Mesenchymal stem cells (MSCs) are characterized by their self-renewing capacity and differentiation potential into multiple tissues. Thus, management of the differentiation capacities of MSCs is important for MSC-ba...Mesenchymal stem cells (MSCs) are characterized by their self-renewing capacity and differentiation potential into multiple tissues. Thus, management of the differentiation capacities of MSCs is important for MSC-based regenerative medicine, such as craniofacial bone regeneration, and in new treatments for metabolic bone diseases, such as osteoporosis. In recent years, histone modification has been a growing topic in the field of MSC lineage specification, in which the Su(var)3-9, enhancer-of-zeste, trithorax (SET) domain-containing family and the Jumonji C (JmjC) domain-containing family represent the major histone lysine methyltransferases (KMTs) and histone lysine demethylases (KDMs), respectively. In this review, we summarize the current understanding of the epigenetic mechanisms by which SET domain-containine KMTs and JmiC domain-containinlz KDMs balance the osteogenic and adipogenic differentiation of MSCs.展开更多
Lysine specific demethylase 1(LSD1),a transcriptional corepressor or coactivator that serves as a demethylase of histone 3 lysine 4 and 9,has become a potential therapeutic target for cancer therapy.LSD1 mediates many...Lysine specific demethylase 1(LSD1),a transcriptional corepressor or coactivator that serves as a demethylase of histone 3 lysine 4 and 9,has become a potential therapeutic target for cancer therapy.LSD1 mediates many cellular signaling pathways and regulates cancer cell proliferation,invasion,migration,and differentiation.Recent research has focused on the exploration of its pharmacological inhibitors.Natural products are a major source of compounds with abundant scaffold diversity and structural complexity,which have made a major contribution to drug discovery,particularly anticancer agents.In this review,we briefly highlight recent advances in natural LSD1 inhibitors over the past decade.We present a comprehensive review on their discovery and identification process,natural plant sources,chemical structures,anticancer effects,and structure-activity relationships,and finally provide our perspective on the development of novel natural LSD1 inhibitors for cancer therapy.展开更多
基金supported by the National Institute of Dental and Craniofacial Research grants, K08DE024603-02, DE019412, and DE01651a grant from 111 Project of MOE, Chinasupported by Open Fund of State Key Laboratory of Oral Diseases, Sichuan University
文摘Mesenchymal stem cells (MSCs) are characterized by their self-renewing capacity and differentiation potential into multiple tissues. Thus, management of the differentiation capacities of MSCs is important for MSC-based regenerative medicine, such as craniofacial bone regeneration, and in new treatments for metabolic bone diseases, such as osteoporosis. In recent years, histone modification has been a growing topic in the field of MSC lineage specification, in which the Su(var)3-9, enhancer-of-zeste, trithorax (SET) domain-containing family and the Jumonji C (JmjC) domain-containing family represent the major histone lysine methyltransferases (KMTs) and histone lysine demethylases (KDMs), respectively. In this review, we summarize the current understanding of the epigenetic mechanisms by which SET domain-containine KMTs and JmiC domain-containinlz KDMs balance the osteogenic and adipogenic differentiation of MSCs.
基金This work was co-supported by National Natural Science Foundation of China(Nos.81803695 and 82104359)the Natural Science Fund in Jiangsu Province(BK20180568)+2 种基金the China Postdoctoral Science Foundation(2021M691647)the Fundamental Research Funds for the Central Universities(2632021ZD24)the Open Project of State Key Laboratory of Natural Medicines(SKLNMKF202207).
文摘Lysine specific demethylase 1(LSD1),a transcriptional corepressor or coactivator that serves as a demethylase of histone 3 lysine 4 and 9,has become a potential therapeutic target for cancer therapy.LSD1 mediates many cellular signaling pathways and regulates cancer cell proliferation,invasion,migration,and differentiation.Recent research has focused on the exploration of its pharmacological inhibitors.Natural products are a major source of compounds with abundant scaffold diversity and structural complexity,which have made a major contribution to drug discovery,particularly anticancer agents.In this review,we briefly highlight recent advances in natural LSD1 inhibitors over the past decade.We present a comprehensive review on their discovery and identification process,natural plant sources,chemical structures,anticancer effects,and structure-activity relationships,and finally provide our perspective on the development of novel natural LSD1 inhibitors for cancer therapy.