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Genome-wide strategies identify downstream target genes of connective tissue-associated transcription factors

ABSTRACT: Genome-wide strategies identify downstream target genes of connective tissue-associated transcription factors

PROVIDER: PRJNA391992 | ENA |

REPOSITORIES: ENA

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

Project description:Connective tissues support organs and play crucial roles in development, homeostasis and fibrosis, yet our understanding of their formation is still limited. To gain insight into the molecular mechanisms of connective tissue specification, we selected five zinc finger transcription factors - OSR1, OSR2, EGR1, KLF2 and KLF4 - based on their expression patterns and/or known involvement in connective tissue subtype differentiation. RNA-seq and ChIP-seq profiling revealed a set of common genes regulated by all five transcription factors, which we propose as connective tissue core expression set. This common core was enriched in genes associated with axon guidance and myofibroblast signature, including fibrosis-related genes. In addition, each transcription factor regulated a specific set of signalling molecules and extracellular matrix components. This suggests a concept whereby local molecular niches can be created via the expression of specific transcription factors impinging on the specification of local microenvironments. The regulatory network established here identifies common and distinct molecular signatures of limb connective tissue subtypes, provides novel insight into the signalling pathways governing connective tissue specification, and serves as a resource for connective tissue development.

2017-07-19 | GSE100516 | GEO

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

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

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Genome-wide strategies identify downstream target genes of connective tissue-associated transcription factors

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Genome-wide strategies reveal downstream target genes of Npas4l associated with cardiovascular development in zebrafish

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

Project description: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.

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