53 results about "PDX1" patented technology

Disclosed herein are cell cultures comprising PDX1-positive endoderm cells and methods of producing the same. Also disclosed herein are cell populations comprising substantially purified PDX1-positive endoderm cells as well as methods for enriching, isolating and purifying PDX1-positive endoderm cells from other cell types. Methods of identifying differentiation factors capable of promoting the differentiation of endoderm cells, such as PDX1-positive foregut endoderm cells and PDX1-negative definitive endoderm cells, are also disclosed.

Disclosed herein are cell cultures comprising dorsal and / or ventral PDX1-positive foregut endoderm cells and methods of producing the same. Also disclosed herein are cell populations comprising substantially purified dorsal and / or ventral PDX1-positive foregut endoderm cells as well as methods for enriching, isolating and purifying dorsal and / or ventral PDX1-positive foregut endoderm cells from other cell types. Methods of identifying differentiation factors capable of promoting the differentiation of dorsal and / or ventral PDX1-positive foregut endoderm cells, are also disclosed.

The invention discloses a method using CRISPR-Cas9 to specifically knock off pig PDX1 gene and sgRNA of PDX1 gene for specific targeting. The target sequence of sgRNA of PDX1 gene for specific targeting on PDX1 gene is accord with the sequence alignment rule of 5'-N(20)NGG-3', wherein N(20) represents 20 continuous bases, and each N represent A, T, C or G; the target sequence of PDX1 gene is arranged in the first exon coding region on the N terminal of PDX1 gene or a junction between the coding region and neighbored intron, and the target sequence of PDX1 gene is unique. The provided method can rapidly, precisely, efficiently and specifically knock off PDX1 gene of pigs, and solves the problems of long period and high cost of pig PDX1 gene knocking.

Disclosed herein are cell cultures comprising PDX1-positive endoderm cells and methods of producing the same. Also disclosed herein are cell populations comprising substantially purified PDX1-positive endoderm cells as well as methods for enriching, isolating and purifying PDX1-positive endoderm cells from other cell types. Methods of identifying differentiation factors capable of promoting the differentiation of endoderm cells, such as PDX1-positive foregut endoderm cells and PDX1-negative definitive endoderm cells, are also disclosed.

The invention provides pluripotent cells modified to overexpress Pdx1 and Ngn3. Pluripotent cells include embryonic stem cells and induced pluripotent stem cells. Methods of producing pancreatic endocrine progenitor cells from ES cells or from iPS cells by forced expression of Pdx1 and Ngn3 are provided. Pancreatic endocrine progenitor cells are useful for drug discovery and cell replacement therapy.

Disclosed herein are cell cultures comprising dorsal and / or ventral PDX1-positive foregut endoderm cells and methods of producing the same. Also disclosed herein are cell populations comprising substantially purified dorsal and / or ventral PDX1-positive foregut endoderm cells as well as methods for enriching, isolating and purifying dorsal and / or ventral PDX1-positive foregut endoderm cells from other cell types. Methods of identifying differentiation factors capable of promoting the differentiation of dorsal and / or ventral PDX1-positive foregut endoderm cells, are also disclosed.

Disclosed herein are cell cultures comprising PDX1-positive endoderm cells and methods of producing the same. Also disclosed herein are cell populations comprising substantially purified PDX1-positive endoderm cells as well as methods for enriching, isolating and purifying PDX1-positive endoderm cells from other cell types. Methods of identifying differentiation factors capable of promoting the differentiation of endoderm cells, such as PDX1-positive foregut endoderm cells and PDX1-negative definitive endoderm cells, are also disclosed.

Disclosed herein are cell cultures comprising PDX1-positive endoderm cells and methods of producing the same. Also disclosed herein are cell populations comprising substantially purified PDX1-positive endoderm cells as well as methods for enriching, isolating and purifying PDX1-positive endoderm cells from other cell types. Methods of identifying differentiation factors capable of promoting the differentiation of endoderm cells, such as PDX1-positive foregut endoderm cells and PDX1-negative definitive endoderm cells, are also disclosed.

The invention provides for methods of differentiating pancreatic endocrine cells into pancreatic beta cells expressing PDX1, NKX6.1, MAFA, UCN3 and SLC2A. These pancreatic beta cells may be obtained by step-wise differentiation of pluripotent stem cells. The pancreatic beta cells exhibit glucose-dependent mitochondrial respiration and glucose-stimulated insulin secretion similar to islet cells.

Purified preparations of human embryonic stem cells with certain population-specific characteristics are disclosed. This preparation is characterized by the positive expression of the following pluripotent cell surface markers: SSEA-1 (−); SSEA-4 (+); TRA-1-60 (+); TRA-1-81 (+); alkaline phosphatase (+), as well as a set of ES cell markers including Oct-4, Nanog, Rex1, Sox2, Thy1, FGF4, ABCG2, Dppa5, UTF1, Cripto1, hTERT, Connexin-43 and Connexin-45. The cells of the preparation are negative for lineage specific markers like Keratin 8, Sox-1, NFH (ectoderm), MyoD, brachyury, cardiac-actin (mesoderm), HNF-3 beta, albumin, and PDX1 (endoderm). The cells of the preparation are human embryonic stem cells, have normal karyotypes, exhibit high telomerase activity and continue to proliferate in an undifferentiated state after continuous culture for over 40 passages. The embryonic stem cell line Relicell™ hES1 also retains the ability, throughout the culture, to differentiate into cell and tissue types derived from all three embryonic germ layers (endoderm, mesoderm and ectoderm). Methods for isolating a human embryonic stem cell line are also disclosed.

