Otic Neurogenesis Is Regulated by TGFβ in a Senescence-Independent Manner

Magariños, Marta; Barajas-Azpeleta, Raquel; Varela-Nieto, Isabel; Aburto, María Rodríguez

doi:10.3389/fncel.2020.00217

Cited by 3 publications

(2 citation statements)

References 40 publications

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“…The pattern of cell death in the developing avian heart also strongly correlates with SA-β-GAL staining ( Lorda-Díez et al, 2019 ), as do areas of cell death in the somites, tail bud, and CNS ( Muñoz-Espín et al, 2013 ; Storer et al, 2013 ). In the case of the developing otic vesicle in the chicken, SA-β-GAL labeled cells are associated with areas of increased apoptosis ( Figures 1A–C ) ( Gibaja et al, 2019 ; Magariños et al, 2020 ). In mice, it has been found that senescence in the endolymphatic sac has a morphogenetic role analogous to that of apoptosis ( Muñoz-Espín et al, 2013 ).…”

Section: Sa-β-gal Staining In the Developing Embryomentioning

confidence: 99%

Is Senescence-Associated β-Galactosidase a Reliable in vivo Marker of Cellular Senescence During Embryonic Development?

Mera-Rodríguez

Álvarez-Hernán

Gañán

et al. 2021

Front. Cell Dev. Biol.

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During vertebrate embryonic development, cellular senescence occurs at multiple locations. To date, it has been accepted that when there has been induction of senescence in an embryonic tissue, β-galactosidase activity is detectable at a pH as high as 6.0, and this has been extensively used as a marker of cellular senescence in vivo in both whole-mount and cryosections. Such senescence-associated β-galactosidase (SA-β-GAL) labeling appears enhanced in degenerating regions of the vertebrate embryo that are also affected by programmed cell death. In this sense, there is a strong SA-β-GAL signal which overlaps with the pattern of cell death in the interdigital tissue of the developing limbs, and indeed, many of the labeled cells detected go on to subsequently undergo apoptosis. However, it has been reported that β-GAL activity at pH 6.0 is also enhanced in healthy neurons, and some retinal neurons are strongly labeled with this histochemical technique when they begin to differentiate during early embryonic development. These labeled early post-mitotic neurons also express other senescence markers such as p21. Therefore, the reliability of this histochemical technique in studying senescence in cells such as neurons that undergo prolonged and irreversible cell-cycle arrest is questionable because it is also expressed in healthy post-mitotic cells. The identification of new biomarkers of cellular senescence would, in combination with established markers, increase the specificity and efficiency of detecting cellular senescence in embryonic and healthy mature tissues.

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Section: Sa-β-gal Staining In the Developing Embryomentioning

confidence: 99%

Is Senescence-Associated β-Galactosidase a Reliable in vivo Marker of Cellular Senescence During Embryonic Development?

Mera-Rodríguez

Álvarez-Hernán

Gañán

et al. 2021

Front. Cell Dev. Biol.

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“…We identified several mRNAs regulated by miR-21 that are likely to contribute to the regeneration of embryonic and adult tissues (including the endometrium) by promoting cell cycle quiescence, cell differentiation, migration, and/or angiogenesis [38][39][40][41][42]. Some have been also implicated in the reversal of cellular senescence [43][44][45], the attenuation of fibrosis [45,46] and the stress response [47,48]. Specifically, BDKRB1, a bradykinin G-coupled receptor B1, was significantly upregulated in eSFs by miR-21.…”

Section: Discussionmentioning

confidence: 99%

Bone marrow mesenchymal stem cell-derived exosomes shuttle microRNAs to endometrial stromal fibroblasts that promote tissue proliferation /regeneration/ and inhibit differentiation

