Long Noncoding RNA LncPGCR Mediated by TCF7L2 Regulates Primordial Germ Cell Formation in Chickens.
Long Noncoding RNA LncPGCR Mediated by TCF7L2 Regulates Primordial Germ Cell Formation in Chickens.
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TCF7L2介导的长非编码RNA LncPGCR调节鸡原始生殖细胞的形成
DOI：
10.3390/ani11020292
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发表时间：
2021-01-24
期刊：
影响因子：
--
通讯作者：
Li B
中科院分区：
文献类型：
--
作者：
Jiang J;Chen C;Cheng S;Yuan X;Jin J;Zhang C;Sun X;Song J;Zuo Q;Zhang Y;Chen G;Li B
原始生殖细胞（Primordial germ cells，PGCs）具有多向分化的潜能和独特的再生能力，是临床医学和组织工程研究中最有前途的种子细胞之一。然而，由于不能获得足够的PGCs来满足需求，这限制了它们的应用。我们定义了一种新的由表观遗传学介导的长链非编码RNA（lncRNA），它可以激活miR-6577- 5 p/Btrc通路促进PGCs的形成。我们建立的技术体系是一个有用的工具，以获得足够的PGCs用于科学研究。本研究对转基因动物的生产和家禽基因组印记的研究具有重要的理论和实用价值。我们相信，我们的研究将有助于农业生产，发育生物学和细胞生物学领域的研究人员。摘要虽然lncRNA已被确定为在生殖细胞的发育中发挥关键作用，但其在鸡PGCs发育中的潜在参与仍然知之甚少。通过K-means聚类分析来自胚胎干细胞（ESC）、PGCs和精原干细胞（SSC）的先前RNA-seq的差异表达的lncRNA（DEL），从中获得关键候选物lncRNA（lncRNA PGC调节子，LncPGCR）。我们证实，LncPGCR通过增加PGC标记基因（Cvh和C-kit）的表达，同时下调多能性相关基因（Nanog）在体外和体内的发展中起着积极的作用。LncPGCR的激活和表达受组蛋白乙酰化和转录因子TCF 7 L2调节。在机制上，进行拯救测定以进一步证实LncPGCR通过调节gga-miR-6577- 5 p/Btrc信号传导途径促进PGC的发育。gga-miR-6577- 5 p的吸附通过缓解Btrc表达的gga-miR-6577- 5 p依赖性抑制来激活WNT信号级联。综上所述，我们的研究发现了LncPGCR在PGCs发育中的生长加速作用，显示了潜在的LncPGCR/miR-6577- 5 p/Btrc途径。结果和发现提供了一个新的见解PGCs的发展。
Simple Summary The potential of primordial germ cells (PGCs) for multidirectional differentiation, together with their unique regeneration ability, makes them one of the most promising seed cells in clinical medicine and tissue engineering research. However, not enough PGCs can be obtained to meet the demand, which limits their application. We defined a novel long noncoding RNA (lncRNA) mediated by epigenetics, which could activate the miR-6577-5p/Btrc pathway to promote the formation of PGCs. The technical system we have established is a useful tool to obtain sufficient PGCs for scientific research. Our study offers great theoretical and practical value in the production of transgenic animals or genomic imprinting in poultry. We believe that our study will help researchers in the fields of agricultural production, developmental biology, and cell biology. Abstract Although lncRNAs have been identified as playing critical roles in the development of germ cells, their potential involvement in the development of PGCs in chickens remains poorly understood. Differentially expressed lncRNAs (DELs) from previous RNA-seq of embryonic stem cells (ESCs), PGCs, and spermatogonial stem cells (SSCs) were analyzed by K-means clustering, from which a key candidate, lncRNA (lncRNA PGC regulator, LncPGCR) was obtained. We confirmed that LncPGCR plays a positive role in the development of PGCs by increasing the expression of the PGC marker gene (Cvh and C-kit), while downregulating the pluripotency-associated gene (Nanog) in vitro and in vivo. The activation and expression of LncPGCR are regulated by histone acetylation, and transcription factor TCF7L2. Mechanistically, a rescue assay was performed to further confirm that LncPGCR contributed to the development of PGCs by regulating the gga-miR-6577-5p/Btrc signaling pathway. Adsorption of gga-miR-6577-5p activated the WNT signaling cascade by relieving the gga-miR-6577-5p-dependent inhibition of Btrc expression. Taken together, our study discovered the growth-expedited role of LncPGCR in PGCs development, showing the potential LncPGCR/miR-6577-5p/Btrc pathway. The results and findings provide a novel insight into the development of PGCs.
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