Characterization of LSD1 Expression Within the Murine Eye

Abstract

The purpose of this study was to extend the current understanding of endogenous lysine-specific demethylase 1 (LSD1) expression spatially and temporally in the retina. Toward that end, we determined the localization and levels of LSD1 and its substrates H3K4me1 and H3K4me2 (H3K4me1/2) within the murine eye. METHODS. Immunofluorescent microscopy for LSD1, H3K4me1, and H3K4me2 was conducted on murine formalin-fixed paraffin-embedded eye sections across development in addition to Western immunoblotting to assess localization and protein levels. RESULTS. Retinal LSD1 protein levels were highest at postnatal day 7 (P7), whereas its substrates H3K4me1 and H3K4me2 had equally high levels at P2 and P14. Concentrations of all three proteins gradually decreased over developmental time until reaching a basement level of~60% of maximum at P36. LSD1 and H3K4me1/2 were expressed uniformly in all retinal progenitor cells. By P36, there was variability in LSD1 expression in the ganglion cell layer, uniform expression in the inner nuclear layer, and dichotomous expression between photoreceptors in the outer nuclear layer. This contrasted with H3K4me1/2 expression, which remained uniform. Additionally, LSD1 was widely expressed in the lens, cornea, and retinal pigment epithelium. CONCLUSIONS. Consistent with its known role in neuronal differentiation, LSD1 is highly and uniformly expressed throughout all retinal progenitor cells. Variability in LSD1 expression, particularly in photoreceptors, may be indicative of their unique transcriptomes and epigenetic patterns of rods and cones. Murine rod nuclei exhibit LSD1 expression in a ring or shell, rather than throughout the nucleus, consistent with their unique inverted chromatin organization. LSD1 has substantial expression throughout adulthood, especially in cone nuclei. By providing insight into endogenous LSD1 expression, our current findings could directly inform future studies to determine the exact role of Lsd1 in the development and maintenance of specific structures and cell types within the eye.

Electrophysiologic and Morphologic Strain Differences in a Low-Dose NaIO3-Induced Retinal Pigment Epithelium Damage Model

“…#Fisher BP2401-500) at −80 °C for 4 days, embedded in paraffin, and sectioned through the sagittal plane on a microtome at thickness of 5 µm, with minor variation of the freeze-substitution method of Mary-Sinclair et al 28 Sections were used for hematoxylin and eosin staining, as described previously. 29 All sections were imaged with a bright-field microscope with a 20× objective.…”

Histone lysine-specific demethylase 1 regulates the proliferation of hemocytes in the oyster Crassostrea gigas

“…The distribution of LSD1 matched the cell- and stage-specific patterns of H3K4 methylation during male germ cell differentiation ( 57 ). Furthermore, initiation of LSD1 expression induced the differentiation of some retinal progenitor cells (RPCs), suggesting that LSD1 was highly and uniformly expressed in the eye of mouse and played a critical role in the differentiation of RPCs ( 58 ). In this study, the mRNA transcripts of Cg LSD1 were widely detected in all the tested tissues with the highest expression level in the mantle and a relatively higher expression level in hemocytes.…”

MiR-655-3p inhibits the progression of osteoporosis by targeting LSD1 and activating BMP-2/Smad signaling pathway

“…LSD1 knockdown could inhibit cancer or disease development, and thus it is an attractive target for providing novel therapeutics. [37][38][39] It has been reported that LSD1 served as a negative regulator of osteogenesis. 28 Likewise, in our study, we discovered that the mRNA and protein expression of LSD1 were obviously upregulated both in OVX mice and under MG. LSD1 deficiency facilitated osteogenic differentiation while suppressed apoptosis in MC3T3-E1 cells under simulated MG.…”