Peking University

Hong Guan Ltd.

Beihao Stem Cell and Regenerative Medicine Research Institute Co., Ltd.

Beijing Ruipu Chenchuang Technology Co., Ltd.

Beihao Stem Cell and Regenerative Medicine Research Institutes Co., Ltd.

Beijing Hua Yuan Bo Chuang Technology Limited

Beijing Vitalstar Biotechnology Co., Ltd.

Beihao Stem Cell and Regenerative Medicine Translational Research Institute

Hongkui Deng

Xu Zhang

Jing Li

Jun Xu

Yang Zhao

Yan Shi

Jingyang Guan

Yang Yang

Honggang Li

Chun Yen Liu

Wei Jiang

Jinlin Wang

Huan Yang

Bei Liu

Ming Yin

Yao Fu

Zhen Liang

Defang Liu

Yuanyuan Du

Xiaomin Du

Yantao Ma

Mingxiao Ding

Haisong Liu

Lingling Hou

Dicong Zhu

Fuchou Tang

Nan Song

Jun Jia

Xiaohan Zuo

Chengang Xiang

Pingping Hou

Ting Zhao

Yanqin Li

Junqing Ye

Provided are chemical inducers of pluripotency (CIP) which include glycogen synthase kinase inhibitors, TGFβ receptor inhibitors, cyclic AMP agonists and S-adenosylhomocysteine hydrolase (SAH) inhibitors or histone acetylators. A method of inducing pluripotency in a partially or completely differentiated cell by using such chemical inducers of pluripotency is also provided. The method includes: (i) contacting a cell with the CIPs for a sufficient period of time to result in reprograming the cell into a pluripotent stem cell having ESC-like characteristics (CiPSC). Isolated chemically induced pluripotent stem cells (CiPSCs) and their progeny, produced by inducing differentiation of the CiPSCs, can be used in a number of applications, including but not limited to cell therapy and tissue engineering.

Methods for reprograming non-pluripotent cells into pluripotent stem cells

Provided are chemical inducers of lineage reprogramming (CiLR) which include glycogen synthase kinase inhibitors, TGFβ receptor inhibitors, cyclic AMP agonists or histone acetylators. Also provided is a method of inducing lineage reprograming in a partially or completely differentiated cell of a first type into a cell with characteristics of a second and different lineage. The method includes: contacting a cell with the CiLR for a sufficient period of time to result in reprograming the cell into a modified XEN-like cell which is subsequently programmed into a cell with characteristics of a second and different lineage.

Methods for chemically induced lineage reprogramming

A method for inducing reprogramming of a cell of a first type which is not a non-hepatocyte (non-hepatocyte cell), into a cell with functional hepatic drug metabolizing and transporting capabilities, is disclosed. The non-hepatocyte is induced to express or overexpress hepatic fate conversion and maturation factors, cultured in somatic cell culture medium, hepatocyte cell culture medium and hepatocyte maturation medium for a sufficient period of time to convert the non-hepatocyte cell into a cell with hepatocyte-like properties. The iHeps induced according to the methods disclosed herein are functional induced hepatocytes (iHeps) in that they express I and II drug-metabolizing enzymes and phase III drug transporters and show superior drug metabolizing activity compared to iHeps obtained by prior art methods. The iHeps thus provide a cell resource for pharmaceutical applications.

Methods for reprograming non-hepatocyte cells into hepatocyte cells

Factors for extending the ability of isolated pluripotent stem cells to generate extraembryonic lineages in vivo, following in vitro culture, herein, chemical extenders of pluripotency (CEP). Methods of extending the ability of a pluripotent cell to generate embryonic and extraembryonic lineages. The cell to be reprogrammed is contacted with effective amounts of the CEPs for a sufficient period of time to reprogram the cell into a chemically induced extended pluripotent cell (ciEPSC). ciEPSC are identified as an extended pluripotent cell based on properties including: (i) morphologically and (ii) functionally for example, based on their ability contribute to both TE and ICM, in vivo. The ciEPSCs can be cultured or induced to differentiate into cells of a desired type, and used in a number of applications, including but not limited to cell therapy and tissue engineering.

Induced extended pluripotent stem cells, method of making and using

SUSD2 protein is used as a marker in identification, selection or separation of pancreatic internal secretion precursor cells and/or newborn pancreatic internal secretion cells; and a use of an mRNA, for encoding the SUSD2 protein, of a precursor protein as the marker in identification of the pancreatic internal secretion precursor cells and/or the newborn pancreatic internal secretion cells. Analysis of gene expression of pancreatic endoderm cells sourced by induced directional differentiation of human pluripotent stem cells finds the enrichment expression of a SUSD2 gene in the pancreatic internal secretion precursor cells and the newborn pancreatic internal secretion cells. A protein encoded by the SUSD2 gene is a receptor protein on cell membranes. Using the protein as the marker, the identification, the selection or the separation of the pancreatic internal secretion precursor cells and the newborn pancreatic internal secretion cells can be conducted.

Use of SUSD2 protein as marker

Cocktails of chemical inducers of neuron-like properties (CINP) is provided, which includes cAMP agonists, neurogenic small molecules, glycogen synthase kinase inhibitors, TGF&#x3b2; receptor inhibitors, and BET family bromodomain inhibitors and optionally, a selective inhibitor of ROCK or p38 MAPK. These cocktails are used in a method of inducing neuron-like properties in partially or completely differentiated non-neuronal cells. The method includes contacting cells of a first type (non-neuronal) with the CINPs for a sufficient period of time to result in reprogramming the cell into cells of a second type having neuron-like characteristics (CiNs). Isolated chemically induced neurons (CiNs) can be used in a number of applications, including but not limited to cell therapy.

Compositions and methods for reprogramming non-neuronal cells into neuron-like cells

The invention provides a composition and a method for inducing pluripotency in non-pluripotent eukaryotic cells. The composition comprises chemical inducers of pluripotency (CIPs) including glycogen synthase kinase (GSK) inhibitors, TGFp receptor inhibitors, cyclic AMP agonists, S-adenosylhomocysteine hydrolase (SAH) inhibitors, and optionally an agent that promotes histone acetylation. The method comprises contacting a cell with the CIPs for a sufficient period of time to reprogram the cell into a pluripotent stem cell.

Compositions and methods for reprograming non-pluripotent cells into pluripotent stem cells

The present invention provided a simple three-step approach based on the combinational induction with activin A, all-trans retinoic acid and, optionally, other maturation factors which are able to induce embryonic stem cells to differentiate into insulin-producing cells. A kit used to induce embryonic stem cells to differentiate into insulin-producing cells was also provided.

Method of inducing embryonic stem cells into pancreatic cells

Growing community of inventors

Beijing, China

Hongkui Deng