Modeling the differentiation of embryonic limb chondroprogenitors by cell death and cell senescence in high density micromass cultures and their regulation by FGF signaling
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Duarte Olivenza, Cristina; Hurlé González, Juan M.; Montero Simón, Juan Antonio; Lorda Diez, Carlos IgnacioFecha
2022Derechos
Attribution 4.0 International
© 2022 by the authors
Publicado en
Cells, 2022, 12(1), 175
Editorial
MDPI
Palabras clave
Apoptosis
Cell senescence
Chondrogenesis
Resumen/Abstract
Considering the importance of programmed cell death in the formation of the skeleton during embryonic development, the aim of the present study was to analyze whether regulated cell degeneration also accompanies the differentiation of embryonic limb skeletal progenitors in high-density tridimensional cultures (micromass cultures). Our results show that the formation of primary cartilage nodules in the micromass culture assay involves a patterned process of cell death and cell senescence, complementary to the pattern of chondrogenesis. As occurs in vivo, the degenerative events were preceded by DNA damage detectable by ?H2AX immunolabeling and proceeded via apoptosis and cell senescence. Combined treatments of the cultures with growth factors active during limb skeletogenesis, including FGF, BMP, and WNT revealed that FGF signaling modulates the response of progenitors to signaling pathways implicated in cell death. Transcriptional changes induced by FGF treatments suggested that this function is mediated by the positive regulation of the genetic machinery responsible for apoptosis and cell senescence together with hypomethylation of the Sox9 gene promoter. We propose that FGF signaling exerts a primordial function in the embryonic limb conferring chondroprogenitors with their biological properties.
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