human skeletal assembloid recapitulated endochondral ossification with longitudinal skeletal growth upon transplantation. In summary, our study provides a novel research platform for human limb skeletal development and disease.

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