Methods and devices for culturing human pluripotent stem cells to produce cells of the pancreatic lineage are disclosed. The methods include steps of culturing the stem cells under conditions that induce the expression of mesendoderm / primitive streak and definitive endoderm markers in a chemically defined medium including an effective amount of i) fibroblast growth factor, ii) Activin A, and iii) bone morphogenetic protein. The methods further include the steps of culturing cells under conditions favoring the formation of at least one of intact embryoid bodies and pancreatic progenitor PDX1+Ins− cells.

Disclosed is an autologous non-human mammalian model system derived from induced pluripotent stem (iPS) cells. Also disclosed are methods of differentiating non-human primate iPS cells, which can result in populations of cells enriched for SOX2+ or PDX1+ foregut-like cells, for CDX2+ hindgut-like cells, for CD34+ hematopoietic progenitor-like cells, or epithelial-like cells. Also disclosed is a non-human primate containing an autologous cell type of interest, which is differentiated in vitro from an induced pluripotent stem cell reprogrammed from a primary somatic cell. Methods of monitoring exogenously introduced cells within a non-human mammal are also disclosed.

The present invention relates to the diagnosis of breast cancer. It discloses the use of protein PDX1 (peroxiredoxin 1) in the diagnosis of breast cancer. It relates to a method for diagnosis of breast cancer from a liquid sample, derived from an individual by measuring PDX1 in said sample. Measurement of PDX1 can, e.g., be used in the early detection or diagnosis of breast cancer.

The invention relates to a method for inducing the differentiation of mesenchymal stem cells of human embryo livers into islet beta-like cells and stably expressing insulin and special induced liquid thereof. The method comprises the following steps: separating, purifying and amplifying mesenchymal stem cells of human embryo livers; then taking out cells formed after the third generation and inducing the cells by the special induced liquid to obtain islet beta-like cell mass capable of expressing the insulin stably. The induced liquid can be obtained by adding TAT-PDX1 fusion protein in cell culture fluid. The method can realize in-vitro induction of mesenchymal stem cells of human embryo livers into islet beta-like cells capable of secreting the insulin stably. When transplanted in the body of a diabetic patient, the obtained islet beta-like cells can further adjust blood sugar level so as to realize cell therapy of diabetes. Therefore, research in the field has broad clinic application prospect and can bring greater economic benefit and social benefit.

The invention relates to the field of disease aided diagnosis, in particular to a diabetic typing kit, and discloses application of one or multiple of HNF1B gene, PDX1 gene, PAX6 gene, MADD gene, NKX2-2 gene, INSR gene, SRR gene, ND1 gene and SRIT1 gene in human whole genome in preparing diabetic typing products. The diabetic typing kit comprises a primer pair for amplifying SNP loci of one or multiple of the HNF1B gene, the PDX1 gene, the PAX6 gene, the MADD gene, the NKX2-2 gene, the INSR gene, the SRR gene, the ND1 gene or the SRIT1 gene. By the diabetic typing kit, the technical defect that current II-type diabetic typing is time-consuming, labor-consuming and incomplete can be overcome.

The invention discloses a method for obtaining pancreatic beta cells through induced differentiation of human umbilical cord mesenchymal stem cells through a gene transfer method. Pancreatic cell specific genes containing PDX1, MAFA, NGN3, FOXA2, NEUROD1 and FGF21 are used, adenovirus expression vectors of transmembrane singles are connected, various recombinant protein and small molecules are combined, and the human umbilical cord mesenchymal stem cells are induced to be directionally differentiated into the pancreatic beta cells. The inducing method is easy and convenient to implement, simple in operation and good in differentiation effect.

The invention discloses construction and application of an induced pluripotent stem cell line for expressing Pdx1 / insulin double reporting genes, and provides a method for induced directional differentiation of pluripotent stem cells into insulin beta-cells. The method comprises the following steps that (1) the pluripotent stem cells are formed into embryonic bodies; 2) the embryonic bodies are subjected to demethylation treatment, and cells subjected to demethylation treatment are obtained; and (3) the cells subjected to demethylation treatment are sequentially differentiated into endosperm cells, archenteron cells, pancreatic precursor cells, endocrine precursor cells and the insulin beta-cells. The study proves that the hiPSC line for expressing the Pdx1-mRFP / insulin-hrGFP double reporting genes has the important value in establishing and optimizing a beta-cell differentiation method.

