Biology subjects

Dang, Y.

Publications and source records attributed to Dang, Y..

At least 37 records · Page 2Linked to original sources

bioRxiv2023

Von Willebrand Factor Synergizes with Tumor-Derived Extracellular Vesicles to Promote Gastric Cancer Metastasis

Cells of gastric cancer invade local tissue extensively and also metastasize through the circulation to remote organs. Patients with metastasized gastric cancer have poor outcomes. Cancer cells are known to release extracellular vesicles (EVs) that contribute to cancer progression, but how cancer cell-derived EVs promote cancer growth and metastasis remains poorly understood. We have recently reported that levels of circulating gastric cancer cell-derived EVs (gcEVs) and the adhesive ligand von Willebrand factor (VWF) are associated with cancer metastasis and poor prognosis of patients, but the underlying mechanism of this gcEV-VWF interaction was not known. Here we report results from a study designed to investigate the synergistic action of VWF and gcEVs in vitro and in mouse models. We showed that VWF in cancer-bearing mice was hyperadhesive and became microvesicle-bound. EV-bound VWF mediated the adhesion of gcEVs to the endothelium to disrupt endothelial integrity and facilitate the transendothelial migration of cancer cells and pulmonary metastasis. Reducing VWF adhesive activity by the metalloprotease ADAMTS-13 or promoting gcEV clearance by the scavenging factor lactadherin prevented pulmonary metastasis in mice. These results highlight the synergistic action of gcEVs and VWF in promoting gastric cancer metastasis and identifying new targets for its prevention. Key point: Author contributionsO_LIHyperadhesive VWF becomes microvesicle-bound to induce endothelial leakage and promote the pulmonary metastasis of gastric cancer in mice. C_LIO_LIReducing VWF activity by ADAMTS-13 and accelerating microvesicle clearance by lactadherin reduces pulmonary metastasis of gastric cancer. C_LI

cancer biology↗

bioRxiv2023

Self-propagating wave drives noncanonical antidurotaxis of skull bones in vivo

Cell motility is a key feature of tissue morphogenesis, and it is thought to be driven primarily by the active migration of individual cells or collectives. However, this model is unlikely to apply to cells lacking overt cytoskeletal, stable cell-cell or cell-cell adhesions, and molecular polarity, such as mesenchymal cells. Here, by combining a novel imaging pipeline with biophysical modeling, we discover that during skull morphogenesis, a self-generated collagen gradient expands a population of osteoblasts towards a softer matrix. Biomechanical measurements revealed a gradient of stiffness and collagen along which cells move and divide. The moving cells generate an osteogenic front that travels faster than individual tracked cells, indicating that expansion is also driven by cell differentiation. Through biophysical modeling and perturbation experiments, we found that mechanical feedback between stiffness and cell fate drives bone expansion and controls bone size. Our work provides a mechanism for coordinated motion that does not rely upon the cytoskeletal dynamics of cell migration. We term this self-propagating motion down a stiffness gradient, noncanonical antidurotaxis. Identification of alternative mechanisms of cellular motion will help in understanding how directed cellular motility arises in complex environments with inhomogeneous material properties.

biophysics↗

bioRxiv2023

The involvement of the human prefrontal cortex in the emergence of visual awareness

Exploring the neural mechanisms of awareness is a fundamental task of cognitive neuroscience. There is an ongoing dispute regarding the role of the prefrontal cortex (PFC) in the emergence of awareness, which is partially raised by the confound between report- and awareness-related activity. To address this problem, we designed a visual awareness task that can minimize report-related motor confounding. Our results show that saccadic latency is significantly shorter in the aware trials than in the unaware trials. Local field potential (LFP) data from 6 patients consistently show early (200-300 ms) awareness-related activity in the PFC, including event-related potential and high-gamma activity. Moreover, the awareness state can be reliably decoded by the neural activity in the PFC since the early stage, and the neural pattern is dynamically changed rather than being stable during the representation of awareness. Furthermore, the enhancement of dynamic functional connectivity, through the phase modulation at low frequency, between the PFC and other brain regions in the early stage of the awareness trials may explain the mechanism of conscious access. These results indicate that the PFC is critically involved in the emergence of awareness.

