Kondrogenezde Gen İfade Kalıpları ve Fenotipik İlişkiler: İskelet Displazisi Nozolojisine Dair Yaklaşımlar

Öz

Kondrogenez olarak bilinen mezenkimal kök hücrelerin (MKH) kondrositlere farklılaşması, kıkırdak oluşumu ve iskelet gelişiminde temel rol oynayan karmaşık bir süreçtir. Bu çalışma, RNA-seq verilerini kullanarak kondrojenezin çeşitli aşamalarındaki (erken, orta ve geç) transkripsiyonel dinamikleri ve fenotipik korelasyonları aydınlatmaktadır. Çalışmada, Transkripsiyon faktörlerinin (TF'ler) ve RNA-bağlayıcı proteinlerin (RBP'ler) diferansiyel ekspresyonuna odaklandık. En yüksek ifade dönemlerinde kritik genleri belirledik ve bu zamansal kalıpları görselleştirmek için ısı haritaları oluşturduk. Ayrıca, DisGeNET veri tabanını kullanarak iskelet displazisi nozoloji genlerinin kapsamlı bir analizini yaptık, en yüksek ekspresyon dönemlerini ve fenotipik etkilerini belirledik. Bulgularımız, erken evre (D1) gen ifadesinin kraniyofasiyal gelişim ve uzuv oluşumu anomalileri ile bağlantılı olduğunu, öncelikle ECM organizasyonu ve sinyal iletiminden sorumlu genleri içerdiğini ortaya koymaktadır. Orta evre (D7) genleri, kondrosit proliferasyonu ve matris birikimindeki rolleri vurgulayarak kıkırdak matris bileşimi ve iskelet büyümesi ile ilişkilidir. Geç evre (D21) genleri kemik mineral yoğunluğu, kıkırdak bütünlüğü ve eklem oluşumunda rol oynayarak kıkırdak dokusunun olgunlaşmasını ve işlevselliğini sağlar. Bu çalışma, kondrogenez sırasında gen ekspresyon düzenleyicilerinin ve fenotipik korelasyonlarının ayrıntılı bir analizini sunarak, kıkırdak gelişimi ve iskelet displazilerini yönlendiren moleküler mekanizmalar hakkında fikir vermektedir. Bu zamansal gen ifadesi modellerinin anlaşılması, kondrojenez hakkındaki bilgilerimizi artırmakta ve kıkırdakla ilgili hastalıklar için hedefe yönelik tedavilerin geliştirilmesine yardımcı olmaktadır. Bu bulgular, farklılaşma süreci boyunca gen ifadesinin dinamik düzenlemesini yakalamada zaman noktası analizlerinin öneminin altını çizmektedir.

Anahtar Kelimeler

• kondrogenez
• iskelet displazisi
• transkriptomik

Gene Expression Patterns and Phenotypic Associations in Chondrogenesis: Insights into Skeletal Dysplasia Nosology

Öz

The differentiation of mesenchymal stem cells (MSCs) into chondrocytes, known as chondrogenesis, is a complex process that plays a fundamental role in cartilage formation and skeletal development. This study elucidates the transcriptional dynamics and phenotypic correlations at various stages of chondrogenesis (early, mid, and late) using RNA-seq data. We focused on the differential expression of transcription factors (TFs) and RNA-binding proteins (RBPs). We identified critical genes during their highest expression periods and generated heatmaps to visualize these temporal patterns. Additionally, we conducted a comprehensive analysis of skeletal dysplasia nosology genes, determining their highest expression periods and phenotypic implications using the DisGeNET database. Our findings reveal that early-stage (D1) gene expression is linked to craniofacial development and limb formation anomalies, primarily involving genes responsible for extracellular matrix (ECM) organization and signal transduction. Mid-stage (D7) genes are associated with cartilage matrix composition and skeletal growth, highlighting roles in chondrocyte proliferation and matrix deposition. Late-stage (D21) genes are implicated in bone mineral density, cartilage integrity, and joint formation, ensuring the maturation and functionality of cartilage tissue. This study provides a detailed analysis of gene expression regulators and their phenotypic correlations during chondrogenesis, offering insights into the molecular mechanisms driving cartilage development and skeletal dysplasias. Understanding these temporal gene expression patterns enhances our knowledge of chondrogenesis and aids in developing targeted therapies for cartilage-related diseases. These findings underscore the significance of time-point analyses in capturing the dynamic regulation of gene expression throughout the differentiation process.

Anahtar Kelimeler

• transcriptomics
• skeletal dysplasias
• chondrogenesis

Kaynakça

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