GEO series

Dynamic transcriptional and epigenetic changes define postnatal tendon growth

GSE272888 Mus musculus Expression profiling by high throughput sequencing; Genome binding/occupancy profiling by high throughput sequencing 54 samples Submitted 2025/10/12 Platform GPL19057

Summary

Tendons are dynamic structures that efficiently transmit forces and enable movement. From birth, tendons undergo dramatic changes from a principally cellular tissue to a hypocellular one characterized by a dense and highly ordered extracellular matrix. During this time, tendon cells change morphology from rounded to stellate in appearance and their proliferative rates decline. There is also significant expansion and maturation of the extracellular matrix (ECM) as tendons grow in length and diameter and alter their biomechanical properties to sustain increased physical activities. Surprisingly, for such an important stage of tendon maturation, we understand very little about the transcriptional and epigenetic regulators that direct these processes. Here, we present a roadmap of genes that are differentially regulated during the early neonatal and postnatal time period. We find differentially expressed genes fall into specific transcriptional modules, representing expression increases, decreases, or gene sets undergoing dynamic changes over postnatal time. By pairing our transcriptomic data with epigenetic data, we were able to perform an integrative analysis of the datasets and further define modules with highly correlated changes in gene expression and chromatin accessibility. From this analysis, several new pathways emerge. Among them, we focus on Yap1, a transcriptional co-activator of the Hippo signaling pathway. We observe accessible regions near to differentially expressed genes, containing motifs for TEAD, the transcription factor that binds Yap to regulate transcription. Conditional loss of Yap1 at postnatal stages results in altered expression of Col1a1 and disrupted matrix organization and density, suggesting that Yap is important for refining tendon ECM maturation. Together, our analyses identify a regulator of matrix maturation and provides a rich dataset with which to interrogate transcriptional networks and pathways during this poorly understood time in tendon growth.

Published in

Dingwall HL, Grinstein M, Peterson B et al. · PLoS genetics 2025 · PMID 41252420 · doi:10.1371/journal.pgen.1011902

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Direct links to NCBI, no account and no request form: the whole study as GSE272888_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 54 samples. Raw sequencing reads are also available from ENA.

Whole study · RAW.tar ↓ Series matrix ↓ All supplementary files ↗ Raw reads on ENA ↗

Also filed as BioProject PRJNA1139180 and SRA study SRP521691. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41252420) ↗

Study design

40 conditions, each sampled once — no replicated groups

Read from the first 40 of 54 sample titles: 40 distinct titles with little repetition. Check it against the sample list below before relying on it.

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