neuroscience↗

bioRxiv2022

Molecular mechanism of substrate recognition by folate transporter SLC19A1

Folate (vitamin B9) is the coenzyme involved in one-carbon transfer biochemical reactions essential for cell survival and proliferation, with its inadequacy causing developmental defects or severe diseases. Notably, mammalian cells lack the ability to de novo synthesize folate but instead rely on its intake from extracellular sources via specific transporters or receptors, among which SLC19A1 is the ubiquitously expressed one in tissues. However, the mechanism of substrate recognition by SLC19A1 has been unclear. Here we report the cryo-EM structures of human SLC19A1 and its complex with 5-methyltetrahydrofolate at 3.5-3.6 [A] resolution and elucidate the critical residues for substrate recognition. In particular, we reveal that two variant residues among SLC19 subfamily members would designate the specificity for folate. Moreover, we identify intracellular thiamine pyrophosphate as the favorite coupled substrate for folate transport by SLC19A1. Together, this work has established the molecular basis of substrate recognition by this central folate transporter.

biochemistry↗

bioRxiv2022

Life-course social disparities in body mass index trajectories across adulthood: cohort study evidence from China Health and Nutrition Survey

BackgroundThe social disparities in obesity may originate in early life and adult social class. There are various developmental trajectories of overweight/obesity in adulthood. It is unclear how the intergenerational mobility of socioeconomic status influences adult overweight/obesity in China. MethodsWe used longitudinal data from ten waves of the China Health and Nutrition Survey (CHNS) between 1989 and 2015 for our analysis. The group-based trajectory modeling was used to identify BMI trajectories in adulthood. Multinomial logistic regression was adopted to assess the associations between SES and adult BMI trajectories. ResultsAmong a total of 3,138 participants, three latent clusters, including normal-stable BMI (51.4%), progressive overweight group (39.8%), and progressive obesity group (8.8%), were identified. High fathers occupational position, high participants occupation position and educational attainment, respectively, were associated with greater obesity risk. Compared to a stable low life course SES trajectory, a stable high life course SES trajectory was associated with a 2.35-fold risk of obesity, and upward and downward social mobility trajectories increased the risk for overweight/obesity. Individuals in the highest relative to the lowest life course cumulative socioeconomic score group had around twice risk of obesity. ConclusionsThe results emphasize the role of the high SES in early life and life-course SES accumulation, in the obesity intervention in China. FundingAll the work was supported by the National Natural Science Foundation of China (Grant Nos. 72174167, 81602928) and Natural Science Foundation of Shaanxi (2021JM-031).

scientific communication and education↗

bioRxiv2022

Transcriptomic analysis reveals hub genes and pathways in response to acetic acid stress in Kluyveromyces marxianus during high-temperature ethanol fermentation

The thermotolerant yeast Kluyveromyces marxianus has great potential for high-temperature ethanol fermentation, but it produces excess acetic acid during high-temperature fermentation, which inhibits ethanol production. The mechanisms of K. marxianuss responses to acetic acid have not been fully understood. In this study, the transcriptomic changes of K. marxianus DMKU3-1042 resulted from acetic acid stress during high-temperature ethanol fermentation were investigated based on high-throughput RNA sequencing. We identified 611 differentially expressed genes (DEGs) under acetic acid stress (fold change > 2 or < 0.5, P-adjust <0.05), with 166 up-regulated and 445 down-regulated. GO terms and pathways enriched in these DEGs were identified. Protein-protein interaction (PPI) networks were constructed based on the interactions between proteins coded by the DEGs, and hub genes and key modules in the PPI networks were identified. The results in this study indicated that during high-temperature fermentation, acetic acid stress promoted protein catabolism but repressed protein synthesis, which affected the growth and metabolism of K. marxianus and led to the decrease of ethanol production. The findings in this study provide a better understanding of the response mechanism of K. marxianus to acetic acid stress, and provide a basis for subsequent increase of ethanol production by K. marxianus.

