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Limb connective tissue is organized in a continuum of promiscuous fibroblast identities during development

ABSTRACT: Although connective tissues play critical roles in development, our understanding of connective tissue fibroblast developmental programs lag behind that of other components of the musculoskeletal system mainly because fibroblasts are highly heterogeneous and poorly characterized. Combining single-cell RNA-sequencing-based strategies, including trajectory inference, and in situ hybridization analyses, we address the diversity of connective tissue fibroblasts and their developmental trajectories during chicken limb foetal development. We show that fibroblasts switch from a positional information to a lineage diversification program during their development. Muscle connective tissue and tendon contain several fibroblast populations that emerge asynchronously. In fine, these populations map to distinct layers, prefiguring the adult fibroblast layers. Populations that are close in transcriptional identity are found in neighboring layers. Altogether, we propose that the limb connective tissue is organised in a continuum of promiscuous fibroblasts identities, allowing for the robust and efficient connection of highly different tissues such as muscle, bone and skin.

ORGANISM(S): Gallus gallus

PROVIDER: GSE261503 | GEO | 2024/07/19

REPOSITORIES: GEO

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Unexpected contribution of fibroblasts to the muscle lineage during foetal myogenesis and role of BMP signalling in this process

Project description:Purpose : Positional information driving limb muscle patterning is considered to be contained in lateral plate mesoderm-derived tissues, such as tendon or muscle connective tissue and not in myogenic cells themselves. The current consensus is that myogenic cells originate from somites, while connective tissue fibroblasts originate from the lateral plate mesoderm. We challenged this model by cell and genetic lineage tracing experiments and identified that a subpopulation of limb myogenic cells did not originate from somite or Pax3 lineage, but rather originated from the lateral plate mesoderm and were derived from Osr1 and Scx lineages. Results: Analysis of single-cell RNA-sequencing data obtained from limb cells at successive developmental stages identified a subpopulation of cells displaying a dual muscle and connective tissue signature, in addition to independent muscle and connective tissue populations. Active BMP signalling was detected in this junctional cell sub-population and at the tendon/muscle interface in developing limbs. BMP gain- and loss-of-function experiments performed in vivo and in vitro showed that this signalling pathway regulated a fibroblast-to-myoblast conversion. Conclusions: We propose that localised BMP signalling converts a subset of lateral plate mesoderm-derived fibroblasts to a myogenic fate and establishes a boundary of fibroblast-derived myonuclei at the tendon/muscle interface to control the muscle pattern during limb development and myotendinous formation.

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Limb connective tissue is organized in a continuum of promiscuous fibroblast identities during development

Project description:Limb connective tissue is organized in a continuum of promiscuous fibroblast identities during development

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Induction of muscle-related gene expression in loose connective tissue fibroblasts in response to static tissue stretch

Project description:Current knowledge of mechanically-induced regulation of gene expression in fibroblast is mostly based on experiments using prolonged cyclical stretching of either cultured cells or load-bearing connective tissues such as tendons and ligaments. In this study, we have examined the effect of static tissue stretch on fibroblasts within loose connective tissue using in vivo and ex vivo models. In an in vivo trunk side bending model, one side of the trunk of the mouse was stretched while the other side was shortened under anesthesia for 90 minutes. In the ex vivo method, whole subcutaneous tissue explants (including skin, subcutaneous muscle and subcutaneous tissue) from both sides of the trunk were incubated ex vivo either stretched or not stretched (shortened) for 24 hours. Tissue stretch or shortening was followed by immediate dissection of the loose connective tissue layer on both sides of the trunk, RNA extraction and gene expression analysis using Affymetrix mouse gene arrays. In both in vivo and ex vivo experiments, a large cluster of genes related to skeletal muscle function and carbohydrate metabolism was up-regulated in the stretched, compared with the shortened, connective tissue samples. However, there were few differentially expressed matrix-related genes, and in particular no change in collagen genes. Immunohistochemical staining for myosin after tissue stretch for 24 hours ex vivo showed increased myosin immunoreactivity in fibroblasts within the stretched compared with the shortened tissue samples. These results suggest that dynamic modulation of muscle-related gene expression is a normal physiological response of loose connective tissue fibroblasts to changes in tissue length.. Keywords: response to mechanical stretch Within animal stretched vs shortened (randomized): 7 animals in vivo and 4 ex vivo.

2011-05-08 | E-GEOD-11371 | biostudies-arrayexpress

Induction of muscle-related gene expression in loose connective tissue fibroblasts in response to static tissue stretch

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Genome-wide strategies identify downstream target genes of connective tissue-associated transcription factors [ChIP-seq TFs]

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Transcriptome profile of Primary Human Lung Fibroblasts (Cystic Fibrosis vs. Non-Cystic Fibrosis) arranged in a 3D model of the connective airways tissue

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Persistent JunB Activation in Fibroblasts Disrupts Stem Cell Niche Interactions Enforcing Skin Aging [RNA-seq]

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