0 8 Evidence evidence NN 9 12 for for IN 13 21 distinct distinct JJ 22 35 intracellular intracellular JJ 36 45 signaling signaling NN 46 54 pathways pathway NNS 55 57 in in IN 58 63 CD34+ cd34+ JJ 64 74 progenitor progenitor NN 75 77 to to TO 78 87 dendritic dendritic JJ 88 92 cell cell NN 93 108 differentiation differentiation NN 109 113 from from IN 114 115 a a DT 116 121 human human JJ 122 126 cell cell NN 127 131 line line NN 132 137 model model NN 137 138 . . . 140 153 Intracellular intracellular JJ 154 161 signals signal NNS 162 166 that that WDT 167 174 mediate mediate VBP 175 190 differentiation differentiation NN 191 193 of of IN 194 205 pluripotent pluripotent JJ 206 217 hemopoietic hemopoietic JJ 218 229 progenitors progenitor NNS 230 232 to to TO 233 242 dendritic dendritic JJ 243 248 cells cell NNS 249 250 ( ( ( 250 252 DC DC NNP 252 253 ) ) ) 254 257 are be VBP 258 265 largely largely RB 266 275 undefined undefined JJ 275 276 . . . 277 279 We we PRP 280 284 have have VBP 285 295 previously previously RB 296 301 shown show VBN 302 306 that that IN 307 314 protein protein NN 315 321 kinase kinase NNP 322 323 C C NNP 324 325 ( ( ( 325 328 PKC PKC NNP 328 329 ) ) ) 330 340 activation activation NN 341 342 ( ( ( 342 346 with with IN 347 354 phorbol phorbol NN 355 360 ester ester NN 361 362 ( ( ( 362 365 PMA PMA NNP 365 366 ) ) ) 367 372 alone alone RB 372 373 ) ) ) 374 386 specifically specifically RB 387 394 induces induce VBZ 395 410 differentiation differentiation NN 411 413 of of IN 414 421 primary primary JJ 422 427 human human JJ 428 433 CD34+ cd34+ JJ 434 445 hemopoietic hemopoietic JJ 446 456 progenitor progenitor NN 457 462 cells cell NNS 463 464 ( ( ( 464 467 HPC HPC NNP 467 468 ) ) ) 469 471 to to TO 472 478 mature mature JJ 479 481 DC DC NNP 481 482 . . . 483 485 We we PRP 486 489 now now RB 490 494 find find VBP 495 499 that that IN 500 515 cytokine-driven cytokine-driven JJ 516 517 ( ( ( 517 539 granulocyte-macrophage granulocyte-macrophage JJ 540 543 CSF CSF NNP 544 547 and and CC 548 557 TNF-alpha TNF-alpha NNP 557 558 ) ) ) 559 564 CD34+ cd34+ JJ 565 573 HPC–>DC HPC–>DC NNP 574 589 differentiation differentiation NN 590 592 is be VBZ 593 607 preferentially preferentially RB 608 615 blocked block VBN 616 618 by by IN 619 629 inhibitors inhibitor NNS 630 632 of of IN 633 636 PKC PKC NNP 637 647 activation activation NN 647 648 . . . 649 651 To to TO 652 659 further further RB 660 668 identify identify VB 669 682 intracellular intracellular JJ 683 690 signals signal NNS 691 694 and and CC 695 705 downstream downstream JJ 706 712 events event NNS 713 722 important important JJ 723 725 in in IN 726 731 CD34+ cd34+ JJ 732 740 HPC–>DC HPC–>DC NNP 741 756 differentiation differentiation NN 757 759 we we PRP 760 764 have have VBP 765 778 characterized characterize VBN 779 780 a a DT 781 786 human human JJ 787 795 leukemic leukemic JJ 796 800 cell cell NN 801 805 line line NN 806 811 model model NN 812 814 of of IN 815 819 this this DT 820 827 process process NN 827 828 . . . 829 832 The the DT 833 838 CD34+ cd34+ JJ 839 853 myelomonocytic myelomonocytic JJ 854 858 cell cell NN 859 863 line line NN 864 867 KG1 kg1 NN 868 882 differentiates differentiate VBZ 883 887 into into IN 888 902 dendritic-like dendritic-like JJ 903 908 cells cell NNS 909 911 in in IN 912 920 response response NN 921 923 to to TO 924 946 granulocyte-macrophage granulocyte-macrophage JJ 947 950 CSF CSF NNP 951 955 plus plus CC 956 965 TNF-alpha TNF-alpha NNP 965 966 , , , 967 969 or or CC 970 973 PMA PMA NNP 974 975 ( ( ( 975 979 with with IN 980 982 or or CC 983 990 without without IN 991 994 the the DT 995 1002 calcium calcium NN 1003 1012 ionophore ionophore NN 1013 1022 ionomycin ionomycin NN 1022 1023 , , , 1024 1026 or or CC 1027 1036 TNF-alpha TNF-alpha NNP 1036 1037 ) ) ) 1037 1038 , , , 1039 1043 with with IN 1044 1053 different different JJ 1054 1061 stimuli stimulus NNS 1062 1071 mediating mediate VBG 1072 1081 different different JJ 1082 1089 aspects aspect NNS 1090 1092 of of IN 1093 1096 the the DT 1097 1104 process process NN 1104 1105 . . . 