microbiology↗

bioRxiv2021

Linker histone H1FOO is required for bovine preimplantation development by regulating lineage specification and nucleosome assembly

Linker histone H1 binds to the nucleosome and is implicated in the regulation of the chromatin structure and function. The H1 variant H1FOO is heavily expressed in oocytes and early embryos. However, given the poor homology of H1FOO among mammals, the functional role of H1FOO during early embryonic development remains largely unknown, especially in domestic animals. Here, we find that H1FOO is not only expressed in oocytes and early embryos but granulosa cells and spermatids in cattle. We then demonstrate that the interference of H1FOO results in early embryonic developmental arrest in cattle using either RNA editing or Trim-Away approach. H1FOO depletion leads to compromised expression of critical lineage-specific genes at the morula stage and affects the establishment of cell polarity. Interestingly, H1FOO depletion causes a significant increase in expression genes encoding other linker H1 and core histones. Concurrently, there is an increase of H3K9me3 and H3K27me3, two markers of repressive chromatin and a decrease of H4K16ac, a marker of open chromatin. Importantly, overexpression of bovine H1FOO results in severe embryonic developmental defects. In sum, we propose that H1FOO controls the proper chromatin structure that is crucial for the fidelity of cell polarization and lineage specification during bovine early development.

developmental biology↗

bioRxiv2021

Genome-wide mapping of histone modification H3K4me3 in bovine oocytes and early embryos

Reprogramming of histone modifications is critical to safeguard correct gene expression profile during preimplantation development. Of interest, trimethylation of lysine 4 on histone 3 (H3K4me3) exhibits a unique and dynamic landscape with a potential species-specific feature. Here, we address how it is reprogrammed and its functional significance during oocyte maturation and early embryonic development in cows. Notably, the overall signal of H3K4me3 decreased sharply during embryonic genome activation (EGA). By using low input ChIP-seq technology, we find widespread broad H3K4me3 domains in oocytes and early cleaved embryos. The broad domains are gradually removed after fertilization, which is obviously seen during EGA. Meanwhile, H3K4me3 become enriched at promoter regions. Interestingly, the gene expression level displays a positive correlation with the relative H3K4me3 signal of their promoters when embryos reach 16-cell stage. Importantly, disruption of H3K4me3 demethylases KDM5A-5C increases H3K4me3 level, decreases the embryonic developmental rate and results in dysregulation of over a thousand genes. Meanwhile, KDM5 deficiency causes a re-destribution of H3K4me3 across genome. In particular, the positive correlation between promoter H3K4me3 enrichment and gene expression level disappear. Overall, we describe the genomic reprogramming of H3K4me3 in a greater resolution during bovine preimplantation development and propose that KDM5-mediated re-distribution of H3K4me3 plays an important role in modulating oocyte-to-embryonic transition.

developmental biology↗

bioRxiv2021

Base editing in bovine embryos reveals a species-specific role of SOX2 in regulation of pluripotency

The emergence of the first three lineages during development are orchestrated by a network of transcription factors, which are best characterized in mice. However, the role and regulation of these factors are not completely conserved in other mammals, including human and cattle. Here, we establish a gene inactivation system by introducing premature codon with cytosine base editor in bovine embryos with a robust efficiency. Of interest, SOX2 is universally localized in early blastocysts but gradually restricted into the inner cell mass in cattle. SOX2 knockout results in a failure of the establishment of pluripotency. Indeed, OCT4 level is significantly reduced and NANOG was barely detectable. Furthermore, the formation of primitive endoderm is compromised with few SOX17 positive cells. Single embryo RNA-seq reveals a dysregulation of 2074 genes, among which 90% are up-regulated in SOX2-null blastocysts. Intriguingly, more than a dozen lineage-specific genes, including OCT4 and NANOG, are down-regulated. Moreover, SOX2 expression is sustained in the trophectoderm in absence of CDX2 in bovine late blastocysts. Overall, we propose that SOX2 is dispensable for OCT4 and NANOG expression and disappearance of SOX2 in the trophectoderm depends on CDX2 in cattle, which are all in sharp contrast with results in mice. SignificanceThe first and second cell fate decisions of a new life are important for subsequent embryonic and plancental development. These events are finely controlled by a network of transcriptional factors, which are extensively characterized in mice. Species-specific roles of these proteins are emerging in mammals. Here, we develop a gene loss-of-function system by using cytosine base editors in bovine embryos. We find that expression pattern, functional roles, and regulation of SOX2 are all different between mouse and bovine embryos. Remarkbly, SOX2 is required for OCT4 and NANOG, two well established pluripoteny genes. Furthermore, CDX2 is required to shut down SOX2 in the trophectoderm. Given similar expression pattern of SOX2 between human and bovine blastocysts, bovine embryos represents a putative model to investigate human pluripotency regulation in vivo.

