STAT3依赖的长非编码RNA Lncenc1通过稳定KmRNA促进小鼠ES细胞的多能性。

IF 4.6 Q2 MATERIALS SCIENCE, BIOMATERIALS ACS Applied Bio Materials Pub Date : 2024-09-27 DOI:10.1093/bfgp/elad045
Emanuele Monteleone, Paola Corrieri, Paolo Provero, Daniele Viavattene, Lorenzo Pulvirenti, Laura Raggi, Elena Carbognin, Marco E Bianchi, Graziano Martello, Salvatore Oliviero, Pier Paolo Pandolfi, Valeria Poli
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引用次数: 0

摘要

胚胎干细胞(ESCs)依靠调节多能性转录因子及其靶标的表达/活性的细胞外信号的复杂相互作用,在保持其自我更新潜力的同时,保持分化为任何体细胞谱系的独特能力。白血病抑制因子(LIF)激活的STAT3通过多种机制驱动ESCs的干性,包括Klf4等多能性因子的转录诱导和干细胞样表观遗传景观的维持。然而,尚不清楚STAT3是否直接控制干细胞特异性非编码RNA,这对平衡多能性和分化至关重要。应用生物信息学管道,我们将小鼠ESCs中的Lncenc1鉴定为支持多能性的STAT3依赖性长非编码RNA。Lncenc1在细胞质中作为LIF-STAT3轴的正反馈调节因子,通过竞争微小RNA-128与Klf4核心多能因子mRNA的3’UTR的结合,增强其表达。我们的研究结果揭示了一种新的基于非编码RNA的LIF-STAT3介导的多能性机制。
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STAT3-dependent long non-coding RNA Lncenc1 contributes to mouse ES cells pluripotency via stabilizing Klf4 mRNA.

Embryonic stem cells (ESCs) preserve the unique ability to differentiate into any somatic cell lineage while maintaining their self-renewal potential, relying on a complex interplay of extracellular signals regulating the expression/activity of pluripotency transcription factors and their targets. Leukemia inhibitory factor (LIF)-activated STAT3 drives ESCs' stemness by a number of mechanisms, including the transcriptional induction of pluripotency factors such as Klf4 and the maintenance of a stem-like epigenetic landscape. However, it is unknown if STAT3 directly controls stem-cell specific non-coding RNAs, crucial to balance pluripotency and differentiation. Applying a bioinformatic pipeline, here we identify Lncenc1 in mouse ESCs as an STAT3-dependent long non-coding RNA that supports pluripotency. Lncenc1 acts in the cytoplasm as a positive feedback regulator of the LIF-STAT3 axis by competing for the binding of microRNA-128 to the 3'UTR of the Klf4 core pluripotency factor mRNA, enhancing its expression. Our results unveil a novel non-coding RNA-based mechanism for LIF-STAT3-mediated pluripotency.

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来源期刊
ACS Applied Bio Materials
ACS Applied Bio Materials Chemistry-Chemistry (all)
CiteScore
9.40
自引率
2.10%
发文量
464
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