Long noncoding RNA ANCR inhibits the differentiation of mesenchymal stem cells toward definitive endoderm by facilitating the association of PTBP1 with ID2

• DOI: 10.1038/s41419-019-1738-3
• Publication Date: 2019-06-24T08:55:20Z
• Authors: Jing Li; Yanlei Yang; Junfen Fan; Haoying Xu; Linyuan Fan; Hongling Li; Robert Chunhua Zhao
• Keywords: 0303 health sciences; RNA Stability; Blotting, Western; Endoderm; Fluorescent Antibody Technique; Cell Differentiation; Mesenchymal Stem Cells; Article; Heterogeneous-Nuclear Ribonucleoproteins; Mass Spectrometry; Cell Line; Adult Stem Cells; 03 medical and health sciences; Humans; RNA, Long Noncoding; Cells, Cultured; Inhibitor of Differentiation Protein 2; Polypyrimidine Tract-Binding Protein

Abstract The generation of definitive endoderm (DE) cells in sufficient numbers is a prerequisite for cell-replacement therapy liver and pancreatic diseases. Previously, we reported that human adipose-derived mesenchymal stem (hAMSCs) can be induced to DE lineages subsequent functional cells. Clarifying the regulatory mechanisms underlying fate conversion from hAMSCs helpful developing new strategies improve differentiation efficiency organs. Long noncoding RNAs (lncRNAs) have been shown play pivotal roles developmental processes, including cell determination differentiation. In this study, profiled expression changes lncRNAs found antidifferentiation RNA ( ANCR ) was downregulated during both embryonic (ESCs) knockdown resulted elevated markers hAMSCs, but not ESCs. overexpression reduced differentiate into Inhibitor DNA binding 2 ID2 notably after knockdown. enhanced differentiation, whereas impaired process hAMSCs. interacts with RNA-binding polypyrimidine tract-binding protein 1 (PTBP1) facilitate its association mRNA, leading increased mRNA stability. Thus, /PTBP1/ network restricts toward DE. Our work highlights inherent discrepancies between Defining hAMSC-specific signaling pathways might important designing optimal protocols directing