Induction of Pluripotent Stem Cells from Mouse Embryonic Fibroblasts by Jdp2-Jhdm1b-Mkk6-Glis1-Nanog-Essrb-Sall4

Wang, Bo; Wu, Linlin; Li, Dongwei; Liu, Yuting; Guo, Jing; Li, Chen; Yao, Yuxiang; Wang, Yaofeng; Zhao, Guoqing; Wang, Xiaoshan; Fu, Meijun; Li, He; Cao, Shuiyan; Wu, Chuman; Yu, Shengyong; Zhou, Chunhua; Qin, Yue; Kuang, Jinqiang; Jin, Ming; Chu, Shilong; Yang, Xuejie; Zhu, Ping; Pan, Guangjin; Chen, Jiekai; Liu, Jing; Pei, Duanqing

doi:10.1016/j.celrep.2019.05.068

Cited by 49 publications

(50 citation statements)

References 22 publications

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“…TF signatures of PF-NSC-like cells included JUN , FOS , and ATF3 , all of which are also top signature genes of this subpopulation ( Figure 2 E). Other TF regulons with high activity in PF-NSC-like cells were SRF and JDP2 , both of which are implicated in repression of cell differentiation and pluripotency induction ( Figure 2 E) ( Wang et al., 2019a ; Ikeda et al., 2018 ). The PF-Neuronal-Precursor-like program also showed a selective TF signature including NEUROG1/2 and ARID3A ( Figure 2 E), described to regulate neurogenesis ( Han et al., 2018 ) and promote oncogenic stemness ( Dausinas et al., 2020 ).…”

Section: Resultsmentioning

confidence: 99%

Single-Cell RNA-Seq Reveals Cellular Hierarchies and Impaired Developmental Trajectories in Pediatric Ependymoma

et al. 2020

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Summary Ependymoma is a heterogeneous entity of central nervous system tumors with well-established molecular groups. Here, we apply single-cell RNA sequencing to analyze ependymomas across molecular groups and anatomic locations to investigate their intratumoral heterogeneity and developmental origins. Ependymomas are composed of a cellular hierarchy initiating from undifferentiated populations, which undergo impaired differentiation toward three lineages of neuronal-glial fate specification. While prognostically favorable groups of ependymoma predominantly harbor differentiated cells, aggressive groups are enriched for undifferentiated cell populations. The delineated transcriptomic signatures correlate with patient survival and define molecular dependencies for targeted treatment approaches. Taken together, our analyses reveal a developmental hierarchy underlying ependymomas relevant to biological and clinical behavior.

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Section: Resultsmentioning

confidence: 99%

Single-Cell RNA-Seq Reveals Cellular Hierarchies and Impaired Developmental Trajectories in Pediatric Ependymoma

et al. 2020

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“…The above analysis has revealed the well-ordered dynamic expression of TEs in developmental processes, we then wondered if TEs undergo similar stage-specific regulation during somatic reprogramming. Somatic cells can be reprogrammed to induced pluripotent stem cells (iPSCs) by various methods, such as ectopic expression of a group of pluripotency transcription factors 25,46,47 , or cocktails of chemicals 48,49 . The reprogramming process is highly heterogeneous, with abundant non-reprogramming cells and divergent cell fate transition routes 25,50 .…”

Section: Resultsmentioning

confidence: 99%

Unveiling transposable element expression heterogeneity in cell fate regulation at the single-cell level

Babarinde

Sun

et al. 2020

Preprint

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Transposable elements (TEs) make up a majority of a typical eukaryote’s genome, and contribute to cell heterogeneity and fate in unclear ways. Single cell-sequencing technologies are powerful tools to explore cells, however analysis is typically gene-centric and TE activity has not been addressed. Here, we developed a single-cell TE processing pipeline, scTE, and report the activity of TEs in single cells in a range of biological contexts. Specific TE types were expressed in subpopulations of embryonic stem cells and were dynamically regulated during pluripotency reprogramming, differentiation, and embryogenesis. Unexpectedly, TEs were expressed in somatic cells, including human disease-specific TEs that are undetectable in bulk analyses. Finally, we applied scTE to single cell ATAC-seq data, and demonstrate that scTE can discriminate cell type using chromatin accessibly of TEs alone. Overall, our results reveal the dynamic patterns of TEs in single cells and their contributions to cell fate and heterogeneity.

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“…Furthermore, SP8 was shown to enhance the recruitment of β-catenin, a co-activator that stimulates the expression of Wnt target genes 36 . Of note, SP8 has recently been identified as a downstream target which is activated by Nanog at day 5 of reprogramming 37 . This upregulation of SP8 was consistent with our data that showed that the SP8 gene stays upregulated through reprogramming and selfrenewal stages (passage 8).…”

Section: Discussionmentioning

confidence: 99%

Identification of potential transcription factors that enhance human iPSC generation

Swaidan

Salloum-Asfar

Palangi

et al. 2020

Sci Rep

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Although many factors have been identified and used to enhance the iPSC reprogramming process, its efficiency remains quite low. In addition, reprogramming efficacy has been evidenced to be affected by disease mutations that are present in patient samples. In this study, using RNA-seq platform we have identified and validated the differential gene expression of five transcription factors (TFs) (GBX2, NANOGP8, SP8, PEG3, and ZIC1) that were associated with a remarkable increase in the number of iPSC colonies generated from a patient with Parkinson's disease. We have applied different bioinformatics tools (Gene ontology, protein–protein interaction, and signaling pathways analyses) to investigate the possible roles of these TFs in pluripotency and developmental process. Interestingly, GBX2, NANOGP8, SP8, PEG3, and ZIC1 were found to play a role in maintaining pluripotency, regulating self-renewal stages, and interacting with other factors that are involved in pluripotency regulation including OCT4, SOX2, NANOG, and KLF4. Therefore, the TFs identified in this study could be used as additional transcription factors that enhance reprogramming efficiency to boost iPSC generation technology.

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Induction of Pluripotent Stem Cells from Mouse Embryonic Fibroblasts by Jdp2-Jhdm1b-Mkk6-Glis1-Nanog-Essrb-Sall4

Abstract: Highlights d Jdp2, Jhdm1b, Mkk6, Glis1, Nanog, Esrrb, and Sall4 (7F) convert MEFs into iPSCs d RNA-seq and ATAC-seq reveal a distinct path for 7F reprogramming d 7F cooperate to open and close chromatin during 7F reprogramming d 7F activate a TF network to induce pluripotency

Cited by 49 publications

References 22 publications

Single-Cell RNA-Seq Reveals Cellular Hierarchies and Impaired Developmental Trajectories in Pediatric Ependymoma

Single-Cell RNA-Seq Reveals Cellular Hierarchies and Impaired Developmental Trajectories in Pediatric Ependymoma

Unveiling transposable element expression heterogeneity in cell fate regulation at the single-cell level

Identification of potential transcription factors that enhance human iPSC generation

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