Ultrastructure of the sebaceous gland. (A) Column of differentiating sebocytes in Atg7f/f glands, with lipid droplets (LD) accumulating during differentiation (bottom to top) and dark secondary lysosomes (sLy). (B) Higher magnification of the condensed nucleus of the terminally differentiated cell (in A). The cytoplasm is filled with a darker mass, numerous small primary lysosomes, dark secondary lysosomes (sLy), and lipid droplets (LD). (C) Transitional SGl cells, with sebum (SB) in the upper half. Different stages of cell lysis are visible, with the cytoplasmic membrane being degraded (dashed line indicates a previous cell border) resulting in an open border to the cells below (open→). The lower cells are in a dissolving state, containing lipid droplets (LD) at various stages of fusion and disintegration. The cell at the bottom left contains a dilated, slightly hyperchromatic nucleus (N). (D) Higher magnification of the area (in C) displaying the onset of cell lysis, visible by the LD fusion and break up. In the lower left, the expanded trans-Golgi network of another cell is seen. (E) Column of terminal differentiating sebocytes in a hypertrophic atg7−/- gland. Cells are abundantly filled with LDs and several darkened secondary lysosomes (sLy). In cells bordering the sebum (SB) the nuclei are at different stages of condensation, one being pyknotic (F). The sebum has a more electron-dense and speckled appearance. (F) Higher magnification of the highly condensed and pyknotic nucleus of one of the sebocytes from the gland shown in E. The cytoplasm of this cell is filled with a perinuclear electron-dense material containing an expanded Golgi with numerous primary lysosomal vesicles. (G, H) Cells from a different SGl showing the formation of pathological residual bodies (RB), tertiary lysosomes, which occupies a large area of the cytoplasm. The inside of RB structure has a similar appearance as the sebum seen in the upper ductal part of the image shown in E. (H) At the border and in inner areas of the RB, rER, and ribosomes (→) accumulate, darkening the material. Many primary lysosomes are lined up at the border and are incorporated into the RB (►). Lipid droplets give the RB its speckled appearance. Abbreviations: Gg, Golgi apparatus; LD, lipid droplet; Ly, lysosomes; ►, lysosomes incorporated into the RB; N, nucleus; Nr, nuclear remnant; sLy, secondary lysosomes; RB, residual bodies; rER, rough ER; SB, sebum. Scale bars: 5 µm (A, C, and E), 1 µm (D, G, and H), 500 nm (B and F).