This invention provides methods of screening for compounds that inhibit herpesviral transcription and replication. The methods comprise screening test compounds for ability to enhance the activity of homeodomain transcription factor PDX1 in repressing transcription of herpesviral genes (e.g., the IE gene of cytomegalovirus). Transcriptional repression by PDX1 can be monitored using an expression vector comprising a reporter gene operably linked to a PDX1-binding, upstream transcription regulatory sequence of the herpesvirus. The invention further provides methods and pharmaceutical compositions for stimulating PDX1-mediated transcriptional repression in a subject and for treating diseases and conditions associated with herpesviral infection.

The present invention includes compositions and methods for transforming cells into glucose-responsive, insulin-production cells using a construct that expresses betacellulin and PDX1, e.g., transforming pancreatic acinar cells using one or more expression vectors that expressed betacellulin and PDX1 using ultrasound targeted microbubble destruction (UTMD).

The invention provides a preparation method, a product and application of an alpha cell. The preparation method of the alpha cell comprises the following steps of over-expressing the following transcription factors in a somatic cell: Hhex, Foxa3, Gata4, Pdx1 and Pax4. The invention also provides the alpha cell prepared and obtained by the method and the application of the alpha cell. The invention discloses a brand-new method for obtaining the alpha cell; the alpha cell has important effects on the research and the treatment of diabetes mellitus and the application of relevant regenerative medicine; the invention also optimizes a method for preparing the alpha call; the better combination of the transcription factors is found out. The alpha cell prepared and obtained by utilizing the method provided by the invention not only has the function of a natural islet alpha cell, but also is a fungible clinical resource for treating the diabetes mellitus, which is wide in source range and is high-efficiency, stable and safe.

The invention discloses a PDX1 positive entoderm cell and a preparation method thereof. In the method, an entoderm cell which is obtained by differentiating an isolated embryonic stem cell or an isolated induction multipotential stem cell and does not express a transcription factor PDX1 is cultured to obtain the PDX1 positive entoderm cell; all trans retinoic acid is added into a system of the culture, and the cell inoculation density is 2*103 cells / square centimeter to 2*105 cells / square centimeter. The method effectively promotes the entoderm cell differentiated by the embryonic stem cell to the direction of the PDX1 positive entoderm cell, and reduces the differentiation to the direction of a liver cell. Accordingly, the method has wide application prospect in the field of induction from the human embryonic stem cell to the PDX1 positive entoderm cell.

The present invention relates to a method for obtaining Ngn3-expressing cells and insulin producing-beta cells by contacting a Pdx1-expressing pancreas explant with an amount of at least one histone deacetylase inhibitor (HDACi). The inventive methods have the advantage of being simple and quick, and of providing large amounts of Ngn3-expressing cells and insulin producing-beta cells, that are useful therapeutic tools. The invention also relates to a pharmaceutical composition for the treatment of diabetes which comprises an amount of at least one HDACi.

A self-replicating RNA for inducing somatic differentiation of unmodified adult stem cells is described. Methods of differentiating unmodified adult stem cells into functional beta-like cells are also described, as well as compositions, tissues and devices containing such cells. The method requires inducing sequential expression of PDX1 before NGN3, and NGN3 before MAFA in these stem cells to form reprogrammed beta-cells. Self-replicating RNAs are provided and introduced into the adult stem cells to induce the sequential expression. Methods of treating diabetes are also provided, comprising obtaining stem cells, preferably from a patient with diabetes, inducing sequential expression of PDX1>NGN3>MAFA, in said stem cells to form reprogrammed beta-cells, and introducing said reprogrammed beta-cells into a pancreas of said patient.

This invention provides methods of screening for compounds that inhibit herpesviral transcription and replication. The methods comprise screening test compounds for ability to enhance the activity of homeodomain transcription factor PDX1 in repressing transcription of herpesviral genes (e.g., the IE gene of cytomegalovirus). Transcriptional repression by PDX1 can be monitored using an expression vector comprising a reporter gene operably linked to a PDX1-binding, upstream transcription regulatory sequence of the herpesvirus. The invention further provides methods and pharmaceutical compositions for stimulating PDX1-mediated transcriptional repression in a subject and for treating diseases and conditions associated with herpesviral infection.

The invention discloses a method for directly reprogramming mouse hepatocyte into an islet beta cell, and an application thereof. The method for reprogramming mouse hepatocyte into the islet beta cell is characterize in that Pdx1 protein encoding gene, Pax4 protein encoding gene and Neurod1 protein encoding gene are transferred into an in vitro liver cell to obtain the islet beta cell. The method has the following advantages: 1, a non-viral Entranster TM-D transfection reagent is adopted, so high transfection efficiency is realized, and the transfection safety in the direct reprogramming process is greatly improved; 2, a new optimum transfection combination Pdx1, Pax4 and Neurod1 suitable for being used in direct reprogramming to form the islet beta cell is screened according to the literature; and 3, an optimum transfection period is screened according to the action sequence of all transcription factors, so the maturity of the directly reprogrammed islet cell is improved, and the reprogramming efficiency in the researches in the invention reaches 23%.