title: Pdx1 protein induces human embryonic stem cells into the pancreatic endocrine lineage.
abstract: Success in generating insulin-producing cells (IPCs) from human embryonic stem (hES) cells by genetic manipulation has recently revealed a new therapeutic potential for diabetes. However, clinical application has been hampered by the viral genome integration and the risk of insertion mutagenesis that are entailed. Herein, we report the induction of hEC into IPCs by direct delivery of human Pdx1 proteins per se. Recombinant human Pdx1 proteins (hPdx1), which have an Antennapedia-like protein transduction domain sequence in their structure, can be efficiently translocated into hES cells and function as pancreatic transcription factor. hPdx1 protein activates a group of genes related to pancreatic beta-cell lineage development in hES cells, including NeuroD1, Nkx2.2, Pax4, Pax6, Nkx6.1 and Isl-1. hPdx1-treated hES cells synthesise and release insulin in response to glucose challenge. Therefore, this study constitutes a proof-of-concept demonstration of protein-mediated pancreatic specific differentiation of the hES cells by exploiting specific intrinsic properties of the hPdx1 protein.
authors: Hubei Key Laboratory of Clinic Centre, Tai-He Hospital, Hubei University of Medicine, 32 S Renmin Road, Shiyan, Hubei 442000, China. liangqingle@gmail.com
authors: Qing Le
authors: QL
authors: Liang
authors: Zhengying
authors: Z
authors: Mo
authors: Xue Feng
authors: XF
authors: Li
authors: Xiao Xun
authors: XX
authors: Wang
authors: Rui Ming
authors: RM
authors: Li
mesh_terms: D002454:Cell Differentiation; D002460:Cell Line; D019070:Cell Lineage; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism; D000090322:Homeobox Protein Nkx-2.2; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D050417:Insulin-Secreting Cells / Q000166:cytology* / Q000378:metabolism; D009687:Nuclear Proteins; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D000090322:Homeobox Protein Nkx-2.2; D018398:Homeodomain Proteins; C000715631:NKX2-2 protein, human; D009687:Nuclear Proteins; D015534:Trans-Activators; D014157:Transcription Factors; C084010:pancreatic and duodenal homeobox 1 protein