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涡虫再生和干细胞维持中保守的转录后调控因子的不同需求。

Different requirements for conserved post-transcriptional regulators in planarian regeneration and stem cell maintenance.

机构信息

Department of Biophysics, Graduate School of Science, Kyoto University, Kitashirakawa-Oiwake, Sakyo-ku, Kyoto 606-8502, Japan.

出版信息

Dev Biol. 2010 May 15;341(2):429-43. doi: 10.1016/j.ydbio.2010.02.037. Epub 2010 Mar 15.


DOI:10.1016/j.ydbio.2010.02.037
PMID:20230812
Abstract

Planarian regeneration depends on the presence and precise regulation of pluripotent adult somatic stem cells named neoblasts, which differentiate to replace cells of any missing tissue. A characteristic feature of neoblasts is the presence of large perinuclear nonmembranous organelles named "chromatoid bodies", which are comparable to ribonucleoprotein structures found in germ cells of organisms across different phyla. In order to better understand regulation of gene expression in neoblasts, and potentially the function and composition of chromatoid bodies, we characterized homologues to known germ and soma ribonucleoprotein granule components from other organisms and analyzed their function during regeneration of the planarian Dugesia japonica. Expression in neoblasts was detected for 49 of 55 analyzed genes, highlighting the prevalence of post-transcriptional regulation in planarian stem cells. RNAi-mediated knockdown of two factors [ago-2 and bruli] lead to loss of neoblasts, and consequently loss of regeneration, corroborating with results previously reported for a bruli ortholog in the planarian Schmidtea mediterranea (Guo et al., 2006). Conversely, depletion mRNA turnover factors [edc-4 or upf-1], exoribonucleases [xrn-1 or xrn-2], or DEAD box RNA helicases [Djcbc-1 or vas-1] inhibited planarian regeneration, but did not reduce neoblast proliferation or abundance. We also found that depletion of cap-dependent translation initiation factors eIF-3A or eIF-2A interrupted cell cycle progression outside the M-phase of mitosis. Our results show that a set of post-transcriptional regulators is required to maintain the stem cell identity in neoblasts, while another facilitates proper differentiation. We propose that planarian neoblasts maintain pluripotency by employing mechanisms of post-transcriptional regulation exhibited in germ cells and early development of most metazoans.

摘要

涡虫再生依赖于多能成体体干细胞(称为成体神经干细胞)的存在和精确调控,这些干细胞可以分化为任何缺失组织的细胞。成体神经干细胞的一个特征是存在大的核周非膜细胞器,称为“染色质体”,与不同门的生物的生殖细胞中发现的核糖核蛋白结构相当。为了更好地理解成体神经干细胞中基因表达的调控,以及潜在的染色质体的功能和组成,我们鉴定了来自其他生物的已知生殖细胞和体细胞核糖核蛋白颗粒成分的同源物,并分析了它们在日本涡虫再生过程中的功能。在分析的 55 个基因中,有 49 个基因在成体神经干细胞中表达,这突出了转录后调控在涡虫干细胞中的普遍性。ago-2 和 bruli 两种因子的 RNAi 敲低导致成体神经干细胞的丢失,进而导致再生的丧失,这与先前在 Schmidtea mediterranea 涡虫中报道的 bruli 同源物的结果相吻合(Guo 等人,2006)。相反,mRNA 周转因子 [edc-4 或 upf-1]、外切核酸酶 [xrn-1 或 xrn-2] 或 DEAD 盒 RNA 解旋酶 [Djcbc-1 或 vas-1] 的耗竭抑制了涡虫再生,但不会减少成体神经干细胞的增殖或丰度。我们还发现,帽依赖性翻译起始因子 eIF-3A 或 eIF-2A 的耗竭会中断有丝分裂 M 期以外的细胞周期进程。我们的研究结果表明,一组转录后调控因子对于维持成体神经干细胞的干细胞特性是必需的,而另一种则促进适当的分化。我们提出,涡虫成体神经干细胞通过采用在生殖细胞和大多数后生动物的早期发育中表现出的转录后调控机制来维持多能性。

相似文献

[1]
Different requirements for conserved post-transcriptional regulators in planarian regeneration and stem cell maintenance.

Dev Biol. 2010-3-15

[2]
DjCBC-1, a conserved DEAD box RNA helicase of the RCK/p54/Me31B family, is a component of RNA-protein complexes in planarian stem cells and neurons.

Dev Dyn. 2007-12

[3]
Smed-SmB, a member of the LSm protein superfamily, is essential for chromatoid body organization and planarian stem cell proliferation.

Development. 2010-4

[4]
Cellular and molecular dissection of pluripotent adult somatic stem cells in planarians.

Dev Growth Differ. 2010-1

[5]
Expression of vasa(vas)-related genes in germline cells and totipotent somatic stem cells of planarians.

Dev Biol. 1999-2-1

[6]
Heterogeneity of chromatoid bodies in adult pluripotent stem cells of planarian Dugesia japonica.

Dev Growth Differ. 2016-2

[7]
Comprehensive gene expression analyses in pluripotent stem cells of a planarian, Dugesia japonica.

Int J Dev Biol. 2012

[8]
Multicellularity, stem cells, and the neoblasts of the planarian Schmidtea mediterranea.

Exp Cell Res. 2005-6-10

[9]
SMEDWI-2 is a PIWI-like protein that regulates planarian stem cells.

Science. 2005-11-25

[10]
A LIM-homeobox gene is required for differentiation of Wnt-expressing cells at the posterior end of the planarian body.

Development. 2011-9

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[2]
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Front Cell Dev Biol. 2024-9-23

[3]
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PLoS Biol. 2022-7

[4]
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Parasitology. 2022-9

[5]
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[6]
RNAi Screen of RING/U-Box Domain Ubiquitin Ligases Identifies Critical Regulators of Tissue Regeneration in Planarians.

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[7]
Functional analysis of ADARs in planarians supports a bilaterian ancestral role in suppressing double-stranded RNA-response.

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[8]
Regeneration of Planarian Auricles and Reestablishment of Chemotactic Ability.

Front Cell Dev Biol. 2021-11-26

[9]
A pan-metazoan concept for adult stem cells: the wobbling Penrose landscape.

Biol Rev Camb Philos Soc. 2022-2

[10]
Positional Information and Stem Cells Combine to Result in Planarian Regeneration.

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