Bonavina,

Mamillapalli,

Krikun

et al. 2024

Stem Cell Res Ther

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Background Human bone marrow-derived stem cells (hBMDSCs) are well characterized mediators of tissue repair and regeneration. An increasing body of evidence indicates that these cells exert their therapeutic effects largely through their paracrine actions rather than clonal expansion and differentiation. Here we studied the role of microRNAs (miRNAs) present in extracellular vesicles (EVs) from hBMDSCs in tissue regeneration and cell differentiation targeting endometrial stromal fibroblasts (eSF). Methods Extracellular vesicles (EVs) are isolated from hBMDSCs, characterized by transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA) techniques. Extracted total RNA from EVs was subjected to RNA seq analysis. Transfection and decidualization studies were carried out in endometrial stromal fibroblasts (eSF). Gene expression was analyzed by qRTPCR. Unpaired t-test with Welch’s correction was used for data analysis between two groups. Results We identified several microRNAs (miRNAs) that were highly expressed, including miR-21-5p, miR-100-5p, miR-143-3p and let7. MiR-21 is associated with several signaling pathways involved in tissue regeneration, quiescence, cellular senescence, and fibrosis. Both miR-100-5p and miR-143-3p promoted cell proliferation. MiR-100-5p specifically promoted regenerative processes by upregulating TGF-ß3, VEGFA, MMP7, and HGF. MiR-100-5p blocked differentiation or decidualization as evidenced by morphologic changes and downregulation of decidualization mediators including HOXA10, IGFBP1, PRL, PR-B, and PR. Conclusion EVs delivered to tissues by hBMDSCs contain specific miRNAs that prevent terminal differentiation and drive repair and regeneration. Delivery of microRNAs is a novel treatment paradigm with the potential to replace BMDSCs in cell-free regenerative therapies.

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Analysis of Programmed Cell Death and Senescence Markers in the Developing Retina of an Altricial Bird Species

Álvarez-Hernán

Mera-Rodríguez

Hernández-Núñez

et al. 2021

Cells

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This study shows the distribution patterns of apoptotic cells and biomarkers of cellular senescence during the ontogeny of the retina in the zebra finch (T. guttata). Neurogenesis in this altricial bird species is intense in the retina at perinatal and post-hatching stages, as opposed to precocial bird species in which retinogenesis occurs entirely during the embryonic period. Various phases of programmed cell death (PCD) were distinguishable in the T. guttata visual system. These included areas of PCD in the central region of the neuroretina at the stages of optic cup morphogenesis, and in the sub-optic necrotic centers (St15–20). A small focus of early neural PCD was detected in the neuroblastic layer, dorsal to the optic nerve head, coinciding with the appearance of the first differentiated neuroblasts (St24–St25). There were sparse pyknotic bodies in the non-laminated retina between St26 and St37. An intense wave of neurotrophic PCD was detected in the laminated retina between St42 and P8, the last post-hatching stage included in the present study. PCD was absent from the photoreceptor layer. Phagocytic activity was also detected in Müller cells during the wave of neurotrophic PCD. With regard to the chronotopographical staining patterns of senescence biomarkers, there was strong parallelism between the SA-β-GAL signal and p21 immunoreactivity in both the undifferentiated and the laminated retina, coinciding in the cell body of differentiated neurons. In contrast, no correlation was found between SA-β-GAL activity and the distribution of TUNEL-positive cells in the developing tissue.

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Otic Neurogenesis Is Regulated by TGFβ in a Senescence-Independent Manner

Cited by 3 publications

References 40 publications

Is Senescence-Associated β-Galactosidase a Reliable in vivo Marker of Cellular Senescence During Embryonic Development?

Is Senescence-Associated β-Galactosidase a Reliable in vivo Marker of Cellular Senescence During Embryonic Development?

Bone marrow mesenchymal stem cell-derived exosomes shuttle microRNAs to endometrial stromal fibroblasts that promote tissue proliferation /regeneration/ and inhibit differentiation

Analysis of Programmed Cell Death and Senescence Markers in the Developing Retina of an Altricial Bird Species

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