Single-Cell Multi-omics Sequencing of Human Early Embryos

Li, Lin; Guo, Fan; Gao, Yun; Ren, Yixuan; Yuan, Peng; Yan, Liying; Li, Rong; Lian, Ying; Li, Jingyun; Hu, Boqiang; Gao, Junpeng; Wen, Lu; Tang, Fuchou; Qiao, Jie

doi:10.1097/ogx.0000000000000639

Cited by 36 publications

(60 citation statements)

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“…Our finding that chromatin accessibility increases during genome activation, especially at promoter and enhancer elements, is consistent with recent studies in Drosophila, zebrafish, Xenopus, mouse and human embryos [4,[10][11][12][13]25,49]. An increase in the number and strength of ATAC-seq peaks over time may either be due to an increase in the number of cells in which specific regions are accessible, or an actual increase in the accessibility of specific regions in all cells of the embryo.…”

Section: Zygotic Genome Activation Is Accompanied By a Dynamic Increasupporting

confidence: 92%

Chromatin accessibility established by Pou5f3, Sox19b and Nanog primes genes for activity during zebrafish genome activation

Pálfy

Schulze

Valen

et al. 2019

Preprint

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In many organisms, early embryonic development is driven by maternally provided factors until the controlled onset of transcription during zygotic genome activation. The regulation of chromatin accessibility and its relationship to gene activity during this transition remains poorly understood. Here, we generated chromatin accessibility maps from genome activation until the onset of lineage specification. During this period, chromatin accessibility increases at regulatory elements. This increase is independent of RNA polymerase II-mediated transcription, with the exception of the hyper-transcribed miR-430 locus. Instead, accessibility often precedes the transcription of associated genes. Loss of the maternal transcription factors Pou5f3, Sox19b, and Nanog, which are known to be required for zebrafish genome activation, results in decreased accessibility at regulatory elements. Importantly, the accessibility of regulatory regions, especially when established by Pou5f3, Sox19b and Nanog, is predictive for future transcription.Our results show that the maternally provided transcription factors Pou5f3, Sox19b, and Nanog open up chromatin and prime genes for activity during zygotic genome activation in zebrafish.

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Section: Zygotic Genome Activation Is Accompanied By a Dynamic Increasupporting

confidence: 92%

Chromatin accessibility established by Pou5f3, Sox19b and Nanog primes genes for activity during zebrafish genome activation

Pálfy

Schulze

Valen

et al. 2019

Preprint

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“…1). The first step has been shown feasible at both bulk-cell and single-cell level by NOMe-seq and the other previous studies (13–16). In addition, ONT has been reported to detect 5mC at CpG sites (17, 18), based on which an in-house tool was developed to map 5mC profile at GpC sites for MeSMLR-seq data (see “Nucleosome positioning detection at the single-molecule level”).…”

Section: Resultsmentioning

confidence: 60%

Single-molecule long-read sequencing reveals the chromatin basis of gene expression

Wang

Liu

et al. 2019

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1 Genome-wide chromatin accessibility and nucleosome occupancy profiles have been widely 2 investigated, while the long-range dynamics remains poorly studied at the single-cell level. 3Here we present a new experimental approach MeSMLR-seq (methyltransferase treatment 4 followed by single-molecule long-read sequencing) for long-range mapping of nucleosomes 5 and chromatin accessibility at single DNA molecules, and thus achieve 6 comprehensive-coverage characterization of the corresponding heterogeneity. We applied 7MeSMLR-seq to haploid yeast, where single DNA molecules represent single cells, and thus 8 we could investigate the combinatorics of many (up to 356) nucleosomes at long range in 9 single cells. We illustrated the differential organization principles of nucleosomes 10 surrounding transcription start site for silently-and actively-transcribed genes, at the 11 single-cell level and in the long-range scale. The heterogeneous patterns of chromatin 12 statuses spanning multiple genes were phased. Together with single-cell RNA-seq data, we 13 quantitatively revealed how chromatin accessibility correlated with gene transcription 14 positively in a highly-heterogeneous scenario. Moreover, we quantified the openness of 15 promoters and investigated the coupled chromatin changes of adjacent genes at single DNA 16 molecules during transcription reprogramming. 17 18 19 20

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“…While RNA-sequencing has been widely used to generate gene expression profiles in a tissue and organ, it cannot distinguish diversity and complexity of cell composition. Single-cell sequencing can reveal comprehensive transcriptomics at an individual cell resolution, overcome limited tissue supply, identify novel cell types, and uncover diverse contributions of individual cells to organ formation and disease conditions (Tang et al 2009;Tang et al 2010;Haque et al 2017;Hochgerner et al 2018;Li et al 2018;Potter 2018). Therefore, in this study, we have applied the single-cell sequencing approach to examine the composition of amniotic fluid cells from normal and trisomy 18 fetuses.…”

Section: Prediction Of New Chromosome 18 Critical Regionsmentioning

confidence: 99%

Single-cell transcriptomics reveals diverse and complex gene expression alterations in human trisomy 18

Wang

Chen

et al. 2019

Preprint

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Trisomy 18, commonly known as Edward's syndrome, is the second most common autosomal trisomy among live born neonates. Multiple tissues including cardiac, abdominal, and nervous systems are affected by an extra chromosome 18. To delineate the complexity of anomalies of trisomy 18, we analyzed amniotic fluid cells from two normal and three trisomy 18 samples using single-cell transcriptomics. We identified six cell groups, which function in major tissue development such as kidney, vasculature, and smooth muscle, and display significant alterations in gene expression detected by single-cell RNA-sequencing. Moreover, we demonstrated significant gene expression changes in previously proposed trisomy 18 critical regions, and identified three new regions such as 18p11.32, 18q11, 18q21.32, which are likely associated with trisomy 18 phenotypes. Our results indicate complexity of trisomy 18 at the gene expression level and reveal genetic reasoning of diverse phenotypes in trisomy 18 patients.

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Single-Cell Multi-omics Sequencing of Human Early Embryos

Cited by 36 publications

References 0 publications

Chromatin accessibility established by Pou5f3, Sox19b and Nanog primes genes for activity during zebrafish genome activation

Chromatin accessibility established by Pou5f3, Sox19b and Nanog primes genes for activity during zebrafish genome activation

Single-molecule long-read sequencing reveals the chromatin basis of gene expression

Single-cell transcriptomics reveals diverse and complex gene expression alterations in human trisomy 18

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