Conditional control of the differentiation competence of pancreatic endocrine and ductal cells by Fgf10.
Conditional control of the differentiation competence of pancreatic endocrine and ductal cells by Fgf10.
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DOI：
10.1016/j.mod.2009.11.005
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发表时间：
2010-04
影响因子：
2.6
通讯作者：
Jensen, Jan
中科院分区：
文献类型：
--
作者：
Kobberup, Sune;Schmerr, Martin;Dang, My-Linh;Nyeng, Pia;Jensen, Jan N.;MacDonald, Raymond J.;Jensen, Jan
fgf 10是内胚层发育过程中间充质-上皮细胞信号传导的重要组成部分。在Fgf 10缺失胰腺中，胚胎祖细胞群体未能扩增，而异位Fgf 10表达迫使祖细胞停滞和器官增生。使用条件性Fgf 10功能获得模型，我们观察到Fgf 10表达的时间影响了被逮捕的胰腺祖细胞的细胞能力。我们目前的证据表明，FGF 10-逮捕祖细胞状态是可逆的，终末分化FGF 10生产停止后恢复。然而，对单个胰腺细胞谱系的能力取决于Fgf 10表达减弱的妊娠时间。这揭示了内分泌和导管细胞形成的能力窗口，与E13.5和E15.5之间的胰腺次级转变相一致。我们证明，在此期间，保持FGF 10的逮捕状态导致永久丧失的能力，内分泌和导管细胞的命运。然而，能力的逮捕祖细胞对外分泌细胞的命运保留在整个二级过渡。持续的Fgf 10表达引起Ngn 3表达的不可逆损失，这可能是内分泌能力丧失的基础。外分泌能力的维持可能归因于连续Ptf 1a在FGF 10-被捕祖细胞中的表达。这可能解释了在异位Fgf 10表达丧失后，Bhlhb 8（一种正常远端化的细胞内在标志物）的快速诱导。我们的结论是内分泌和导管细胞能力的窗口停止在胰腺发育的第二个过渡。
Fgf10 is a critical component of mesenchymal-to-epithelial signaling during endodermal development. In the Fgf10 null pancreas, the embryonic progenitor population fails to expand, while ectopic Fgf10 expression forces progenitor arrest and organ hyperplasia. Using a conditional Fgf10 gain-of-function model, we observed that the timing of Fgf10 expression affected the cellular competence of the arrested pancreatic progenitors. We present evidence that the Fgf10-arrested progenitor state is reversible and that terminal differentiation resumes upon cessation of Fgf10 production. However, competence towards the individual pancreatic cell lineages depended upon the gestational time of when Fgf10 expression was attenuated. This revealed a competence window of endocrine and ductal cell formation that coincided with the pancreatic secondary transition between E13.5 and E15.5. We demonstrate that maintaining the Fgf10-arrested state during this period leads to permanent loss of competence for the endocrine and ductal cell fates. However, competence of the arrested progenitors towards the exocrine cell fate was retained throughout the secondary transition. Sustained Fgf10 expression caused irreversible loss of Ngn3 expression, which may underlie the loss of endocrine competence. Maintenance of exocrine competence may be attributable to continuous Ptf1a expression in the Fgf10-arrested progenitors. This may explain the rapid induction of Bhlhb8, a normally distalized cell intrinsic marker, following loss of ectopic Fgf10 expression. We conclude that the window for endocrine and ductal cell competence ceases during the secondary transition in pancreatic development.
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影响因子：
3.2
作者：
Hald, Jacob;Sprinkel, Anne Ejrnaes;Madsen, Ole D.
通讯作者：
Madsen, Ole D.
DOI：
10.1073/pnas.96.11.6267
发表时间：
1999-05-25
影响因子：
11.1
作者：
Miralles, F;Czernichow, P;Scharfmann, R
通讯作者：
Scharfmann, R
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29
作者：
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通讯作者：
Nakao, K
影响因子：
64.8
作者：
Apelqvist, Å;Li, H;Edlund, H
通讯作者：
Edlund, H
影响因子：
5.3
作者：
Jacquemin, P;Durviaux, SM;Lemaigre, FP
通讯作者：
Lemaigre, FP