A genetic system for tissue-specific inhibition of cell proliferation
A genetic system for tissue-specific inhibition of cell proliferation
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组织特异性抑制细胞增殖的遗传系统
DOI：
10.1242/dev.183830
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发表时间：
2020-01
期刊：
影响因子：
4.6
通讯作者：
Zhou Bin
中科院分区：
文献类型：
--
作者：
Pu Wenjuan;Han Ximeng;He Lingjuan;Li Yan;Huang Xiuzhen;Zhang Mingjun;Lv Zan;Yu Wei;Wang Qing-Dong;Cai Dongqing;Wang Jinjin;Sun Ruilin;Fei Jian;Ji Yong;Nie Yu;Zhou Bin
细胞增殖是器官发育、组织稳态和疾病进展的基本过程。同样，在损伤后，通常多个细胞谱系响应于各种信号并增殖以启动损伤组织的修复和/或重塑。在组织再生和/或疾病进展期间，在整个生物体的背景下，揭示一种细胞类型及其谱系增殖的特定作用将提供关于这些过程的有价值的信息。在这里，我们报告了一个新的遗传系统，允许细胞增殖被抑制在组织特异性的方式。我们产生了Cre或Dre诱导的p21-GFP（ip 21-GFP）转基因小鼠，使实验诱导的永久性细胞周期停滞的特定细胞系的兴趣，而遗传标记这些细胞。该系统可以抑制病原细胞增殖。我们发现，心脏成纤维细胞增殖抑制显着减少瘢痕形成，促进新血管形成和心肌细胞存活。此外，我们发现，抑制一种类型的细胞增殖（即肝细胞）诱导另一种类型的细胞（即导管细胞）在组织再生过程中的谱系转换。这些结果验证了使用ip 21-GFP小鼠作为一种新的遗传工具，在体内细胞系特异性抑制细胞增殖。突出显示的文章：诱导型p21-GFP转基因小鼠能够实验诱导的永久性细胞周期停滞和特定细胞系的遗传标记，从而研究细胞增殖对细胞命运可塑性的影响。
ABSTRACT Cellular proliferation is a basic process during organ development, tissue homeostasis and disease progression. Likewise, after injury typically multiple cell lineages respond to various cues and proliferate to initiate repair and/or remodeling of the injured tissue. Unravelling the specific role of proliferation of one cell type and its lineage in the context of the whole organism during tissue regeneration and/or disease progression would provide valuable information on these processes. Here, we report a new genetic system that allows cell proliferation to be inhibited in a tissue-specific manner. We generated Cre- or Dre-inducible p21-GFP (ip21-GFP) transgenic mice that enable experimentally induced permanent cell cycle arrest of specific cell lineages of interest, while genetically marking these cells. This system allows for the inhibition of pathogenic cell proliferation. We found that cardiac fibroblast proliferation inhibition significantly reduced scar formation, and promoted neovascularization and cardiomyocyte survival. Additionally, we found that inhibition of one type of cell proliferation (namely, hepatocytes) induces the lineage conversion of another type cells (i.e. ductal cells) during tissue regeneration. These results validate the use of ip21-GFP mice as a new genetic tool for cell lineage-specific inhibition of cell proliferation in vivo. Highlighted Article: Inducible p21-GFP transgenic mice enable experimentally induced permanent cell cycle arrest and genetic marking of specific cell lineages of interest, allowing the effects of cell proliferation on cell fate plasticity to be studied.
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DOI：
10.1126/science.1199010
发表时间：
2011-04-22
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Heallen T;Zhang M;Wang J;Bonilla-Claudio M;Klysik E;Johnson RL;Martin JF
通讯作者：
Martin JF
器官特异性血管的基因靶向
影响因子：
20.1
作者：
Pu W;He L;Han X;Tian X;Li Y;Zhang H;Liu Q;Huang X;Zhang L;Wang QD;Yu Z;Yang X;Smart N;Zhou B
通讯作者：
Zhou B
影响因子：
82.9
作者：
Zeisberg, M;Hanai, J;Kalluri, R
通讯作者：
Kalluri, R
影响因子：
20.1
作者：
Kaur, Harmandeep;Takefuji, Mikito;Wettschureck, Nina
通讯作者：
Wettschureck, Nina
影响因子：
25
作者：
Madisen L;Zwingman TA;Sunkin SM;Oh SW;Zariwala HA;Gu H;Ng LL;Palmiter RD;Hawrylycz MJ;Jones AR;Lein ES;Zeng H
通讯作者：
Zeng H