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Cell Stem Cell:Bmi-1调控神经干细胞自我更新的新靶标被发现

来源:生物谷 2007-06-27 21:11

生物谷报道:研究发现Bmi-1基因对于调控出生后的神经干细胞的自我更新具有关键作用,并且以细胞周期抑制蛋白p16p19为分子靶标。最近,一项新的研究发现,Bmi-1同样可以调控胚胎中神经干细胞的自我更新,并且其调控过程与细胞周期调控信号通路p21-Rb具有密切关系。这一结果发表在最新一期《细胞-干细胞》杂志上。

研究人员发现,神经祖细胞的增殖对Bmi-1的依赖从胚胎期到成体期逐渐增强。急性shRNA介导的Bmi-1表达下降会导致胚胎和成体神经干细胞增殖和自我更新的缺陷。此外,研究人员意外地首次发现,这种调控受到细胞周期抑制因子p21的调节。这意味着p21在神经干细胞中是Bmi-1的一个重要靶分子。揭示p21在神经干细胞自我更新中的作用机制将有助于未来干细胞疗法的发展,因而具有重要的意义。

 

 

Figure 1. shRNA against Bmi-1 Is Effective and Specific in NPCs

(A) Diagram of the shRNA-expressing and Bmi-1-expressing lentiviral constructs.

(B) E11 NPCs from E11 cortices were transduced with control or different Bmi-1 shRNA lentivectors and then cultured in adherent conditions for 48 hr. mRNA was isolated and real-time quantitative PCR was performed to determine the level of Bmi-1 transcripts. Expression levels were normalized for GAPDH. Error bars, SD between four experiments.

(C) Western blot of protein samples isolated from E11 cortical NPCs transduced with EV control, Bmi-1 ORF shRNA, Bmi-1 3′UTR shRNA, or pUbqC-Bmi-1 (expression) lentiviruses.

(D) Frequency of primary neurospheres assessed at 7 days, at which point they were passaged and secondary neurosphere frequency was assessed at a further 7 days. Neurosphere frequencies were normalized to mock-transduced cells. Error bars, SE from four experiments. ANOVA was used with Bonferonni post-hoc test., #p < 0.05, p < 0.001 compared to mock control.

(E) Secondary neurosphere frequencies after lentiviral transduction of E11 cortical progenitors with shRNA Bmi-1 3′UTR are different from EV control, p < 0.0001 and #p < 0.05. Cells cotransduced with both the shRNA Bmi-1 3′UTR and pUbqC-Bmi-1 lentiviruses show no significant difference in the frequency of secondary neurospheres compared to controls.

(F) Sizes of E11 neurospheres at 7 days as percent change from control, p < 0.01, #p < 0.01.

 

原文出处:

Cell Stem Cell    June, 2007: 1 (1)

shRNA Knockdown of Bmi-1 Reveals a Critical Role for p21-Rb Pathway in NSC Self-Renewal during Development
Christopher A. Fasano, John T. Dimos, Natalia B. Ivanova, Natalia Lowry, Ihor R. Lemischka, and Sally Temple
[Summary] [Full Text] [PDF] [Supplemental Data] 

 

 

相关基因:

BMI1

Official Symbol BMI1 and Name: BMI1 polycomb ring finger oncogene [Homo sapiens]
Other Aliases: RP11-573G6.1, MGC12685, PCGF4, RNF51
Other Designations: B lymphoma Mo-MLV insertion region; B lymphoma Mo-MLV insertion region 1 homolog; flvi-2/bmi-1; murine leukemia viral (bmi-1) oncogene homolog; oncogene BMI-1; polycomb group ring finger 4
Chromosome: 10; Location: 10p11.23
Annotation: Chromosome 10, NC_000010.9 (22650145..22660193)
MIM: 164831
GeneID: 648

 

 

作者简介:

Sally Temple, Ph.D.
Professor of Neuropharmacology
& Neuroscience

Albany Medical College

Research Interest
Stem cell research
Bio
Dr.
Temple
is studying how embryonic neural progenitor cells generate the numerous, diverse, cell types of the adult CNS. These studies may lead to therapies for neurodegenerative disorders or for neural tumors. Dr.Temple has designed a culture system in which single CNS progenitor cells can divide and differentiate into clones of neurons and glial cells. This led to the identification of different classes of progenitor cells in embryonic forebrain, including one that may play a key role in brain development: multipotential stem cells. Molecular mechanisms regulating division and differentiation of brain progenitor cells will be the focus of future studies.

Education
Ph.D. - University College London
Publications
Search Google Scholar

 

 

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人类神经干细胞在成年大鼠脊髓中可以分化 

Molecular  Cell:捕捉神经干细胞分化之重要调控蛋白的3D影像 

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FASEB J:Leukotriene B4 和lipoxin A4 能刺激神经干细胞生长和分化 

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干细胞自我更新的机制 

 

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