BRD4 directs hematopoietic stem cell development and modulates macrophage inflammatory responses

Name: Work Video:
Duration: 3 min 30 s
Anup Dey; Wenjing Yang; Anne Gégonne; Akira Nishiyama; Richard Pan; Ryoji Yagi; Alex Grinberg; Fred D. Finkelman; Karl Pfeifer; Jinfang Zhu; Dinah S. Singer; Jun Zhu; Keiko Ozato
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1020, 1060, 1106, 1157, 2776, 3627], 'author': [62, 108, 148, 194, 240, 288, 334, 356, 402, 450, 490, 536, 587, 633, 679, 719, 765, 811, 859, 905, 927, 973, 1021, 1061, 1107, 1158, 1319], 'Wenjing': [63, 65, 634, 636, 1163], 'Yang': [64, 66, 635, 637, 1707], 'The': [67, 495, 638, 1066, 1291, 2473, 2669, 3262, 3458, 3469], 'DNA': [68, 496, 639, 1067, 1206], 'Sequencing': [69, 497, 640, 1068, 1207], 'Computational': [71, 499, 642, 1070, 1209], 'Heart,': [74, 502, 645, 1073, 1212], 'Lung': [75, 503, 646, 1074, 1213], 'Blood': [77, 505, 648, 1076, 1215], 'Institute,': [78, 118, 460, 506, 649, 689, 1031, 1077, 1216, 1225], 'Anne': [109, 111, 680, 682, 1165], 'Gegonne': [110, 112, 681, 683], 'Experimental': [113, 455, 684, 1026, 4347], 'Immunology': [114, 456, 685, 1027, 1221], 'Branch,': [115, 457, 686, 1028, 1222], 'Cancer': [117, 459, 688, 1030, 1224], 'Akira': [149, 151, 720, 722, 1167], 'Nishiyama': [150, 152, 721, 723, 1604], 'Richard': [195, 197, 766, 768, 1169], 'Pan': [196, 198, 767, 769], 'Ryoji': [241, 243, 812, 814, 1171], 'Yagi': [242, 244, 813, 815], 'Laboratory': [245, 407, 816, 978], 'Immunology,': [247, 409, 818, 980, 1231, 1259, 1273], 'Allergy': [251, 413, 822, 984, 1235], 'Infectious': [253, 415, 824, 986, 1237], 'Diseases,': [254, 416, 825, 987, 1238], 'Institutes': [256, 418, 827, 989, 1240], 'Health,': [258, 420, 829, 991, 1242], 'Alex': [289, 291, 860, 862, 1173], 'Grinberg': [290, 292, 861, 863], 'Fred': [335, 338, 906, 909, 1175], 'D': [336, 339, 907, 910, 1176], 'Finkelman': [337, 340, 908, 911], 'Department': [341, 912, 1257, 1271], 'Pediatrics,': [343, 914, 1248], 'Cincinnati': [344, 915, 1249], "Children's": [345, 916, 1250], 'Hospital,': [346, 917, 1251], 'Cincinnati,': [347, 918, 1252], 'OH,': [348, 919, 1253], 'Karl': [357, 359, 928, 930, 1178], 'Pfeifer': [358, 360, 929, 931], 'Jinfang': [403, 405, 974, 976, 1180], 'Zhu': [404, 406, 492, 494, 975, 977, 1063, 1065], 'Dinah': [451, 453, 1022, 1024, 1182], 'Singer': [452, 454, 1023, 1025], 'Jun': [491, 493, 1062, 1064, 1184], 'Keiko': [537, 541, 1108, 1112, 1187], 'Ozato': [538, 542, 1109, 1113, 1188], 'Corresponding': [539, 1110, 2632], 'Author': [540, 1111, 1159], '[email': [543, 1114, 1289], 'protected]': [544, 1115, 1290], 'orcid.org/0000-0001-5866-3075': [545, 1116], 'Information': [1160], 'Dey1,': [1162], 'Yang2,': [1164], 'Gegonne3,': [1166], 'Nishiyama1,6,': [1168], 'Pan1,': [1170], 'Yagi4,7,': [1172], 'Grinberg1,': [1174], 'Finkelman5,': [1177], 'Pfeifer1,': [1179], 'Zhu4,': [1181], 'Singer3,': [1183], 'Zhu2': [1185], '*,1': [1189], '1Division': [1190], '2The': [1205], '3Experimental': [1220], '4Laboratory': [1229], '5Department': [1246], '6Present': [1255], 'address:': [1256, 1270], 'Graduate': [1260, 1274], 'School': [1261, 1275], 'Medicine,': [1263, 1277], 'Yokohama': [1264], 'City': [1265], 'University,': [1266, 1279], 'Yokohama,': [1267], 'Japan': [1268, 1281], '7Present': [1269], 'Chiba': [1278], 'Chiba,': [1280], '*Corresponding': [1282], 'author.': [1283], 'Tel:': [1284], '+1': [1285], '301496': [1286], '9184;': [1287], 'E-mail:': [1288], 'EMBO': [1292], 'Journal': [1293], '(2019)38:e100293https://doi.org/10.15252/embj.2018100293': [1294], 'PDFDownload': [1295], 'PDF': [1296], 'text': [1299], 'main': [1301], 'figures.': [1302], 'Peer': [1303], 'ReviewDownload': [1304], 'a': [1305, 1336, 1358, 1473, 1565, 1627, 1833, 2021, 2073, 2084, 2125, 2266, 2285, 2305, 2492, 2679, 2929, 3113, 3245, 3394, 3508, 3896, 3975, 4251], 'summary': [1306], 'editorial': [1309, 1313], 'decision': [1310, 1314], 'including': [1312, 1722, 1749, 1776, 1848, 4131], 'letters,': [1315], 'reviewer': [1316], 'comments': [1317], 'feedback.': [1322], 'ToolsAdd': [1323], 'favoritesDownload': [1325], 'CitationsTrack': [1326], 'CitationsPermissions': [1327], 