Polypeptide having an activity to support proliferation or survival of hematopoietic stem cell and hematopoietic progenitor cell, and DNA coding for the same

Abstract

A gene encoding a polypeptide having an activity to support proliferation or survival of hematopoietic stem cells or hematopoietic progenitor cells is isolated by comparing expressed genes between cells which support proliferation or survival of hematopoietic stem cells or hematopoietic progenitor cells and cells which do not support the proliferation or survival. Proliferation or survival of hematopoietic stem cells or hematopoietic progenitor cells is supported by using stromal cells in which the isolated gene is expressed or a gene product of the isolated gene.

1 . An isolated DNA molecule comprising a nucleotide sequence encoding a polypeptide, wherein the polypeptide comprises:
 (a) the amino acid sequence of SEQ ID NO:19;   (b) the amino acid sequence of SEQ ID NO:25; or   (c) the amino acid sequence of (a) or (b) which includes a deletion, substitution or insertion of one or several amino acids and which has an activity to support proliferation or survival of hematopoietic stem cells or hematopoietic progenitor cells.   
     
     
         2 . The DNA molecule of  claim 1 , wherein the DNA molecule comprises a nucleotide sequence of (a) nucleotides 1 to 444 of SEQ ID NO: 18, (b) nucleotides 132 to 506 of SEQ ID NO: 24, or (c) a nucleotide sequence that hybridizes to a nucleotide sequence as defined in (a) or (b) under one of the following stringent conditions:
 (1) wash in 6×SSC, 5×Denhardt, 0.5% SDS at 68° C. or   (2) wash in 6×SSC, 5×Denhardt, 0.5% SDS 50% formamide at 42° C.; and wherein the nucleotide sequence of (c) encodes a polypeptide having an activity to support proliferation or survival of hematopoietic stem cells or hematopoietic progenitor cells.   
     
     
         3 . The DNA molecule of  claim 1 , wherein the DNA molecule comprises a nucleotide sequence encoding a polypeptide comprising the amino acid sequence of SEQ ID NO: 19 or the amino acid sequence of SEQ ID NO:25. 
     
     
         4 . An expression vector comprising the DNA of  claim 1  and a gene expression regulatory sequence. 
     
     
         5 . An isolated cell comprising the DNA molecule of  claim 4 . 
     
     
         6 . An isolated polypeptide encoded by the DNA molecule of  claim 1 , the polypeptide having an activity to support proliferation or survival of hematopoietic stem cells or hematopoietic progenitor cells. 
     
     
         7 . The polypeptide of  claim 6 , wherein the polypeptide comprises the amino acid sequence of SEQ ID NO:19 or 25. 
     
     
         8 . The polypeptide of  claim 6 , which is modified with one or more modifying agents selected from the group consisting of polyethylene glycol (PEG), dextran, poly(N-vinyl-pyrrolidone), polypropylene glycol homopolymer, copolymer of polypropylene oxide/ethylene oxide, polyoxyethylated polyol and polyvinyl alcohol. 
     
     
         9 . An antibody which binds to the polypeptide of  claim 6 . 
     
     
         10 . The antibody of  claim 9 , wherein the antibody is a monoclonal antibody. 
     
     
         11 . A method for supporting proliferation or survival of hematopoietic stem cells 
       or hematopoietic progenitor cells, comprising the step of co-culturing stromal cells which express the DNA molecule of  claim 2  with CD-34-positive hematopoietic stem cells, under conditions that support proliferation or survival of said hematopoietic stem cells or hematopoietic progenitor cells. 
     
     
         12 . The method of  claim 10 , wherein the DNA molecule encodes a polypeptide comprising the sequence of SEQ ID NO: 19 or 25. 
     
     
         13 . A method for supporting proliferation or survival of hematopoietic stem cells 
       or hematopoietic progenitor cells, comprising the step of culturing CD-34-positive hematopoietic stem cells or erythroid progenitor cells in the presence of a polypeptide according to  claim 6 , under conditions that support proliferation or survival of said hematopoietic stem cells or hematopoietic progenitor cells. 
     
     
         14 . A method for supporting proliferation or survival of hematopoietic stem cells 
       or hematopoietic progenitor cells, comprising the step of culturing CD-34-positive hematopoietic stem cells or erythroid progenitor cells in the presence of a polypeptide according to  claim 7 , under conditions that support proliferation or survival of said hematopoietic stem cells or hematopoietic progenitor cells. 
     
     
         15 . A composition having an effect to support proliferation or survival of hematopoietic stem cells or hematopoietic progenitor cells, which comprises an effective amount of a polypeptide according to  claim 6 . 
     
     
         16 . A composition having an effect to support proliferation or survival of hematopoietic stem cells or hematopoietic progenitor cells, which comprises an effective amount of a polypeptide according to  claim 7 . 
     
     
         17 . A composition comprising the polypeptide of  claim 6 . 
     
     
         18 . A composition comprising the polypeptide of  claim 7 .