Flattop (FLTP) is a novel biomarker for beta cell maturation

Patent metadata

Field	Value
Publication number	US-10520494-B2
Application number	US-201515126623-A
Country	US
Kind code	B2
Filing date	Mar 26, 2015
Priority date	Mar 26, 2014
Publication date	Dec 31, 2019
Grant date	Dec 31, 2019

Abstract

The present invention relates to the use of the biomarker Flattop (Fltp) for distinguishing mature β cells from immature progenitor β cells. The present invention further relates to a method for distinguishing a mature β cell from an immature progenitor β cell, the method comprising: determining the presence or absence of the biomarker Flattop (Fltp) in a β cell; wherein the presence of Fltp in the cell indicates that the cell is a mature β cell and wherein the absence of Fltp in the cell indicates that the cell is an immature progenitor β cell. Furthermore, the present invention relates to a method of identifying a compound suitable for differentiating immature progenitor β cells into mature β cells as well as to a method of identifying a compound suitable for preventing the de-differentiating of mature β cells.

First claim

The invention claimed is:

1. A method of identifying a compound suitable for differentiating immature progenitor β cells into mature β cells, the method comprising:
(a) contacting a cell population comprising immature progenitor β cells with a test compound; and
(b) subsequently determining the presence or expression level of the biomarker Flattop (Fltp) in the β cells comprised in the cell population;

wherein the presence of Fltp, or an increased expression level of Fltp, in the cells comprised in the cell population after the contacting with the test compound is indicative of a compound suitable for differentiating immature progenitor β cells into mature β cells.

2. A method of identifying a compound suitable for preventing the de-differentiation of mature β cells, the method comprising:
(a) culturing a cell population comprising mature β cells in the presence of a test compound, wherein the cells are cultured under conditions that induce the de-differentiation of said mature β cells; and
(b) subsequently determining the expression level of the biomarker Flattop (Fltp) in the cells cultured in step (a), wherein an expression level of Fltp determined in step (b) that is substantially identical to the expression level of Fltp in the cell population comprising mature β cells prior to the culture in step (a) is indicative of a compound suitable for preventing the de-differentiation of mature β cells.

3. The method according to claim 1 or 2 , wherein the test compound is a compound that activates planar cell polarity (PCP).

4. The method according to claim 3 , wherein the compound that activates planar cell polarity (PCP) is an activator of the non-canonical Wnt/PCP pathway.

5. A method for distinguishing mature β cells from immature progenitor β cells, the method comprising:
determining the presence or absence of the biomarker Flattop (Fltp) in a β cell, comprising subjecting the β cell to a process that detects the presence or absence of a Fltp protein or nucleic acid in the β cell;
wherein the presence of the Fltp protein or nucleic acid in the cell indicates that the cell is a mature β cell and wherein the absence of the Fltp protein or nucleic acid in the cell indicates that the cell is an immature progenitor β cell; and
separating the immature progenitor β cells from the mature β cells.

6. The method according to claim 5 , wherein the presence or absence of a Fltp protein or nucleic acid is determined (i) on the nucleic acid level, (ii) on the amino acid level, or (iii) a combination thereof.

7. The method of claim 6 , further comprising inducing the expression of Fltp in the cell population comprising immature progenitor cells, wherein the expression of Fltp in the cells is induced in the presence of a compound that induces the non-canonical Wnt/PCP pathway.

8. The method of claim 7 , wherein the compound that induces the non-canonical Wnt/PCP pathway is Wnt5a or Wnt4.

9. The method of claim 5 , further comprising inducing the expression of Fltp in the cell population comprising immature progenitor cells, wherein the expression of Fltp in the cells is induced in the presence of a compound that induces the non-canonical Wnt/PCP pathway.

10. The method of claim 9 , wherein the compound that induces the non-canonical Wnt/PCP pathway is Wnt5a or Wnt4.

Assignees

• Helmholtz Zentrum Muenchen—Deutsches Forschungszentrum Fuer Gesundheit Und Umwelt Gmbh
• Helmholtz Zentrum Muenchen Deutsches Forschungszentrum Gesundheit & Umwelt Gmbh

Inventors

• Lickert Heiko
• Migliorini Adriana
• Gegg Moritz
• Bader Erik

Classifications

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title

• G01N2800/042

  Disorders of carbohydrate metabolism, e.g. diabetes, glucose metabolism · CPC title

• A61K38/1709

  from mammals · CPC title

• G01N33/56966

  Animal cells · CPC title

• C12Q1/6881

  for tissue or cell typing, e.g. human leukocyte antigen [HLA] probes · CPC title