'ShareFacebookTwitterLinked': [1328], 'InMendeleyWechatReddit': [1329], 'Figures': [1330], '&': [1331, 1583, 1907], 'Info': [1332], 'Abstract': [1333], 'BET': [1337, 1491, 1560, 1571, 1743, 1894, 2097, 3784, 3912, 3917, 4205, 4237, 4291, 4325], 'family': [1338, 1492, 1744], 'protein': [1339, 1493, 1568, 2176, 2574], 'that': [1340, 1385, 1413, 1453, 1807, 1932, 1962, 2004, 2027, 2048, 2061, 2396, 2429, 2995, 3038, 3181, 3301, 3881, 3908, 4030, 4065, 4235, 4302, 4321], 'binds': [1341, 1687], 'acetylated': [1342, 1597, 1676], 'histones': [1343, 1598], 'regulates': [1345, 3088], 'transcription.': [1346, 4202], 'BET/BRD4': [1347], 'inhibitors': [1348, 1739, 1766, 1809, 1895, 3785, 3918, 4326], 'block': [1349], 'blood': [1350, 1774, 1902, 2249], 'cancer': [1351, 1636], 'growth': [1352, 1769], 'inflammation': [1354, 1372, 1843, 1905, 2019, 3799, 4272], 'serve': [1356], 'as': [1357, 1446, 3226, 3276, 3637, 3639, 3665, 3764, 3967, 4293], 'new': [1359, 1897], 'therapeutic': [1360, 1898, 2094], 'strategy.': [1361], 'However,': [1362], 'biological': [1364], 'role': [1365, 1475, 1751, 1955, 1973, 2086, 2185, 2921, 3944], 'normal': [1369, 1507, 1634, 1936], 'hematopoiesis': [1370, 1508, 1997, 2785], 'not': [1374, 1441, 1939, 3050, 3075, 3123, 3267, 3885], 'fully': [1375, 1940], 'understood.': [1376], 'Analysis': [1377, 3143], 'Brd4': [1379, 1548, 2067, 2101, 2110, 2117, 2131, 2136, 2151, 2157, 2172, 2193, 2219, 2393, 2430, 2460, 2478, 2517, 2533, 2564, 2591, 2598, 2782, 2801, 2906, 2923, 2950, 2963, 3007, 3039, 3125, 3156, 3302, 3315, 3332, 3388, 3400, 3427, 3489, 3631, 3729, 3774, 3819, 3836, 3882, 3999, 4020, 4048, 4110, 4222, 4246, 4261, 4288, 4322, 4337, 4356, 4374, 4386], 'conditional': [1380, 1485, 2111], 'knockout': [1381, 1487, 2112], '(KO)': [1382, 2113, 4406], 'mice': [1383, 2138, 2196, 2361, 2395, 2432, 2519, 2540, 2546, 2601, 2794, 2836, 2880, 2953, 3099, 3179, 3351, 3390, 3414, 3429, 3456, 4359], 'showed': [1384, 1412, 1806, 2284, 2994, 3112, 3180, 4029, 4176], 'required': [1388, 1442, 1513, 1995, 2444], 'expansion': [1393], 'progenitor': [1395, 2321, 2453, 2650, 2712], 'development.': [1396, 2454, 3893], 'Nevertheless,': [1397, 3278], 'played': [1399], 'limited': [1400, 1416, 4168], 'roles': [1401], 'response': [1407], 'LPS.': [1409, 4373], 'ChIP-seq': [1410, 2024], 'analysis': [1411, 2025, 2279, 2300, 2788, 2804, 2843, 3200, 3248, 3480, 3560, 3651, 3724, 3737, 3952, 4122], 'despite': [1414], 'its': [1415, 1503, 1723, 1750, 1972, 2558], 'importance,': [1417], 'broadly': [1419, 1533, 1587, 2029, 3993], 'occupied': [1420], 'genome': [1423, 1593], 'participated': [1425], 'super-enhancer': [1427], '(SE)': [1428], 'formation.': [1429], 'Although': [1430], 'critical': [1433], 'SE': [1435], 'formation': [1436], 'cancer,': [1438], 'was': [1440, 2064, 2119, 2226, 2593, 2682, 2746, 2789, 2888, 3249, 3594, 4375], 'SEs,': [1445, 1812], 'KO': [1447, 2068, 2152, 2220, 2240, 2294, 2347, 2360, 2384, 2394, 2423, 2431, 2565, 2630, 3002, 3008, 3096, 3126, 3157, 3190, 3233, 3274, 3350, 3373, 3389, 3401, 3413, 3428, 3455, 3490, 3551, 3572, 3730, 3745, 3851, 4021, 4049, 4073, 4111, 4119, 4162, 4170, 4223, 4247, 4289, 4323, 4417, 4440, 4458], 'macrophages': [1448, 2050, 2915, 2935, 2942, 2998, 3009, 3022, 3056, 3158, 3163, 3176, 3191, 3254, 3293, 3340, 3552, 3573, 3649, 3654, 3679, 3689, 3747, 3783, 3823, 3844, 3869, 3927, 3955, 4074, 4171, 4346, 4418], 'created': [1449], 'alternate,': [1450], 'BRD4-less': [1451], 'SEs': [1452, 1663, 2034, 2052], 'compensated': [1454], 'loss.': [1456], 'This': [1457], 'additional': [1459, 2091], 'mechanisms': [1460, 1718], 'led': [1461, 3877], 'retention': [1464], 'macrophages.': [1469, 1547, 2037, 2970, 4120, 4163, 4352, 4459], 'Our': [1470], 'results': [1471, 3036, 3299, 3864, 3876, 4319], 'illustrate': [1472], 'context-dependent': [1474, 2085], 'plasticity': [1479], 'epigenetic': [1481], 'regulation.': [1482], 'Synopsis': [1483], 'New': [1484], 'mouse': [1486, 1519, 2471], 'models': [1488], 'BRD4,': [1494], 'involved': [1495, 3183], 'transcriptional': [1497], 'control': [1498], 'cancers,': [1501, 1772, 1775], 'reveal': [1502], 'differential': [1504], 'requirement': [1505], 