Protein kinase A accelerates the rate of early stage differentiation of pluripotent stem cells

• Published in: Biochemical and biophysical research communications Vol. 524; no. 1; pp. 57 - 63
• Main Authors: Minakawa, Tomohiro, Kanki, Yasuharu, Nakamura, Kae, Yamashita, Jun K.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 26-03-2020
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2019.12.098

In normal development, the rate of cell differentiation is tightly controlled and critical for normal development and stem cell differentiation. However, the underlying mechanisms regulating the rate of the differentiation are unknown, and manipulation of the rate of the stem cell differentiation is currently difficult. Here we show that activation of protein kinase A (PKA) accelerates the rate of mouse embryonic stem cell (ESC) differentiation through an early loss of ESC pluripotency markers and early appearance of mesodermal and other germ layer cells. The activation of PKA hastened differentiation by increasing the expression of a histone H3 lysine 9 (H3K9) dimethyltransferase, G9a protein, and the level of a negative epigenetic histone mark, H3K9 dimethylation (H3K9me2), in the promoter regions of the pluripotency markers Nanog and Oct4. These results elucidate a novel role of PKA on ESC differentiation and offer an experimental model for controlling the rate of ESC differentiation.
•PKA activation in ESC differentiation accelerated the appearance of the three germ layers, especially mesoderm cells.•PKA activation reciprocally induced the earlier disappearance of pluripotency genes (Oct4, Nanog, Sox2).•PKA activation induced the expression of the H3K9 dimethyltransferase G9a.•PKA activation increased the level of H3K9 dimethylation on the promoter region of the pluripotency genes Nanog and Oct4.