Integration of single-cell transcriptome and chromatin accessibility of early gonads development among goats, pigs, macaques, and humans

Long, Xin; Chen, Min; Fei, Hao; Kang, Jia; Wang, Nan; Wang, Yuan; Wang, Mengyue; Gao, Yuan; Duo, Lei; Zhe, Xiaoshu; He, Jingsha; Ren, Bo; Zhang, Yaoguang; Liu, Bowen; Li, Jiayi; Zhang, Qiancheng; Long, Yan; Cui, Xiuhong; Wang, Yaqing; Gui, Yaoting; Wang, Hongmei; Zhu, Lan; Liu, Dongjun; Guo, Fan; Gao, Fei

doi:10.1016/j.celrep.2022.111587

Cited by 17 publications

(19 citation statements)

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“…Single-cell multi-omics technique has greatly promoted our molecular understanding of early embryos [1][2][3][4][5][6], fetal germ cells and gonadal somatic cells [7][8][9][10][11], developing testis and ovary [12][13][14][15][16], adult testis and ovary [17][18][19][20][21][22][23][24][25][26], aging testis and ovary [27][28][29], endometrium [30,31], maternal-fetal interface [32][33][34], as well as reproductive diseases [35][36][37][38][39] in the last decade. Multiple molecular layers (including gene expression patterns, DNA methylation dynamics, and open chromatin features) have been profiled with high-throughput sequencing technology, and the data have been growing continually.…”

Section: Introductionmentioning

confidence: 99%

“…Single-cell multi-omics technique has greatly promoted our molecular understanding of early embryos [1][2][3][4][5][6][7][8][9][10][11][12][13][14] , fetal germ cells and gonadal somatic cells [15][16][17][18][19][20][21][22] , developing testis and ovary [23][24][25][26][27][28][29][30] , adult testis and ovary 26,29,[31][32][33][34][35][36][37][38] , aging testis and ovary [39][40][41] , endometrium 42,43 , maternal-fetal interface [44][45][46] , as well as reproductive diseases [47][48]…”

Section: Introductionmentioning

confidence: 99%

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SMARTdb: An Integrated Database for Exploring Single-cell Multi-omics Data of Reproductive Medicine

Liu,

Yuan,

Guo

et al. 2023

Preprint

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Single-cell multi-omics sequencing has greatly accelerated reproduction research in recent years, and the data are continually growing. However, utilizing those data resources is challenging for wet-lab researchers, and therefore a comprehensive platform for exploring single-cell multi-omics data related to reproduction is urgently needed. Here we introduce SMARTdb (single-cell multi-omics atlas of reproduction), which is an integrative and user-friendly platform for exploring molecular dynamics of reproductive development, aging, and disease, covering multi-omics, multi-species, and multi-stages. We have curated and analyzed single-cell transcriptome and epigenome data of nearly 1.8 million cells from 5 species across whole lifespan. A series of powerful functionalities are provided, such as "Query gene expression", "DIY expression plot", "DNA methylation plot", and "Epigenome browser". With SMARTdb, we found that the male germ-cell-specific expression pattern of RPL39L and RPL10L is conserved between human and other model animals. Female germ cells also highly express RPL39L in fetal stage, but gradually decrease RPL39L expression in adult stage. Moreover, DNA hypomethylation and open chromatin may regulate the specific expression pattern of RPL39L collectively in both male and female germ cells. In summary, SMARTdb is a powerful platform for convenient data mining and gaining novel insights into reproductive development, aging and disease. SMARTdb is publicly available at https://smart-db.cn.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

SMARTdb: An Integrated Database for Exploring Single-cell Multi-omics Data of Reproductive Medicine

Liu,

Yuan,

Guo

et al. 2023

Preprint

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“…More recently, a bulk RNA-sequencing (bulk RNA-seq) study of human developing gonadal tissue between 6 and 17 weeks post conception (wpc) demonstrated several expected features, such as marked upregulation of meiotic transcripts, but also some novel findings, such as an enrichment of non-coding RNAs and genes with no clear link to ovary development (e.g., neuropeptide TAC1 and neurexin NRXN3 ) 7 . A limited number of single-cell RNA-sequencing (scRNA-seq) studies have recently built upon these foundations to demonstrate important cell-cell interactions, ovary developmental pathways, and gonadal somatic and germ cells crosstalk (such as FGF9-FGFR2 and PROS1-TYRO3) 8,9 . New technologies have facilitated further multi-modal -omic analyses; particularly, the integration of single cell ATAC-sequencing (assay for transposase-accessible chromatin with sequencing) with single-cell data has elucidated novel post-transcriptional regulatory layers in the developing ovary 8,9 .…”

