Protein markers associated bone marrow stem cell differentiation into early progentior cells

Abstract

A novel cytosolic 58 kd phosphoprotein induced during bone marrow stem cell (BM) differentiation into dendritic cells (DC) during in vitro cultivation with the cytokine GM-CSF by addition of antisera to an 82 kd BM cell surface protein generating cultivatable dendritic progenitor cells (DP). Genes, methods for preparing them as well as early DP have been provided. Potential uses/advantages lie in the study of BM differentiation and innate immunity due to stimulatory/inhibitory DC, contribution of BM and DP to inflammation during infection and carcinogenesis, tumor promotion/regression, identification of BM-derived blood cells, T-cell activation/regulation/tolerance and inflammation.

1 . (canceled) 
     
     
         2 . (canceled) 
     
     
         3 . (canceled) 
     
     
         4 . (canceled) 
     
     
         5 . (canceled) 
     
     
         6 . (canceled) 
     
     
         7 . (canceled) 
     
     
         8 . A method of inducing expression of DP58 which comprises incubating BM cells with anti-DC antibodies. 
     
     
         9 . The method of  claim 8  in which early progenitor undifferentiated DCs are generated. 
     
     
         10 . An isolated BM cell surface protein which, in BM cells, is activated by anti-DC sera to induce expression of DP58 and that comprises the sequence of SEQ ID NO: 2. 
     
     
         11 . The CSP of  claim 10  that has a molecular weight of 82 KD. 
     
     
         12 . The CSP of  claim 10  that has the sequence: 
       
         
           
                 
               
                     1 MRLLIPSLIF LEALGLCLAK ATTVRWCAVS NSEEEKCLRW  
                 
                       QNEMRKVGGP 
                 
                     
                 
                    51 PLSCVKKSST RQCIQAIVTN RADAMTLDGG TMFDAGKPPY  
                 
                       KLRPVAAEVY 
                 
                     
                 
                   101 GTKEQPRTHY YAVAVVKNSS NFHLNQLQGL RSCHTGIGRS  
                 
                       AGWKIPIGTL 
                 
                     
                 
                   151 RPYLNWNGPP ASLEEAVSKF FSKSCVPGAQ KDRFPNLCSS  
                 
                       CAGTGANKCA 
                 
                     
                 
                   201 SSPEEPYSGY AGALRCLRDN AGDVAFTRGS TVFEELPNKA  
                 
                       ERDQYKLLCP 
                 
                     
                 
                   251 DNTWKPVTEY KECHLAQVPS HAVVSRSTND KEEAIWELLR  
                 
                       QSQEKFGKKQ 
                 
                     
                 
                   301 ASGFQLFASP SGQKDLLFKE SAIGFVRVPQ KVDVGLYLTF  
                 
                       SYTTSIQNLN 
                 
                     
                 
                   351 KKQQDVIASK ARVTWCAVGS EEKRKCDQWN RDSRGRVTCI  
                 
                       SFPTTEDCIV 
                 
                     
                 
                   401 AIMKGDADAM SLDGGYIYTA GKCGLVPVLA ENQKSSKSNG  
                 
                       LDCVNRPVEG 
                 
                     
                 
                   451 YLAVAAVRRE DAGFTWSSLR GKKSCHTAVD RTAGWNIPMG  
                 
                       LLANQTRSCK 
                 
                     
                 
                   501 FNEFFSQSCA PGADPKSNLC ALCIGDEKGE NKCAPNSKER  
                 
                       YQGYTGALRC 
                 
                     
                 
                   551 LAEKAGNVAF LKDSTVLQNT DGKNTEEWAR NLKLKDFELL  
                 
                       CLDDTRKPVT 
                 
                     
                 
                   601 EAKNCHLAIA PNHAVVSRTD KVEVLQQVVL DQQVQFGRNG  
                 
                       QRCPGEFCLF 
                 
                     
                 
                   651 QSKTKNLLFN DNTECLAKIP GKTTSEKYLG KEYVIATERL  
                 
                       KQCSSSPLLE 
                 
                     
                 
                   701 ACAFLTQ 
                 
             
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         13 . (canceled) 
     
     
         14 . (canceled) 
     
     
         15 . (canceled) 
     
     
         16 . The method of  claim 9  which comprises: (a) isolating BM stem cells with panning on anti-CSP82 kd coated plates, (b) generating DP58+ cells (BM4) by stimulation with anti-CSP82, and (c) inducing DCs by further incubation in GM-CSF in a shorter period than necessary without this step. 
     
     
         17 . (canceled) 
     
     
         18 . (canceled) 
     
     
         19 . A method of suppressing expression of a marker of BM stem cell differentiation that comprises suppressing expression of DP58 with antisense DP58 DNA or RNA.