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Direct Reprogramming of Non-limb Fibroblasts to Cells with Properties of Limb Progenitors [bulkRNA-seq]

ABSTRACT: Direct Reprogramming of Non-limb Fibroblasts to Cells with Properties of Limb Progenitors [bulkRNA-seq]

PROVIDER: PRJNA704626 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR13777325_1.fastq.gz	Fastqsanger.gz
	SRR13777325_2.fastq.gz	Fastqsanger.gz
	SRR13777326_1.fastq.gz	Fastqsanger.gz
	SRR13777326_2.fastq.gz	Fastqsanger.gz
	SRR13777327_1.fastq.gz	Fastqsanger.gz

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Direct Reprogramming of Non-limb Fibroblasts to Cells with Properties of Limb Progenitors [bulkRNA-seq]

Project description:The early limb bud consists of mesenchymal progenitors (limb progenitors) derived from the lateral plate mesoderm (LPM) that produce most of the tissues of the mature limb bud. The LPM also gives rise to the mesodermal components of the trunk, flank and neck. However, the mesenchymal cells generated at these other axial levels cannot produce the variety of cell types found in the limb bud, nor can they be directed to form a patterned appendage-like structure, even when placed in the context of the signals responsible for organizing the limb bud. Here, by taking advantage of a direct reprogramming approach, we find a set of factors (Prdm16, Zbtb16, and Lin28) normally expressed in the early limb bud, that are capable of imparting limb progenitor-like properties to non-limb fibroblasts. Cells reprogrammed by these factors show similar gene expression profiles, and can differentiate into similar cell types, as endogenous limb progenitors. The further addition of Lin41 potentiates proliferation of the reprogrammed cells while suppressing differentiation. These results suggest that these same four key factors may play pivotal roles in the specification of endogenous limb progenitors.

2023-11-15 | GSE167419 | GEO

Direct Reprogramming of Non-limb Fibroblasts to Cells with Properties of Limb Progenitors

Project description:Direct Reprogramming of Non-limb Fibroblasts to Cells with Properties of Limb Progenitors

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Direct Reprogramming of Non-limb Fibroblasts to Cells with Properties of Limb Progenitors [scRNA-seq]

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Direct Reprogramming of Non-limb Fibroblasts to Cells with Properties of Limb Progenitors [scRNA-seq]

Project description:Direct Reprogramming of Non-limb Fibroblasts to Cells with Properties of Limb Progenitors [scRNA-seq]

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Blastemal progenitors modulate immune signaling during early limb regeneration.

Project description:Blastema formation is a hallmark of limb regeneration that requires proliferation and migration of progenitors derived from many tissues to the amputation plane. To better understand the genetic programs that initiate limb regeneration, we reasoned that blastemal progenitors would be among early proliferating cells in the stump following amputation. Here we separately profiled dividing and non-dividing stump tissues, as well as the wound epidermis, during early axolotl limb regeneration to examine transcriptional programs of blastemal progenitors. We provide a description of the changes in gene expression specific to early dividing cells at the site of amputation, inclusive of progenitors for the regenerating limb. This work collectively demonstrates differential suppression/activation of core developmental signaling pathways in subsets of the early regenerating limb and further suggests that interleukin-8 (il-8) signaling is important for regeneration.

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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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Identification of mesenchymal progenitors in the early limb bud

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