Section: Introductionmentioning

confidence: 99%

“…A limited number of single-cell RNA-sequencing (scRNA-seq) studies have recently built upon these foundations to demonstrate important cell-cell interactions, ovary developmental pathways, and gonadal somatic and germ cells crosstalk (such as FGF9-FGFR2 and PROS1-TYRO3) 8,9 . New technologies have facilitated further multi-modal -omic analyses; particularly, the integration of single cell ATAC-sequencing (assay for transposase-accessible chromatin with sequencing) with single-cell data has elucidated novel post-transcriptional regulatory layers in the developing ovary 8,9 . Lastly, larger-scale analyses involving multiple species demonstrate human-specific aspects of gonadal development; for example, the observation that expression of KLF4, ELF3, and ZNF581 is highly specific to the human germ cell specification programme 9 .…”

Section: Introductionmentioning

confidence: 99%

“…New technologies have facilitated further multi-modal -omic analyses; particularly, the integration of single cell ATAC-sequencing (assay for transposase-accessible chromatin with sequencing) with single-cell data has elucidated novel post-transcriptional regulatory layers in the developing ovary 8,9 . Lastly, larger-scale analyses involving multiple species demonstrate human-specific aspects of gonadal development; for example, the observation that expression of KLF4, ELF3, and ZNF581 is highly specific to the human germ cell specification programme 9 . These findings highlight the potential limitations of applying animal RNA-seq data to humans and the importance of studying human gonadal tissue where possible.…”

Section: Introductionmentioning

confidence: 99%

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Mapping the anatomical and transcriptional landscape of early human fetal ovary development

McGlacken-Byrne,

del Valle,

Xenakis

et al. 2023

Preprint

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The complex genetic mechanisms underlying human ovary development can give rise to clinical phenotypes if disrupted, such as Primary Ovarian Insufficiency and Differences of Sex Development. Through a clinically-focused lens, we combine single-nuclei RNA sequencing, bulk RNA sequencing, and micro-focus computed tomography to elucidate the anatomy and transcriptional landscape of the human fetal ovary across key developmental timepoints (Carnegie Stage 22 until 20 weeks post conception). We show the marked growth and distinct morphological changes within the fetal ovary at the critical timepoint of germ cell expansion, and demonstrate that the fetal ovary becomes more transcriptomically distinct from the testis with age. We describe novel ovary developmental pathways, relating to neuroendocrine signalling, energy homeostasis, mitochondrial networks, piRNA processes, and inflammasome regulation. We define transcriptional regulators and candidate genes for meiosis within the developing ovary. Together, this work advances our fundamental understanding of human ovary development and clinical ovarian insufficiency phenotypes.

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Beyond defence: Immune architects of ovarian health and disease

Bazzano,

Köninger,

Solano

2024

Semin Immunopathol

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Throughout the individual’s reproductive period of life the ovary undergoes continues changes, including cyclic processes of cell death, tissue regeneration, proliferation, and vascularization. Tissue-resident leucocytes particularly macrophages, play a crucial role in shaping ovarian function and maintaining homeostasis. Macrophages crucially promote angiogenesis in the follicles and corpora lutea, thereby supporting steroidogenesis. Recent research on macrophage origins and early tissue seeding has unveiled significant insights into their role in early organogenesis, e.g. in the testis. Here, we review evidence about the prenatal ovarian seeding of leucocytes, primarily macrophages with angiogenic profiles, and its connection to gametogenesis. In the prenatal ovary, germ cells proliferate, form cysts, and undergo changes that, following waves of apoptosis, give rice to the oocytes contained in primordial follicles. These follicles constitute the ovarian reserve that lasts throughout the female’s reproductive life. Simultaneously, yolk-sac-derived primitive macrophages colonizing the early ovary are gradually replaced or outnumbered by monocyte-derived fetal macrophages. However, the cues indicating how macrophage colonization and follicle assembly are related are elusive. Macrophages may contribute to organogenesis by promoting early vasculogenesis. Whether macrophages contribute to ovarian lymphangiogenesis or innervation is still unknown. Ovarian organogenesis and gametogenesis are vulnerable to prenatal insults, potentially programming dysfunction in later life, as observed in polycystic ovary syndrome. Experimental and, more sparsely, epidemiological evidence suggest that adverse stimuli during pregnancy can program defective folliculogenesis or a diminished follicle reserve in the offspring. While the ovary is highly sensitive to inflammation, the involvement of local immune responses in programming ovarian health and disease remains to be thoroughly investigated.

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Integration of single-cell transcriptome and chromatin accessibility of early gonads development among goats, pigs, macaques, and humans

Cited by 17 publications

References 65 publications

SMARTdb: An Integrated Database for Exploring Single-cell Multi-omics Data of Reproductive Medicine

SMARTdb: An Integrated Database for Exploring Single-cell Multi-omics Data of Reproductive Medicine

Mapping the anatomical and transcriptional landscape of early human fetal ovary development

Beyond defence: Immune architects of ovarian health and disease

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