Polypeptide having an activity to support proliferation or survival of hematopoietic stem cell or 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 . A DNA coding a polypeptide wherein the polypeptide comprises:
 (A) the amino acid sequence of SEQ ID NO: 48; or   (B) an amino acid sequence including deletion, substitution or insertion of one or several amino acids in the amino acid sequence as defined in (A),   
       wherein the polypeptide has an activity to support hematopoietic stem cell or hematopoietic progenitor cell proliferation or survival. 
     
     
         2 . The DNA according to  claim 1 , comprising:
 (A) the nucleotides 18 to 746 of SEQ ID NO: 47; or   (B) a nucleotide sequence which hybridizes under stringent conditions to nucleotides 18 to 744 of SEQ ID NO: 47,   
       wherein the DNA encodes a polypeptide having an activity to support hematopoietic stem cell or hematopoietic progenitor cell proliferation or survival. 
     
     
         3 . The DNA according to  claim 2 , wherein the stringent condition is 6×SSC, 5×Denhardt, 0.5% SDS and 68° C., or 6×SSC, 5×Denhardt, 0.5% SDS, 50% formamide and 42° C. 
     
     
         4 . An expression vector which comprises the DNA of any one of  claims 1  or  2  in such a manner that the DNA can be expressed. 
     
     
         5 . An isolated cell into which the DNA of any one of  claims 1  or  2  is introduced in such a manner that the DNA can be expressed. 
     
     
         6 . A monoclonal antibody which binds to a polypeptide which is an expression product of the nucleic acid of SEQ ID NO: 47. 
     
     
         7 . A monoclonal antibody which binds to a polypeptide having the amino acid sequence of SEQ ID NO: 48. 
     
     
         8 . A method for supporting hematopoietic stem cell or hematopoietic progenitor cell proliferation or survival, comprising the step of co-culturing stromal cells comprising a DNA encoding a polypeptide under conditions in which the polypeptide is expressed, with hematopoietic stem cells or progenitor cells, wherein the polypeptide comprises:
 (A) the amino acid sequence of SEQ ID NO: 48; or   (B) an amino acid sequence including deletion, substitution or insertion of one or several amino acids in the amino acid sequence of SEQ ID NO: 48,   
       wherein the polypeptide has an activity to support hematopoietic stem cell or hematopoietic progenitor cell proliferation or survival. 
     
     
         9 . The method according to  claim 8 , wherein the DNA comprises:
 (A) the nucleotide sequence of nucleotides 18 to 746 of SEQ ID NO: 47; or   (B) a nucleotide sequence that hybridizes under stringent conditions to nucleotides 18-746 of SEQ ID NO: 47,   
       wherein the polynucleotide encodes a polypeptide having activity to support hematopoietic stem cell or hematopoietic progenitor cell proliferation or survival. 
     
     
         10 . A method for supporting hematopoietic stem cell or hematopoietic progenitor cell proliferation or survival comprising culturing hematopoietic stem cells or progenitor cells in the presence of a polypeptide, wherein said polypeptide has an activity to support hematopoietic stem cell or hematopoietic progenitor cell proliferation or survival when the hematopoietic stem cells or hematopoietic progenitor cells are cultured in the presence of the polypeptide, said polypeptide comprising:
 (A) the amino acid sequence of SEQ ID NO: 48; or   (B) an amino acid sequence including deletion, substitution or insertion of one or several amino acids in the amino acid sequence of SEQ ID NO: 48,   
       wherein said polypeptide has activity to support hematopoietic stem cell or hematopoietic progenitor cell proliferation or survival.