'inflammation.': [1510, 2933], 'proliferation': [1517, 2358, 2911, 3065, 3103, 3131, 3269, 3336], 'cells.': [1522, 2439], 'dispensable': [1525, 2016, 4196], 'differentiation': [1528, 3168], 'response.': [1531], 'occupies': [1534, 1588, 2030], 'genic': [1535, 1689, 2031], 'intergenic': [1537], 'regions': [1538, 1590, 2032], 'transcribed': [1540], 'genes': [1541, 3182, 3203, 3283, 3504, 3528, 3549, 3569, 3640, 3662, 3674, 3687, 3712, 3726, 3739, 3761, 3924, 3966, 4011, 4067, 4094, 4106, 4115, 4158, 4258, 4265, 4306], 'both': [1543, 3715, 4079], 'unstimulated': [1544], 'LPS-stimulated': [1546, 4157, 4328], 'deletion': [1549, 2102, 2158, 2458, 2469, 2504, 2783, 2907, 2964, 3040, 3303, 3316, 3330, 3632, 3775, 3820, 3837, 3883, 4338], 'associated': [1551], 'with': [1552, 1669, 2124, 2141, 2368, 2520, 2642, 2814, 2978, 3012, 3256, 3507, 3518, 3656, 3691, 3749, 3867, 3916, 3969, 3974, 4012, 4166, 4372], 'increased': [1553], 'NF-κB': [1554, 2062], 'occupancy': [1555], 'increase': [1557, 3115], 'other': [1559, 1717, 4204], 'proteins.': [1561], 'Introduction': [1562], 'double': [1566], 'bromodomain': [1567], 'family,': [1572], 'expressed': [1573, 3282, 3503, 3527, 3545, 3661, 3673, 3741, 3760, 3965, 4240], 'ubiquitously': [1574], 'at': [1575, 1678, 2243, 3756, 3979, 4241], 'high': [1576], 'levels': [1577, 4244, 4413], '(Dey': [1578, 1599], 'et': [1579, 1600, 1605, 1609, 1613, 1617, 1621, 1647, 1651, 1656, 1660, 1682, 1704, 1708, 1712, 1727, 1731, 1758, 1762, 1782, 1786, 1790, 1794, 1799, 1818, 1822, 1827, 1858, 1862, 1866, 1870, 1874, 1879, 1883, 1887, 1911, 1915, 1919, 1943, 2198, 2331, 3032, 3067, 3105, 3801, 3805, 3810, 3929, 3933, 3938, 3988, 4226, 4297], 'al,': [1580, 1601, 1606, 1610, 1614, 1618, 1622, 1648, 1652, 1657, 1661, 1683, 1705, 1709, 1713, 1728, 1732, 1759, 1763, 1783, 1787, 1791, 1795, 1800, 1819, 1823, 1828, 1859, 1863, 1867, 1871, 1875, 1880, 1884, 1888, 1912, 1916, 1920, 1944, 2199, 2332, 3033, 3068, 3106, 3802, 3806, 3811, 3930, 3934, 3939, 3989, 4227, 4298], '2000;': [1581], 'Wu': [1582], 'Ghosh,': [1584], '2003).': [1585], 'various': [1589, 1771], 'binding': [1595, 2063], '2003,': [1602], '2009;': [1603], '2006;': [1607], 'Zhang': [1608], '2012;': [1611, 1864, 1909], 'Hnisz': [1612], '2013;': [1615, 1619, 1649, 1653, 1658, 1788, 1820, 1868, 1872, 1876, 3807, 3935], 'Lovén': [1616, 1650, 1785], 'Kanno': [1620, 1711], '2014).': [1623, 1714, 3812, 3940], 'also': [1626, 1686, 1841, 2165, 3250, 4175], 'prominent': [1628], 'component': [1629], 'super-enhancers': [1631], '(SEs)': [1632], 'cells': [1637, 1937, 1981, 2212, 2283, 2317, 2367, 2408, 2566, 2596, 2640, 2721, 2811, 2828, 2850, 2867, 2875, 2975, 3346, 3369, 3398, 3408, 3444, 3461, 3497, 4024, 4078, 4097, 4224, 4354], 'helps': [1639], 'define': [1640], 'type': [1642], 'lineage': [1644, 2407], 'specificity': [1645], '(Hnisz': [1646, 1681], 'Whyte': [1654], 'Warren': [1655], 'Pelish': [1659, 1793, 1821], '2015).': [1662], 'are': [1664, 1938, 2177, 2433, 2695, 2730, 2861, 2928, 2943, 3535, 3553, 4034, 4207, 4239], 'large': [1665, 3013, 3114], 'regulatory': [1666, 2056], 'DNAs,': [1667], 'enriched': [1668], 'RNA': [1670], 'polymerase': [1671], 'II': [1672], '(PoI': [1673], 'II)': [1674], 'H3': [1677], 'K27': [1679], '(H3K27ac)': [1680], '2013).': [1684, 3070, 3107, 4228], 'regions,': [1690], 'most': [1691], 'strongly': [1692], 'at/near': [1693], 'transcription': [1695, 1701, 4182, 4329], 'start': [1696], 'site': [1697], '(TSS),': [1698], 'thereby': [1699], 'facilitating': [1700], 'elongation': [1702], '(Jang': [1703], '2005;': [1706, 1710], 'employs': [1716], 'promote': [1720], 'transcription,': [1721, 3995], 'kinase': [1724], 'activity': [1725], '(Devaiah': [1726], '2016;': [1729, 1917], 'Winter': [1730], '2017).': [1733, 1889, 1921], 'Recent': [1734], 'small': [1737], 'molecule': [1738], 'selective': [1740], 'greatly': [1745, 2381], 'advanced': [1746], 'research,': [1748], 'cancers': [1753, 1903], 'diseases': [1756, 1856], '(Filippakopoulos': [1757], '2010;': [1760, 1860, 3803, 3931], 'Nicodeme': [1761], '2010).': [1764, 3034], 'These': [1765, 1830, 1839, 3035, 3298, 3875, 4318], 'potently': [1767], 'inhibit': [1768, 1842, 4327], 'particularly': [1773, 3793], 'leukemia,': [1777], 'lymphoma,': [1778], 'myeloma': [1780], '(Zuber': [1781], '2011;': [1784], 'Ceribelli': [1789, 1910], '2014;': [1792, 1881, 1885, 1913], '2015;': [1796, 1824], 'Bhagwat': [1797, 1825], 'Anand': [1798, 1826, 1865], '2016).': [1801, 1829, 1945], 'Some': [1802], 'these': [1804, 1891, 1926, 2417, 4236], 'studies': [1805], 'disrupt': [1810], 'BRD4-bound': [1811], 'resulting': [1813, 2508], 'oncogene': [1815], 'downregulation': [1816], '(Lovén': [1817], 'findings': [1831], 'offered': [1832], 'possible': [1834], 'mechanism': [1835, 2075], 'inhibitor': [1837, 4292], 'action.': [1838], 'drugs': [1840, 1927], 'ameliorate': [1845], 'related': [1846, 3209], 'diseases,': [1847], 'LPS-induced': [1849, 3778, 3798, 3923, 4010, 4181, 4201, 4341], 'sepsis,': [1850], 'EAE-based': [1851], 'neuroinflammation,': [1852], 'diabetes,': [1853], 'cardiovascular': [1855], '(Nicodeme': [1857, 3800, 3928, 4296], 'Bandukwala': [1861], 'Belkina': [1869, 3804, 3932], 'Mele': [1873], 'Brown': [1877, 3808, 3936], 'Jonathan': [1878, 3809, 3937], 'Fu': [1882], 'Duan': [1886], 'With': [1890], 'encouraging': [1892], 'effects,': [1893], 'offer': [1896], 'possibilities,': [1899], 'mainly': [1900], '(Belkina': [1906, 4225], 'Denis,': [1908], 'Berthon': [1914], 'Ghosh': [1918], 'A': [1922, 2464, 2704], 'potential': [1923], 'problem': [1924], 'using': [1925, 3826], 'therapy,': [1929], 'however,': [1930, 3073], 'effects': [1934], 'on': [1935, 1953, 2684, 3821, 4398], 'evaluated': [1941], '(Andrieu': [1942], 'Particularly': [1946], 'problematic': [1947], 'dearth': [1950], 'knowledge': [1952], 'cells,': [1960, 2312, 2323, 2339, 2673, 4248], 'although': [1963, 3047], 'essential': [1966], 'early': [1968, 2189, 2648, 2711], 'embryogenesis': [1969], 'mice,': [1971, 2114, 3121, 3127], 'function': [1978, 2012], 'remained': [1983], 'elusive.': [1984], 'It': [1985, 3904], 'unknown': [1987], 'whether': [1988, 3086, 3998], 'what': [1991], 'extent': [1992], 'responses.': [2000, 2079], 'Here,': [2001], 'we': [2002, 2059, 2191, 2389, 2957, 3091, 3949, 3996, 4214, 4283], 'show': [2003, 2060, 3300, 4064, 4269], 'indispensable': [2007], 'HSCs,': [2014, 2340, 2676], 'but': [2015, 3122], 'significant': [2022], 'extent.': [2023], 'revealed': [2026, 3204, 4234], 'quiescent': [2036], 'Further,': [2038], 'LPS': [2039, 3894, 3958, 4086, 4090], 'stimulation': [2040, 3324, 3646], 'dramatically': [2041], 'altered': [2042], 'distribution': [2044], 'patterns.': [2045], 'We': [2046, 2916, 3813, 3962, 4005], 'demonstrate': [2047], 'Brd4KO': [2049, 2251], 'retain': [2051, 2077], 'forming': [2054], 'alternative': [2055], 'network.': [2057], 'Lastly,': [2058], 'elevated': [2065], 'macrophages,': [2069, 2925, 2967, 3046, 3234, 3275, 3792, 4112], 'which': [2070, 2313, 3237], 'may': [2071], 'provide': [2072], 'compensatory': [2074, 4252], 'Together,': [2080, 2440, 4153], 'our': [2081], 'highlights': [2083], 'offers': [2090], 'clues': [2092], 'use': [2095], 'inhibitors.': [2098], 'Results': [2099, 3108, 4028], 'Vav-Cre-based': [2100, 2800], 'blocks': [2103, 2461], 'To': [2108, 2182, 3084, 3941], 'construct': [2109], 'endogenous': [2116], 'locus': [2118, 2479], 'replaced,': [2120], 'homologous': [2122], 'recombination,': [2123], 'vector': [2126, 2482], 'containing': [2127], 'loxP': [2128], 'sites': [2129, 2489], 'flanking': [2130], 'exon': [2132, 2484, 2506], '3': [2133, 2485, 2507, 2734], '(Fig': [2134, 2161, 2213, 2275, 2296, 2362, 2386, 2409, 3027, 3159, 3192, 3215, 3242, 3260, 3294, 3325, 3828, 3860, 3873, 4151, 4183], '1A).': [2135], 'fl/fl': [2137, 2194, 2261, 2518, 2534, 2599, 2951, 4357], 'were': [2139, 2253, 2343, 2379, 2419, 2547, 2567, 2656, 2976, 2999, 3010, 3023, 3187, 3230, 3238, 3284, 3493, 3505, 3663, 3682, 3762, 3845, 3865, 4068, 4107, 4116, 4159, 4309, 4360], 'crossed': [2140], 'those': [2142, 3536, 3968], 'carrying': [2143, 2414], 'Vav-Cre,': [2144], 'LysM-Cre,': [2145], 'or': [2146, 2375, 2405, 2523, 2557, 2604, 3273, 3488, 3914, 4404, 4452], 'ERT2-Cre': [2147, 2160, 2521, 3827, 4358], 'generate': [2149], 'cell-type-specific': [2150], 'mice.': [2153, 2631, 3491, 3576], 'Examples': [2154], 'successful': [2156], '1B': [2162, 3840, 4382], 'see': [2164], 'Appendix': [2166, 2235, 3218, 3562], 'Fig': [2167, 2180, 2236, 2328, 2955, 2988, 2992, 3110, 3137, 3219, 3563, 3667, 3696, 3839, 4026, 4058, 4101, 4191, 4232, 4316, 4381], 'S1A)': [2168], 'depletion': [2170, 2207, 2592], 'mRNA': [2173, 2570], 'shown': [2178, 3554, 3907, 4208, 4310], '1C.': [2181], 'study': [2183, 2919], 'hematopoiesis,': [2190], 'tested': [2192, 2568, 3789], 'Vav-Cre': [2195, 2457, 2600], '(Georgiades': [2197], '2002).': [2200], 'qRT–PCR': [2201, 2577, 2607, 3241, 3565, 3680, 4121, 4188], 'immunoblot': [2203, 2579, 2609], 'experiments': [2204, 2587, 2619, 3476, 3584, 4441], 'confirmed': [2205, 2548, 3151, 4127], 'thorough': [2206], 'resultant': [2211], '1D).': [2214], 'Strikingly,': [2215], 'number': [2217, 2336, 2670, 2825, 2864, 3710, 4421], 'offspring': [2221], 'obtained': [2222], 'from': [2223, 2256, 2536, 2597, 2627, 2796, 2829, 2834, 2838, 2868, 2876, 2878, 2882, 2937, 2945, 3079, 3177, 3347, 3370, 3399, 3409, 3451, 3495, 3574, 3848, 4355, 4401, 4426, 4449], 'multiple': [2224], 'crosses': [2225], 'far': [2227], 'fewer': [2228, 3000], 'than': [2229, 3004, 4070], 'expected': [2230], '(3': [2231], 'out': [2232], '204,': [2234], 'S1B).': [2237], 'Majority': [2238], 'embryos': [2241, 2252, 2259, 2295, 2348, 2385, 2626, 2700, 2736], 'died': [2242], 'birth,': [2244], 'presumably': [2245], 'due': [2246], 'defective': [2248, 3130], 'supply.': [2250], 'readily': [2254], 'distinguished': [2255], 'wild-type': [2257], '(WT)': [2258, 2560, 4403], '(Brd4': [2260], 'and/or': [2262], 'Brd4+/+,': [2263], 'Vav-Cre)': [2264], 'reduced': [2267, 2382, 2421, 3152], 'size': [2268], 'pale': [2270], 'hue': [2271], 'fetal': [2273, 2281, 2398, 2638, 2680], 'liver': [2274, 2282, 2603, 2639, 2681], '1E).': [2276], 'Flow': [2277, 2786, 2841, 3341, 3403, 3432, 4388], 'cytometry': [2278, 2787, 3342, 3404, 3433, 4389], 'marked': [2286, 3205], 'reduction': [2287, 2307, 3395], 'Lin−': [2289, 2637], 'Sca+cKit+': [2290], '(LSK)': [2291, 2652], 'population': [2292, 2303, 2651, 3135, 4396], '1F,': [2297, 2363], 'left).': [2298], 'Further': [2299], 'LSK': [2302, 2338, 2654], 'found': [2304, 4301], 'severe': [2306], 'Flt3lo': [2309], 'Flt3hI': [2311], 'represent': [2314, 2582, 2614, 2822, 3380, 3419, 3471, 3578, 4432], '(HSCs)': [2318], 'multipotent': [2320], '(MPP)': [2322], 'respectively': [2324], '(a': [2325], 'diagram': [2326, 3707, 3832, 4099], '1G;': [2329], 'Adolfsson': [2330], '2005).': [2333], 'Accordingly,': [2334], 'total': [2335, 2672, 2972, 3855], 'MPPs': [2342, 2667], 'strikingly': [2344], 'lower': [2345], 'relative': [2349], 'WT,': [2351], 'pointing': [2352], 'lack': [2355], 'HSC': [2357, 2462], 'right': [2364, 3141], 'panels).': [2365, 3142], 'Consequently,': [2366], 'myeloid': [2369, 2404, 2725, 2827], 'lymphoid': [2371, 2406, 2727], 'markers': [2373, 2415], '(GR-1': [2374], 'B220': [2376], 'vs.': [2377, 3530, 3702], 'CD11b)': [2378], 'likewise': [2380], '1H).': [2387], 'Additionally,': [2388], 'examined': [2390, 2959, 3101, 3815, 4215], 'two': [2391, 2792, 2835, 2879, 4032], 'adult': [2392], 'escaped': [2397, 2795, 2837, 2881], 'death': [2399, 2798], 'presence': [2402, 2551, 4364], 'EV1A': [2410], 'B).': [2412], 'Cells': [2413], 'lineages': [2418], 'drastically': [2420], 'bone': [2424, 2806, 2830, 2845, 2869, 2946], 'marrow': [2425, 2807, 2831, 2846, 2870, 2947], 'spleen,': [2427], 'indicating': [2428], 'largely': [2434], 'devoid': [2435], 'functional': [2437], 'immune': [2438], 'critically': [2443], 'generation': [2447], 'embryonic': [2449, 2688, 2797, 2839, 2883], 'HSCs': [2450, 2665, 2948], 'subsequent': [2452], 'Figure': [2455, 2778, 3327, 3629, 4335], '1.': [2456], 'schematic': [2465, 2705], 'representation': [2466], 'targeted': [2468], 'Brd4.': [2472], 'exon–intron': [2474], 'organization': [2475], '(top).': [2480, 2541], 'Targeting': [2481], 'contained': [2483], 'flanked': [2486, 2496], 'LoxP': [2488], '(green)': [2490], 'neomycin': [2493], 'resistance': [2494], 'gene': [2495, 3483, 3556, 3635, 3779, 4003, 4212, 4342], 'FRT': [2498], '(white).': [2499], 'Cre-mediated': [2500], 'recombination': [2501], 'should': [2502], 'cause': [2503, 3076], 'loss': [2510], 'expression': [2513, 3150, 3441, 3484, 3780, 3920, 4216, 4343, 4412], '(bottom).': [2514, 2561], 'Genotyping': [2515], '(Cre)': [2522, 2556], 'without': [2524], 'ERT2': [2525, 2553], '-Cre': [2526, 2554], '(+/+).': [2527], 'Tamoxifen': [2528], 'treatment': [2529, 3265, 3915, 4091, 4379], 'deleted': [2530, 4376], '2.2': [2531], 'kb': [2532], 'fragment': [2535], 'Cre/+': [2537], 'Cre/Cre': [2539, 2543], 'Cre/+,': [2542], '+/+': [2545], 'band': [2555], 'absence': [2559], 'WT': [2562, 2628, 3005, 3021, 3098, 3120, 3272, 3348, 3371, 3385, 3411, 3424, 3453, 3487, 3743, 3849, 4023, 4077, 4096, 4415, 4437, 4456], '(left)': [2571, 2808, 2847], '(right)': [2575, 2812, 2821, 2851, 2860, 3379, 3418], 'assays.': [2580], 'Values': [2581, 2613, 2694, 2729, 3577, 4431], 'average': [2584, 2616, 2697, 2732, 2824, 2863, 3382, 3421, 3473, 3580, 4434], 'three': [2586, 2618, 3475, 3582], '±': [2588, 2620, 2701, 2737, 3391, 3430, 3477, 3585, 4442], 'SD.': [2589, 2621, 2738, 3392, 3431, 3478, 3586, 4443], 'Vav-Cre-mediated': [2590], 'verified': [2594, 3239], '(fetal': [2602], 'spleen)': [2605], '(left': [2610, 4060], 'right).': [2612], 'Photographic': [2622], 'images': [2623], 'E14.5': [2625], 'flow': [2633, 2716], 'cytometric': [2634, 2717, 2842], 'profile': [2635, 2718, 3359], 'stained': [2641, 2722, 2813, 2852, 2977, 3352], 'cKit': [2643], 'Sca-1': [2645], 'antibodies': [2646], 'examining': [2647], '(left).': [2653, 3357, 3415, 3457, 4408], 'populations': [2655, 3375], 'further': [2657], 'divided': [2658], 'Flt3': [2661], 'marker': [2662], 'detect': [2664], '(middle).': [2668, 3376, 4419], 'e.g.,': [2674], 'LSKs,': [2675], 'MPPs,': [2677], 'estimated': [2683], 'indicated': [2685, 2754, 2896, 3602], 'days': [2686, 4369], '(E13.5,': [2690], 'E14.5,': [2691], 'E17.5).': [2693], '3–5': [2699], 'SD': [2702], '(right).': [2703, 3468], 'pathways.': [2714], 'Representative': [2715, 3547], 'CD71−': [2720], 'markers.': [2728], 'E17.5': [2735], 'Data': [2739, 2885, 2990, 3587], 'information:': [2740, 2886, 3588], 'Statistical': [2741, 3589], 'significance': [2742, 3590, 3976], 'all': [2744, 3592], 'figures': [2745, 3593], 'determined': [2747, 2889, 3595], 'two-tailed': [2749, 2891, 3597], 'unpaired': [2750, 2892, 3598], 't-test': [2751, 2893, 3599], 'by:': [2755, 2897, 3603], '*P': [2756, 3604], '<': [2757, 2760, 2763, 2899, 3521, 3605, 3608, 3611, 3614, 3981], '0.05,': [2758, 3606], '**P': [2759, 2898, 3607], '0.01,': [2761, 3609], '***P': [2762, 3610], '0.001,': [2764, 3612], 'NS:': [2765, 3616], 'no': [2766, 3617], 'significance.': [2767, 3618], 'Download': [2768, 2770, 2901, 2903, 3619, 3621, 3770, 3772], 'figure': [2769, 2902, 3620, 3771], 'PowerPoint': [2771, 2904, 3622, 3773], 'Click': [2772, 3623], 'here': [2773, 3624, 4308], 'expand': [2775, 3626], 'figure.': [2777, 3628], 'EV1.': [2779], 'Effect': [2780], 'performed': [2790, 3251, 3683, 3950], '8-week-old': [2793], 'KO.': [2802], 'FACS': [2803, 3358, 3858], 'spleen': [2810, 2833, 2849, 2877], 'CD11b': [2815], 'Gr1': [2817], 'antibodies.': [2818], 'Bar': [2819, 2858], 'graphs': [2820, 2859], 'death.': [2840, 2884], 'CD19/IgM': [2854], 'B220/H57,': [2856], 'respectively.': [2857], 'B': [2866, 2872], 'T': [2874], 'Significance': [2887], '0.01.': [2900], 'LysM-Cre-based': [2905], 'compromises': [2908, 3041], 'resident': [2913, 2969, 3044, 3162, 3338], 'peritoneal': [2914, 2966, 2973, 3045, 3175, 3253, 3339, 3345, 3407, 3443, 3496, 3648, 3653, 3746], 'sought': [2917], 'because': [2926], 'they': [2927], 'primary': [2930], 'source': [2931], 'Resident': [2934], 'originate': [2936], 'yolk-sac': [2938], 'progenitors,': [2939], 'while': [2940, 3309], 'circulating': [2941], 'derived': [2944], 'Using': [2949], 'LysM-Cre': [2952, 3329, 3872, 4174], '(Appendix': [2954, 2987, 4025, 4315], 'S2A),': [2956], 'first': [2958], 'effect': [2961, 3817, 4046, 4286], 'representative': [2968, 3568, 3685], 'First,': [2971], 'cavity': [2974], 'CD19-FITC,': [2979], 'CD11b-PE,': [2980], 'F4/80-APC': [2982], 'depict': [2984], 'compensation': [2985], 'controls': [2986], 'S2B).': [2989], '2A': [2993, 3138], 'CD19−': [2996, 3361, 3449], 'F4/80+': [2997, 3133, 3366, 3397, 3447, 4394], 'peritoneum': [3003], 'counterpart.': [3006], 'constituted': [3011], 'numbers': [3014, 3118, 3378, 3417, 3459, 3470], 'F4/80low': [3016], 'CD11blow': [3018], 'population,': [3019], 'whereas': [3020, 4113], 'predominantly': [3024], 'F4/80high,': [3025], 'CD11bhigh': [3026], '2A,': [3028], 'middle': [3029, 4062], 'panel;': [3030], 'Ghosn': [3031], 'indicate': [3037, 3525, 4320], 'it': [3048], 'does': [3049, 3074, 3884], 'totally': [3051], 'abolish': [3052], 'process.': [3054], 'Peritoneal': [3055], 'respond': [3057], 'Th2': [3060], 'cytokine': [3061], 'IL-4': [3062, 3071, 3257, 3643, 3657, 3692, 3721, 3734], 'undergo': [3064], '(Jenkins': [3066, 3104], '2011,': [3069], 'stimulation,': [3072], 'recruitment': [3078], 'elsewhere': [3080], 'body.': [3083], 'test': [3085], 'proliferation,': [3090], 'injected': [3092], 'IL-4C': [3093], 'complexes': [3094], 'into': [3095], '2B': [3111], 'indicative': [3128, 4249], '(compare': [3132], 'B,': [3140], 'BrdU': [3145, 3436], 'incorporation,': [3146, 3437], 'Ki-67,': [3147, 3438, 3465], 'ARG1': [3149, 3440, 3467], 'division': [3154, 3186, 3212], '2C).': [3160], 'Thus,': [3161, 4193], 'require': [3164], 'full': [3167], 'IL-4-induced': [3170], 'proliferation.': [3171], 'Microarray': [3172, 3479, 3650, 3736], 'analyses': [3173, 3681], 'IL-4C-treated': [3178, 3452, 3486, 3575], 'downregulated': [3188, 3202, 3231, 3548, 3570, 3713, 3727, 4069, 4108, 4160, 4311], '2D': [3193, 3767], 'E).': [3195, 3297], 'Hierarchical': [3196, 3541, 3669], 'clustering': [3197, 3542, 3670], 'GO': [3199, 3559, 3723, 4255], 'enrichment': [3206, 4270], 'categories': [3208], 'mitosis': [3214], '2E': [3216, 3697], 'S2C).': [3220], 'In': [3221, 4164, 4254], 'addition,': [3222], 'M2-specific': [3223], 'genes,': [3224], 'such': [3225], 'Arg1': [3227], 'Chil3/Ym1,': [3229], 'some': [3235], '2F).': [3243], 'As': [3244], 'comparison,': [3246], 'microarray': [3247], 'treated': [3255, 3655, 3690, 3748, 4371], 'ex': [3258, 3263, 3290, 3658, 3677, 3693, 3703, 3719, 3732, 3751], 'vivo': [3259, 3264, 3288, 3291, 3678, 3701, 3704, 3717, 3720, 3733, 3752], 'EV2A–C).': [3261], 'did': [3266], 'induce': [3268], 'either': [3271], 'anticipated.': [3277], '30-40%': [3279], 'differentially': [3281, 3526, 3544, 3672, 3740, 3964], 'shared': [3285], 'IL-4-treated': [3292, 3676], 'EV2D': [3295], 'obliterates': [3304], "macrophage's": [3305], 'ability': [3306], 'proliferate,': [3308], 'retaining': [3310], 'many': [3311], 'macrophage-specific': [3312], 'traits.': [3313], 'Similarly,': [3314], 'partially': [3317, 3776, 4339], 'impaired': [3318], 'typical': [3319], 'M1': [3320], 'upon': [3322], 'IFN-γ': [3323, 3645, 3750], 'EV2F).': [3326], '2.': [3328], 'impairs': [3333], 'profiles': [3343, 3405, 3434, 3859, 4390], 'CD19': [3354], 'F4/80': [3356, 4411], 'subset': [3362], 'showing': [3363, 3708, 3853], 'CD11b+': [3364, 4392], 'subsets': [3367], 'Cell': [3377, 3416], 'four': [3384, 3387, 3423, 3426], 'Note': [3393], 'peritoneum.': [3402], 'IL-4C-injected': [3410], '(gated': [3445], 'macrophages)': [3450], 'positive': [3462], 'BrdU,': [3464], 'Macrophages': [3492], 'isolated': [3494], 'MACS': [3500], 'system.': [3501], 'Differentially': [3502, 3660, 3759], 'identified': [3506, 3664, 3763, 4307], 'cutoff': [3509, 3539], 'line': [3510], 'log2': [3512], 'fold': [3513, 3972], 'change': [3514, 3973], '>': [3515, 3970, 4198, 4427], '2': [3516, 3971], 'difference': [3517], 'P-value': [3519], '0.05.': [3522], 'Red': [3523], 'dots': [3524, 3534], '(KO': [3529], 'WT),': [3531], 'gray': [3533], 'below': [3537], 'line.': [3540], 'genes.': [3546], 'symbols.': [3557], 'See': [3558, 3695], 'S2C.': [3564], 'confirmation': [3566, 3834, 4189], 'independent': [3583, 4429], '****P': [3613], '0.0001,': [3615], 'EV2.': [3630], 'affected': [3633], 'cell-division-related': [3634], 'activities': [3636], 'well': [3638, 4035], 'responsive': [3641], 'vivo.': [3659, 3694], '2D.': [3668], 'M2': [3686], 'compare': [3699], 'treatment.': [3705, 3735], 'Venn': [3706], 'treatments.': [3722], 'after': [3731, 4085], '4': [3754, 3960], 'h': [3755], '100': [3757], 'U/ml.': [3758], 'Figs': [3766], 'EV2A.': [3769], 'inhibits': [3777, 4340], 'BM-derived': [3782, 3791, 3822, 4345], 'have': [3786], 'extensively': [3788], 'context': [3796], 'thus': [3814], 'detail,': [3825], '3A': [3829], 'experimental': [3831], 'C).': [3842], 'CD11b+F4/80+': [3843], 'generated': [3846, 3870, 4172], 'comparably': [3847], 'cultures,': [3852], 'similar': [3854], 'yields': [3856, 4424], '3B).': [3861], 'Virtually': [3862], 'identical': [3863], 'observed': [3866], 'BM': [3868, 3891, 3926, 3954, 4351, 4353], 'EV3A).': [3874], 'us': [3878], 'conclude': [3880], 'grossly': [3886], 'alter': [3887], 'course': [3889], 'powerful': [3897], 'signal,': [3899], 'relevant': [3900], 'chronic': [3902], 'diseases.': [3903], 'knockdown': [3909], 'individual': [3911], 'proteins': [3913, 4206, 4238], 'decreases': [3919], 'certain': [3922], 'determine': [3942], 'definitively,': [3948], 'RNA-seq': [3951, 4129, 4447], 'stimulated': [3956], 'h.': [3961], 'defined': [3963], 'threshold': [3977], 'set': [3978], 'FDR': [3980], '0.1': [3982], 'following': [3983], 'DESeq2': [3985], 'program': [3986], '(Robinson': [3987], '2009).': [3990], 'Since': [3991, 4203], 'affects': [3994], 'assessed': [3997], 'disruption': [4000], 'changes': [4001], 'global': [4002, 4045], 'expression.': [4004], 'plotted': [4006], 'linear': [4007], 'regression': [4008], 'RPKM': [4013], 'values': [4014], '(log2': [4015], 'LPS/UT': [4016], '≥': [4017], '1)': [4018], 'S3A).': [4027], 'conditions': [4033, 4083], 'correlated': [4036], '(slope': [4037], '=': [4038], '0.987).': [4039], 'Given': [4040], 'modest': [4042], 'intercept,': [4043], 'likely': [4051], 'be': [4053], 'low.': [4054], 'MA': [4055, 4444], 'plots': [4056, 4445], '3C': [4059], 'panels)': [4063], 'upregulated': [4071, 4117], 'compared': [4075, 4284], 'under': [4080], 'untreated': [4081, 4402, 4450], '(UT)': [4082, 4451], 'stimulation.': [4087], 'More': [4088], 'importantly,': [4089], 'induced': [4092], '868': [4093], '(Venn': [4098], '3D).': [4102], 'Of': [4103], 'them,': [4104], '206': [4105], '12': [4114], 'independently': [4124], 'prepared': [4125], 'samples': [4126], 'data,': [4130], 'Tnf,': [4132], 'Il1b': [4133], '(genes': [4134], 'unaffected': [4135], 'KO),': [4137, 4143], 'Ptgs2,': [4138], 'Fcgr2b,': [4139], 'Il6': [4140], '(downregulated': [4141, 4259], 'Ccl2': [4145], 'Ccl7': [4147], '(upregulated': [4148], 'KO)': [4150], '3E).': [4152], 'only': [4154], '~25%': [4155], 'agreement': [4165], 'inhibition,': [4169], 'partial': [4177], 'inhibition': [4178], '(13%)': [4179], 'EV3B': [4184], 'C,': [4186], 'EV3D).': [4192], '70%': [4199], 'affect': [4210], 'proinflammatory': [4211], 'expression,': [4213], 'BRD2': [4218], 'BRD3': [4220], 'Immunoblot': [4229], 'data': [4230, 4448], 'EV3E': [4233], 'slightly': [4242], 'higher': [4243], 'mechanism.': [4253], 'analysis,': [4256], 'BRD4-dependent': [4257, 4305], 'knockout)': [4262, 4268], 'BRD4-independent': [4264], '(unaffected': [4266], 'interferon': [4274], 'among': [4276], 'others': [4277], '(Figs': [4278], '3F': [4279], 'EV3F).': [4281], 'Finally,': [4282], 'reported': [4294], 'earlier': [4295], '2010),': [4299], '25%': [4303], 'drug': [4314], 'S3B).': [4317], 'part': [4331], 'through': [4332], 'different': [4333], 'mechanisms.': [4334], '3.': [4336], 'scheme': [4348], 'generating': [4350], 'cultured': [4361], 'M-CSF': [4366], '7': [4368, 4400], 'tamoxifen': [4378], '(see': [4380], 'verification': [4384], 'deletion).': [4387], 'harvested': [4397], 'day': [4399], 'tamoxifen-treated': [4405], 'cultures': [4407], 'Histogram': [4409], 'depicting': [4410], 'Total': [4420], 'calculated': [4425], '15': [4428], 'experiments.': [4430], '21': [4436], '24': [4439], 'LPS-treated': [4453], '(4': [4454], 'h)': [4455], 'Diffe': [4460]}, 'cited_by_api_url': 'https://api.openalex.org/works?filter=cites:W2920620505', 'counts_by_year': [{'year': 2024, 'cited_by_count': 18}, {'year': 2023, 'cited_by_count': 16}, {'year': 2022, 'cited_by_count': 18}, {'year': 2021, 'cited_by_count': 28}, {'year': 2020, 'cited_by_count': 16}, {'year': 2019, 'cited_by_count': 5}], 'updated_date': '2024-12-08T11:34:05.307714', 'created_date': '2019-03-11'}
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