0 24 Erythropoietin-dependent erythropoietin-dependent JJ 25 34 induction induction NN 35 37 of of IN 38 48 hemoglobin hemoglobin NN 49 58 synthesis synthesis NN 59 61 in in IN 62 63 a a DT 64 82 cytokine-dependent cytokine-dependent JJ 83 87 cell cell NN 88 92 line line NN 93 98 M-TAT m-tat NN 98 99 . . . 101 106 M-TAT m-tat NN 107 109 is be VBZ 110 111 a a DT 112 130 cytokine-dependent cytokine-dependent JJ 131 135 cell cell NN 136 140 line line NN 141 145 with with IN 146 149 the the DT 150 159 potential potential NN 160 162 to to TO 163 176 differentiate differentiate VB 177 182 along along IN 183 186 the the DT 187 196 erythroid erythroid JJ 197 200 and and CC 201 215 megakaryocytic megakaryocytic JJ 216 224 lineages lineage NNS 224 225 . . . 226 228 We we PRP 229 237 cultured culture VBD 238 243 M-TAT m-tat NN 244 249 cells cell NNS 250 254 long long JJ 255 259 term term NN 260 261 ( ( ( 261 262 > > SYM 263 264 1 1 CD 265 269 year year NN 269 270 ) ) ) 271 273 in in IN 274 277 the the DT 278 288 continuous continuous JJ 289 297 presence presence NN 298 300 of of IN 301 315 erythropoietin erythropoietin NN 316 317 ( ( ( 317 320 EPO EPO NNP 320 321 ) ) ) 321 322 , , , 323 345 granulocyte-macrophage granulocyte-macrophage JJ 346 364 colony-stimulating colony-stimulating JJ 365 371 factor factor NN 372 373 ( ( ( 373 379 GM-CSF GM-CSF NNP 379 380 ) ) ) 380 381 , , , 382 384 or or CC 385 389 stem stem NN 390 394 cell cell NN 395 401 factor factor NN 402 403 ( ( ( 403 406 SCF SCF NNP 406 407 ) ) ) 407 408 . . . 409 414 These these DT 415 419 long long JJ 420 424 term term NN 425 433 cultures culture NNS 434 437 are be VBP 438 446 referred refer VBN 447 449 to to TO 450 452 as as IN 453 462 M-TAT/EPO M-TAT/EPO NNP 462 463 , , , 464 476 M-TAT/GM-CSF M-TAT/GM-CSF NNP 476 477 , , , 478 481 and and CC 482 491 M-TAT/SCF M-TAT/SCF NNP 492 497 cells cell NNS 497 498 , , , 499 511 respectively respectively RB 511 512 . . . 513 523 Hemoglobin hemoglobin NN 524 537 concentration concentration NN 538 541 and and CC 542 554 gamma-globin gamma-globin NN 555 558 and and CC 559 568 erythroid erythroid JJ 569 590 delta-aminolevulinate delta-aminolevulinate JJ 591 599 synthase synthase NN 600 604 mRNA mrna NN 605 611 levels level NNS 612 616 were be VBD 617 630 significantly significantly RB 631 637 higher high JJR 638 640 in in IN 641 650 M-TAT/EPO M-TAT/EPO NNP 651 656 cells cell NNS 657 661 than than IN 662 664 in in IN 665 677 M-TAT/GM-CSF M-TAT/GM-CSF NNP 678 683 cells cell NNS 683 684 . . . 685 689 When when WRB 690 693 the the DT 694 706 supplemented supplement VBN 707 715 cytokine cytokine NN 716 719 was be VBD 720 728 switched switch VBN 729 733 from from IN 734 740 GM-CSF GM-CSF NNP 741 743 to to TO 744 747 EPO EPO NNP 747 748 , , , 749 759 hemoglobin hemoglobin NN 760 769 synthesis synthesis NN 770 772 in in IN 773 785 M-TAT/GM-CSF M-TAT/GM-CSF NNP 786 791 cells cell NNS 792 801 increased increase VBD 802 809 rapidly rapidly RB 810 811 ( ( ( 811 817 within within IN 818 819 5 5 CD 820 821 h h NN 821 822 ) ) ) 822 823 , , , 824 827 and and CC 828 831 the the DT 832 837 level level NN 838 840 of of IN 841 847 GATA-1 GATA-1 NNP 848 852 mRNA mRNA NNP 853 862 increased increase VBD 862 863 . . . 864 866 In in IN 867 875 contrast contrast NN 875 876 , , , 877 880 the the DT 881 889 addition addition NN 890 892 of of IN 893 899 GM-CSF GM-CSF NNP 900 902 to to TO 903 906 the the DT 907 916 M-TAT/EPO M-TAT/EPO NNP 917 921 cell cell NN 922 929 culture culture NN 930 939 decreased decrease VBD 940 943 the the DT 944 950 amount amount NN 951 953 of of IN 954 964 hemoglobin hemoglobin NN 964 965 , , , 966 970 even even RB 971 973 in in IN 974 977 the the DT 978 986 presence presence NN 987 989 of of IN 990 993 EPO EPO NNP 993 994 , , , 995 1005 indicating indicate VBG 1006 1010 that that IN 1011 1014 the the DT 1015 1018 EPO EPO NNP 1019 1025 signal signal NN 1026 1029 for for IN 1030 1039 erythroid erythroid JJ 1040 1055 differentiation differentiation NN 1056 1058 is be VBZ 1059 1069 suppressed suppress VBN 1070 1072 by by IN 1073 1079 GM-CSF GM-CSF NNP 1079 1080 . . . 1081 1085 Thus thus RB 1085 1086 , , , 1087 1096 erythroid erythroid JJ 1097 1108 development development NN 1109 1111 of of IN 1112 1117 M-TAT M-TAT NNP 1118 1123 cells cell NNS 1124 1126 is be VBZ 1127 1135 promoted promote VBN 1136 1138 by by IN 1139 1142 EPO EPO NNP 1143 1146 and and CC 1147 1157 suppressed suppress VBN 1158 1160 by by IN 1161 1167 GM-CSF GM-CSF NNP 1167 1168 . . . 1169 1174 These these DT 1175 1182 results result NNS 1183 1190 support support VBP 1191 1194 the the DT 1195 1205 hypothesis hypothesis NN 1206 1210 that that IN 1211 1214 EPO EPO NNP 1215 1223 actively actively RB 1224 1234 influences influence VBZ 1235 1238 the the DT 1239 1250 programming programming NN 1251 1253 of of IN 1254 1258 gene gene NN 1259 1269 expression expression NN 1270 1278 required require VBN 1279 1282 for for IN 1283 1292 erythroid erythroid JJ 1293 1303 progenitor progenitor NN 1304 1308 cell cell NN 1309 1324 differentiation differentiation NN 1324 1325 . . .