Efficient derivation of purified lung and thyroid progenitors from embryonic stem cells.
Efficient derivation of purified lung and thyroid progenitors from embryonic stem cells.
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DOI：
10.1016/j.stem.2012.01.019
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发表时间：
2012-04-06
期刊：
影响因子：
23.9
通讯作者：
Kotton, Darrell N.
中科院分区：
文献类型：
--
作者：
Longmire, Tyler A.;Ikonomou, Laertis;Hawkins, Finn;Christodoulou, Constantina;Cao, Yuxia;Jean, J. C.;Kwok, Letty W.;Mou, Hongmei;Rajagopal, Jayaraj;Shen, Steven S.;Dowton, Anne A.;Serra, Maria;Weiss, Daniel J.;Green, Michael D.;Snoeck, Hans-Willem;Ramirez, Maria I.;Kotton, Darrell N.
在发育中的前肠内胚层中，两群Nkx2 - 1阳性祖细胞产生了整个出生后的肺和甲状腺上皮细胞，但人们对这些细胞知之甚少，因为它们很难以纯的形式被分离出来。我们在此展示了源自小鼠胚胎干细胞（ESCs）的原始肺和甲状腺祖细胞的纯化以及定向分化。抑制TGFβ和BMP信号传导，接着联合刺激BMP和FGF信号传导，能够从定型内胚层前体细胞中有效地确定这些细胞。当使用Nkx2 - 1GFP基因敲入报告ESCs来获取这些细胞时，这些祖细胞可以被纯化以便在培养中扩增，并且其转录组与发育中的肺上皮细胞有重叠。在诱导时，它们能够表达一系列广泛的标志基因，这些基因表明了肺和甲状腺谱系，并且能够使三维肺组织支架重新细胞化。因此，我们获得了一群纯的祖细胞，它们能够重现肺/甲状腺发育的关键阶段。
Two populations of Nkx2-1+ progenitors in the developing foregut endoderm give rise to the entire post-natal lung and thyroid epithelium, but little is known about these cells, as they are difficult to isolate in a pure form. We demonstrate here the purification and directed differentiation of primordial lung and thyroid progenitors derived from mouse embryonic stem cells (ESCs). Inhibition of TGFβ and BMP signaling, followed by combinatorial stimulation of BMP and FGF signaling can specify these cells efficiently from definitive endodermal precursors. When derived using Nkx2-1GFP knock-in reporter ESCs, these progenitors can be purified for expansion in culture and have a transcriptome that overlaps with developing lung epithelium. Upon induction, they can express a broad repertoire of markers indicative of lung and thyroid lineages and can recellularize a 3D lung tissue scaffold. Thus, we have derived a pure population of progenitors able to recapitulate the developmental milestones of lung/thyroid development.
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DOI：
10.1152/ajplung.00127.2002
发表时间：
2002-11-01
影响因子：
4.9
作者：
Gonzales, LW;Guttentag, SH;Ballard, PL
通讯作者：
Ballard, PL
影响因子：
4.6
作者：
Domyan, Eric T.;Ferretti, Elisabetta;Sun, Xin
通讯作者：
Sun, Xin
DOI：
10.1073/pnas.0902274106
发表时间：
2009-09-22
影响因子：
11.1
作者：
Harris-Johnson, Kelley S.;Domyan, Eric T.;Sun, Xin
通讯作者：
Sun, Xin
影响因子：
46.9
作者：
Gouon-Evans, Valerie;Boussemart, Lise;Keller, Gordon
通讯作者：
Keller, Gordon
影响因子：
4.8
作者：
Lü, JN;Izvolsky, KI;Cardoso, WV
通讯作者：
Cardoso, WV