Krüppel-like factor 5 rewires NANOG regulatory network to activate human naive pluripotency specific LTR7Ys and promote naive pluripotency

Ai, Zhipeng; Xiang, Xinyu; Xiang, Yangquan; Szczerbinska, Iwona; Qian, Yuping; Xu, Xiao; Ma, Chao; Su, Yaqi; Gao, Bing; Shen, Hao; Ramli, Muhammad Nadzim Bin; Chen, Di; Liu, Yue; Hao, Jia‐Jie; Ng, Huck Hui; Zhang, Dan; Chan, Yun‐Shen; Liu, Wanlu; Liang, Hongqing

doi:10.1016/j.celrep.2022.111240

Cited by 11 publications

(17 citation statements)

References 80 publications

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“…Although the answer is not yet clear, one relevant observation relates to chromatin accessibility. KLF5 may render chromatin at HERVH loci more accessible to other transcription factors, as this pattern has been seen in naive ES cell cultures (24).…”

Section: Hervh-calb1 Is Expressed In the Pluripotent Epiblastmentioning

confidence: 78%

Staring at the onco-exaptation: the two-faced medley of an ancient retrovirus, HERVH

Singh,

Kondraskhina,

Hurst

et al. 2023

Journal of Clinical Investigation

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Communication between cancer cells and antitumor immune responsesEscaping senescence is thought to be a necessary step in cancer initiation (1). However, senescence is a double-edged sword, as this cellular stage is associated with the senescence-associated secretory phenotype (SASP), characterized by activated chemokine-signaling pathways (2) that correlate with neutrophil infiltration and worse prognosis. Lung squamous cell carcinoma (LUSC) is a type of lung cancer that persists globally among the main causes of cancer-related death in the world. The classical therapy for LUSC patients includes surgical removal of carcinomas, followed by radiotherapy and/ or chemotherapy (3). A more personalized therapy utilizes a tailored approach by inhibiting molecular pathways that target patient-specific driver mutations, which in LUSC are restricted to only two oncogenes (NTRK, MET), whereas in other lung cancers, a larger number of target oncogenes are known (3). Recently, immune checkpoint inhibitors (ICIs) have been used to activate the immune systems of patients to destroy tumor cells (4). Despite the considerable potential of immune treatments, only approximately 20% of patients respond to them (3), urging a better understanding of cellular heterogeneity and communication between cancer cells and antitumor immune responses.

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Section: Hervh-calb1 Is Expressed In the Pluripotent Epiblastmentioning

confidence: 78%

Staring at the onco-exaptation: the two-faced medley of an ancient retrovirus, HERVH

Singh,

Kondraskhina,

Hurst

et al. 2023

Journal of Clinical Investigation

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“…KLF5, DPPA2, TFAP2C) and of NANOG, repression of the conventional markers ZIC2, but no significant changes in trophoblast markers (Figure 6e). Of note, TFAP2C has been shown to be required for maintenance and induction of naive pluripotency 44 , KLF5 for maintenance of naive pluripotency 24 , and NANOG for both maintenance and induction of pluripotency 15 .…”

Section: Resultsmentioning

confidence: 99%

“…In human naive cells, KLF4, KLF5 and KLF17 are highly expressed [22][23][24] , but their expression in conventional/primed PSCs remains unexplored. Analysis of human preand post-implantation epiblast cells indicate that these Kruppel-like factors are expressed specifically in the naive state 25 .…”

Section: Introductionmentioning

confidence: 99%

KLF7 is a general inducer of human pluripotency

Arboit,

Zorzan,

Pellegrini

et al. 2023

Preprint

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Pluripotency is the capacity to give rise to all differentiated cells of the body and the germ line and is governed by a self-reinforcing network of transcription factors. The forced expression of only some of these factors enables the reprogramming of somatic cells to pluripotency. In murine cells, several kruppel-like factors (KLFs) have been identified as stabilisers and inducers of pluripotency. Human somatic cells are routinely reprogrammed by expression of KLF4 in combination with OCT4, SOX2 and cMYC (OSKM). An extensive transcriptome analysis revealed, however, that KLF4 is barely expressed in conventional human pluripotent stem cells (PSCs). Here we show that KLF7 is robustly expressed in conventional human PSCs and it allows transcription factor-mediated somatic reprogramming. Moreover, we find that KLF7 is highly expressed in naive PSCs and its forced expression in conventional hPSCs induces upregulation of naive markers and boosts efficiency of chemical resetting to naive PSCs, overall suggesting that KLF7 is a general human pluripotency factor and an inducer of pluripotency.

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“…Previous studies have indicated that the dynamic expression of TEs could serve as a hallmark for human naïve and primed hESC 45,46 , and our earlier research has highlighted their potential functional roles in hESC cell fate determination 28,47 .…”

Section: Comparative Analyses With Experimental Datasetsmentioning

confidence: 87%

“…With this paired naïve and primed hESCs TGS RNA-seq dataset, along with our previously published NGS RNA-seq datasets derived from the same conditions, we also performed comprehensive downstream differential isoform usage (DIU) evaluation and experimentally validated one of the DIU isoforms from RPL39L (Ribosomal Protein L39 Like) gene using qRT-PCR (Real-Time Quantitative Reverse Transcription PCR) 28 . Furthermore, we assessed the computational performance of the software by evaluating time and memory consumption using an in-house developed profiler.…”

Section: Introductionmentioning

confidence: 99%

Comprehensive Assessment of Isoform Detection Methods for Third-Generation Sequencing Data

Jin

et al. 2023

Preprint

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The advancement of Third-Generation Sequencing (TGS) techniques has significantly increased the length of sequencing to several kilobases, thereby facilitating the identification of alternative splicing (AS) events and isoform expressions. Recently, numerous computational methods for isoform detection using long-read sequencing data have been developed. However, there is lack of prior comparative studies that systemically evaluates the performance of these software tools, implemented with different algorithms, under various simulations that encompass potential influencing factors. In this study, we conducted a benchmarking analysis of eleven methods implemented in eight computational tools capable of identifying isoform structures from TGS RNA sequencing data. We evaluated their performances using simulated data, which represented diverse sequencing platforms generated by an in-house simulator, as well as experimental data. Our comprehensive results demonstrate the guided mode of StringTie2 and Bambu achieved the best performance in sensitivity and precision, respectively. This study provides valuable guidance for future research on AS analysis and the ongoing improvement of tools for isoform detection using TGS data.

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Krüppel-like factor 5 rewires NANOG regulatory network to activate human naive pluripotency specific LTR7Ys and promote naive pluripotency

Cited by 11 publications

References 80 publications

Staring at the onco-exaptation: the two-faced medley of an ancient retrovirus, HERVH

Staring at the onco-exaptation: the two-faced medley of an ancient retrovirus, HERVH

KLF7 is a general inducer of human pluripotency

Comprehensive Assessment of Isoform Detection Methods for Third-Generation Sequencing Data

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