Protein arginine methyltransferase 1 regulates cell proliferation and differentiation in adult mouse adult intestine

Cell & Bioscience

Bingyin Shi¹  Lingyu Bao²  Lu Xue³  Yijun Su⁴  Yun-Bo Shi⁵  Julia Roediger⁵ 

[1] Department of Endocrinology, The First Affiliated Hospital of Xi’an Jiaotong University School of Medicine, No. 277, Yanta West Road, 710061, Xi’an, Shaanxi, People’s Republic of China;Department of Endocrinology, The First Affiliated Hospital of Xi’an Jiaotong University School of Medicine, No. 277, Yanta West Road, 710061, Xi’an, Shaanxi, People’s Republic of China;Section on Molecular Morphogenesis, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), 20892, Bethesda, MD, USA;Institute for Medical Biology and Hubei Provincial Key Laboratory for Protection and Application of Special Plants in Wuling Area of China, College of Life Sciences, South-Central University for Nationalities, 182 Minyuan Road, Hongshan District, 430074, Wuhan, China;Section on Molecular Morphogenesis, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), 20892, Bethesda, MD, USA;Laboratory of High Resolution Optical Imaging and Advanced Imaging and Microscopy Resource, National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH), 20892, Bethesda, MD, USA;Section on Molecular Morphogenesis, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), 20892, Bethesda, MD, USA;

关键词: Adult organ-specific stem cell;    Histone arginine methyltransferase;    Intestine;    Transcription coactivator;    Thyroid hormone receptor;   

DOI  :  10.1186/s13578-021-00627-z

来源: Springer

【 摘 要 】

BackgroundAdult stem cells play an essential role in adult organ physiology and tissue repair and regeneration. While much has been learnt about the property and function of various adult stem cells, the mechanisms of their development remain poorly understood in mammals. Earlier studies suggest that the formation of adult mouse intestinal stem cells takes place during the first few weeks after birth, the postembryonic period when plasma thyroid hormone (T3) levels are high. Furthermore, deficiency in T3 signaling leads to defects in adult mouse intestine, including reduced cell proliferation in the intestinal crypts, where stem cells reside. Our earlier studies have shown that protein arginine methyltransferase 1 (PRMT1), a T3 receptor coactivator, is highly expressed during intestinal maturation in mouse.MethodsWe have analyzed the expression of PRMT1 by immunohistochemistry and studied the effect of tissue-specific knockout of PRMT1 in the intestinal epithelium.ResultsWe show that PRMT1 is expressed highly in the proliferating transit amplifying cells and crypt base stem cells. By using a conditional knockout mouse line, we have demonstrated that the expression of PRMT1 in the intestinal epithelium is critical for the development of the adult mouse intestine. Specific removal of PRMT1 in the intestinal epithelium results in, surprisingly, more elongated adult intestinal crypts with increased cell proliferation. In addition, epithelial cell migration along the crypt-villus axis and cell death on the villus are also increased. Furthermore, there are increased Goblet cells and reduced Paneth cells in the crypt while the number of crypt base stem cells remains unchanged.ConclusionsOur finding that PRMT1 knockout increases cell proliferation is surprising considering the role of PRMT1 in T3-signaling and the importance of T3 for intestinal development, and suggests that PRMT1 likely regulates pathways in addition to T3-signaling to affect intestinal development and/or homeostasis, thus affecting cell proliferating and epithelial turn over in the adult.

【 授权许可】

CC BY