Dataset Information

A Transcriptomics Analysis of the Regulation of Fiber Cell Differentiation in the Absence of FGFRs and PTEN

ABSTRACT: The addition of 50% vitreous humor to the media bathing lens epithelial explants results in the induction of both lens fiber cell differentiation and a significant immune/inflammatory response. Although Fgfr loss blocks differentiation in lens epithelial explants, this loss can be partially rescued by deleting Pten, demonstrating an epistatic relationship between FGFR-signaling and PTEN. To investigate the functions of Fgfrs and Pten during lens fiber cell differentiation, we utilized a lens epithelial explant system and conducted RNA sequencing on vitreous humor-exposed explants lacking Fgfrs, or Pten or both Fgfrs and Pten. We found that Fgfr loss impairs both vitreous-induced differentiation and inflammation while the additional loss of Pten restores these responses. Additionally, vitreous exposure triggers a less pronounced immune response in explants lacking both Fgfrs and Pten than in wildtype explants, but a stronger immune response than in explants lacking only Fgfrs. Furthermore, transcriptomic analysis suggested that PDGFR-signaling in FGFR-deficient explants might be required to mediate the rescue of vitreous-induced fiber cell differentiation in explants lacking both Fgfrs and Pten. The blockage of β- crystallin induction in explants lacking both Fgfrs and Pten in the presence of a PDGFR-inhibitor supports this hypothesis. Our findings demonstrate that a wide array of genes associated with fiber cell differentiation are downstream of FGFR-signaling and that the vitreous-induced immune responses also depend on FGFR-signaling. Our data also demonstrates that many of the vitreous-induced gene expression changes Fgfr-deficient explants can be rescued in explants lacking both Fgfrs and Pten.

ORGANISM(S): Mus musculus

PROVIDER: GSE264405 | GEO | 2024/08/02

REPOSITORIES: GEO

ACCESS DATA

Similar Datasets

Project description:The mature eye lens contains a surface layer of epithelial cells called the lens epithelium that require a functional mitochondrial population to maintain the homeostasis and transparency of the entire lens. The lens epithelium overlies a core of terminally differentiated fiber cells that must degrade their mitochondria to achieve lens transparency. These distinct mitochondrial populations make the lens a useful model system to identify those genes that regulate the balance between mitochondrial homeostasis and elimination. Here we used an RNA sequencing and bioinformatics approach to identify the transcript levels of all genes expressed by distinct regions of the lens epithelium and maturing fiber cells of the embryonic Gallus gallus (chicken) lens. Our analysis detected over 15,000 unique transcripts expressed by the embryonic chicken lens. Of these, over 3000 transcripts exhibited significant differences in expression between lens epithelial cells and fiber cells. Multiple transcripts coding for separate mitochondrial homeostatic and degradation mechanisms were identified to exhibit preferred patterns of expression in lens epithelial cells that require mitochondria relative to lens fiber cells that require mitochondrial elimination. These included differences in the expression levels of metabolic, autophagy, and mitophagy transcripts between lens epithelial cells and lens fiber cells. These data provide a comprehensive window into all genes transcribed by the lens and those mitochondrial regulatory and degradation pathways that function to maintain mitochondrial populations in the lens epithelium and to eliminate mitochondria in maturing lens fiber cells. Differentiation-state transcriptional analysis of embryonic chicken lenses was performed following microdissection of 100 embryonic day 13 (E13) chicken lenses into four distinct regions that represent a continuum of lens cell differentiation states: lens central epithelium (EC), equatorial epithelium (EQ), cortical fibers (FP), and central fibers (FC). Further analysis of the transcriptional content of biologically replicate samples was performed by Illumina directional mRNA sequencing and resulting reads mapped by TopHat and assembled with Cufflinks.

Dataset Information

A Transcriptomics Analysis of the Regulation of Fiber Cell Differentiation in the Absence of FGFRs and PTEN

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure