Myb permits multilineage airway epithelial cell differentiation.
Myb permits multilineage airway epithelial cell differentiation.
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DOI：
10.1002/stem.1814
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发表时间：
2014-12
期刊：
影响因子：
5.2
通讯作者：
Brody, Steven L.
中科院分区：
文献类型：
--
作者：
Pan, Jie-Hong;Adair-Kirk, Tracy L.;Patel, Anand C.;Huang, Tao;Yozamp, Nicholas S.;Xu, Jian;Reddy, E. Premkumar;Byers, Derek E.;Pierce, Richard A.;Holtzman, Michael J.;Brody, Steven L.
关键词：
肺气道上皮细胞经过特殊分化，以抵御环境污染，但也受到导致肺部疾病的分化失调的影响。目前的呼吸道上皮细胞分化模式是一步法，即p63+的基本上皮祖细胞产生纤毛或分泌细胞谱系，但这一转变的线索以及是否存在中间步骤尚未明确。在这里，我们确定转录因子Myb是允许呼吸道上皮细胞早期多系分化的关键调节因子。MYB+细胞被鉴定为p63−，因此有别于基础祖细胞，但分化标志物仍为阴性。MYB RNAi处理原代培养的小鼠呼吸道上皮细胞和Myb基因缺失导致p63−群体Foxj1+纤毛细胞以及Scbg1a1+和Muc5ac+分泌细胞成熟失败。与这些发现一致的是，对Myb缺陷细胞的全基因组表达的分析确定了纤毛细胞和分泌细胞分化的Myb依赖程序。MYB+细胞在人类呼吸道中很少见，但在慢性阻塞性肺疾病患者的纤毛细胞和粘液细胞增生区增加。总之，结果表明，p63−Myb+的呼吸道上皮细胞群体代表了一个明显的分化中间阶段，这在正常情况下是必需的，在呼吸道疾病中可能会增强。
The epithelium of the pulmonary airway is specially differentiated to provide defense against environmental insults, but also subject to dysregulated differentiation that results in lung disease. The current paradigm for airway epithelial differentiation is a one-step program whereby a p63+ basal epithelial progenitor cell generates a ciliated or secretory cell lineage, but the cue for this transition and whether there are intermediate steps is poorly defined. Here we identify transcription factor Myb as a key regulator that permits early multilineage differentiation of airway epithelial cells. Myb+ cells were identified as p63− and therefore distinct from basal progenitor cells, but were still negative for markers of differentiation. Myb RNAi treatment of primary-culture airway epithelial cells and Myb gene deletion in mice resulted in a p63− population with failed maturation of Foxj1+ ciliated cells, as well as Scbg1a1+ and Muc5ac+ secretory cells. Consistent with these findings, analysis of whole genome expression of Myb-deficient cells identified Myb-dependent programs for ciliated and secretory cell differentiation. Myb+ cells were rare in human airways but were increased in regions of ciliated cells and mucous cell hyperplasia in samples from subjects with chronic obstructive pulmonary disease. Together, the results show that a p63− Myb+ population of airway epithelial cells represents a distinct intermediate stage of differentiation that is required under normal conditions and may be heightened in airway disease.
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影响因子：
3.7
作者：
Hackett NR;Shaykhiev R;Walters MS;Wang R;Zwick RK;Ferris B;Witover B;Salit J;Crystal RG
通讯作者：
Crystal RG
影响因子：
8
作者：
Ess, KC;Witte, DP;Aronow, BJ
通讯作者：
Aronow, BJ
影响因子：
9.6
作者：
Deslee G;Woods JC;Moore C;Conradi SH;Gierada DS;Atkinson JJ;Battaile JT;Liu L;Patterson GA;Adair-Kirk TL;Holtzman MJ;Pierce RA
通讯作者：
Pierce RA
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y
DOI：
10.1183/09031936.00123008
发表时间：
2009-08
期刊：
The European respiratory journal
影响因子：
--
作者：
Deslee G;Woods JC;Moore CM;Liu L;Conradi SH;Milne M;Gierada DS;Pierce J;Patterson A;Lewit RA;Battaile JT;Holtzman MJ;Hogg JC;Pierce RA
通讯作者：
Pierce RA