1106 1116 Phenotypic phenotypic JJ 1117 1119 DC DC NNP 1120 1135 characteristics characteristic NNS 1136 1138 of of IN 1139 1142 KG1 kg1 NN 1143 1157 dendritic-like dendritic-like JJ 1158 1163 cells cell NNS 1164 1171 include include VBP 1172 1182 morphology morphology NN 1183 1184 ( ( ( 1184 1191 loosely loosely RB 1192 1200 adherent adherent JJ 1201 1206 cells cell NNS 1207 1211 with with IN 1212 1216 long long JJ 1217 1224 neurite neurite NN 1225 1234 processes process NNS 1234 1235 ) ) ) 1235 1236 , , , 1237 1240 MHC MHC NNP 1241 1247 I+/MHC I+/MHC NNP 1248 1274 IIbright/CD83+/CD86+/CD14- IIbright/CD83+/CD86+/CD14- NNP 1275 1282 surface surface NN 1283 1285 Ag ag NN 1286 1296 expression expression NN 1296 1297 , , , 1298 1301 and and CC 1302 1306 RelB RelB NNP 1307 1310 and and CC 1311 1317 DC-CK1 dc-ck1 NN 1318 1322 gene gene NN 1323 1333 expression expression NN 1333 1334 . . . 1335 1345 Functional functional JJ 1346 1348 DC DC NNP 1349 1364 characteristics characteristic NNS 1365 1372 include include VBP 1373 1378 fluid fluid NN 1379 1384 phase phase NN 1385 1398 macromolecule macromolecule NN 1399 1405 uptake uptake NN 1406 1407 ( ( ( 1407 1419 FITC-dextran FITC-dextran NNP 1419 1420 ) ) ) 1421 1424 and and CC 1425 1435 activation activation NN 1436 1438 of of IN 1439 1446 resting rest VBG 1447 1448 T t NN 1449 1454 cells cell NNS 1454 1455 . . . 1456 1466 Comparison comparison NN 1467 1469 of of IN 1470 1473 KG1 kg1 NN 1474 1476 to to TO 1477 1480 the the DT 1481 1497 PMA-unresponsive pma-unresponsive JJ 1498 1505 subline subline NN 1506 1510 KG1a KG1a NNP 1511 1518 reveals reveal VBZ 1519 1530 differences difference NNS 1531 1533 in in IN 1534 1544 expression expression NN 1545 1547 of of IN 1548 1551 TNF TNF NNP 1552 1561 receptors receptor NNS 1562 1563 1 1 CD 1564 1567 and and CC 1568 1569 2 2 CD 1569 1570 ; ; : 1571 1574 PKC PKC NNP 1575 1583 isoforms isoform NNS 1584 1589 alpha alpha NN 1589 1590 , , , 1591 1595 beta beta NN 1596 1597 I i CD 1597 1598 , , , 1599 1603 beta beta NN 1604 1606 II ii CD 1606 1607 , , , 1608 1611 and and CC 1612 1614 mu mu NN 1614 1615 ; ; : 1616 1619 and and CC 1620 1624 RelB RelB NNP 1624 1625 , , , 1626 1636 suggesting suggest VBG 1637 1641 that that IN 1642 1647 these these DT 1648 1667 components/pathways components/pathway NNS 1668 1671 are be VBP 1672 1681 important important JJ 1682 1685 for for IN 1686 1688 DC DC NNP 1689 1704 differentiation differentiation NN 1704 1705 . . . 1706 1714 Together together RB 1714 1715 , , , 1716 1721 these these DT 1722 1730 findings finding NNS 1731 1742 demonstrate demonstrate VBP 1743 1747 that that IN 1748 1756 cytokine cytokine NN 1757 1759 or or CC 1760 1767 phorbol phorbol NN 1768 1773 ester ester NN 1774 1785 stimulation stimulation NN 1786 1788 of of IN 1789 1792 KG1 KG1 NNP 1793 1795 is be VBZ 1796 1797 a a DT 1798 1803 model model NN 1804 1806 of of IN 1807 1812 human human JJ 1813 1818 CD34+ cd34+ JJ 1819 1822 HPC HPC NNP 1823 1825 to to TO 1826 1828 DC DC NNP 1829 1844 differentiation differentiation NN 1845 1848 and and CC 1849 1856 suggest suggest VBP 1857 1861 that that IN 1862 1870 specific specific JJ 1871 1884 intracellular intracellular JJ 1885 1894 signaling signaling NN 1895 1903 pathways pathway NNS 1904 1911 mediate mediate VBP 1912 1920 specific specific JJ 1921 1927 events event NNS 1928 1930 in in IN 1931 1933 DC DC NNP 1934 1941 lineage lineage NN 1942 1952 commitment commitment NN 1952 1953 . . .