STAT3-dependent long non-coding RNA Lncenc1 contributes to mouse ES cells pluripotency via stabilizing Klf4 mRNA.

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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Abstract

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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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。
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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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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