developmental biology↗

bioRxiv2021

The histone deacetylase activity of HDAC1/2 is required to safeguard zygotic genome activation in mice and cattle

The genome is transcriptionally inert at fertilization and must be activated through a remarkable developmental process called zygotic genome activation (ZGA). The gene expression pattern formed over the course of ZGA is required for establishing totipotency in early embryos and subsequent development. Substantial epigenetic reprogramming contributes significantly to the pronounced change in gene expression during ZGA, however the mechanism has yet to be resolved. Here, we find histone deacetylase 1 and 2 (HDAC1/2) are critical histone modifiers that regulate ZGA through the histone deacetylase activity. Notably, we show that H3K27ac level declines dramatically during ZGA with a dynamic change in its genome-wide distribution. In mouse embryos, ectopic expression of HDAC1/2 dominant negative mutant leads to a failure of H3K27ac removal and a developmental arrest at 2-cell stage. RNA-seq results reveal a remarkable transcriptomic change with 6565 differentially expressed genes identified. Further analysis shows 64% of down-regulated genes are ZGA genes and 49% of up-regulated genes are developmental genes. Low input ChIP-seq analysis exhibits an increase and decrease of H3K27ac enrichment at the promoter region of up- and down-regulated genes, respectively. Moreover, HDAC1 mutants prohibited removal of broad H3K4me3 domain via impeding the expression of Kdm5s during ZGA. Importantly, the developmental block can be greatly overcome through injection of Kdm5b mRNA and expression of the majority of dysregulated genes partially corrected. Similar functional significance of HDAC1/2 in ZGA is conserved in bovine embryos. Together, we propose that HDAC1/2 is indispensable for mouse and bovine ZGA via creating correct transcriptional repressive and active states.

developmental biology↗

bioRxiv2021

Extrachromosomal DNA is associated with chromothripsis events and diverse prognoses in gastric cardia adenocarcinoma

Extrachromosomal DNA plays an important role in oncogene amplification in tumour cells and poor outcomes across multiple cancers. However, the function of extrachromosomal DNA in gastric cardia adenocarcinoma (GCA) is very limited. Here, we investigated the availability and function of extrachromosomal DNA in GCA from a Chinese cohort of GCA using whole-genome sequencing (WGS), whole-exome sequencing (WES), and immunohistochemistry. For the first time, we identified the ecDNA amplicons present in most GCA patients, and found that some oncogenes are present as ecDNA amplicons in these patients. We found that oncogene ecDNA amplicons in the GCA cohort were associated with the chromothripsis process and may be induced by accumulated DNA damage due to local dietary habits in the geographic region. Strikingly, we observed diverse correlations between the presence of ecDNA oncogene amplicons and prognosis, where ERBB2 ecDNA amplicons correlated with good prognosis, EGFR ecDNA amplicons correlated with poor prognosis, and CCNE1 ecDNA amplicons did not correlate with prognosis. Large-scale ERBB2 immunohistochemistry results from 1668 GCA patients revealed that there was a positive correlation between the presence of ERBB2 and prognosis in 2-7-year survival; however, there was a negative correlation between the presence of ERBB2 and prognosis in 0-2-year survival. Our observations indicate that the presence of ERBB2 ecDNA in GCA patients may represent a good prognosis marker.

genomics↗

bioRxiv2021

Sustained Oxygenation Accelerates Diabetic Wound Healing by Simultaneously Promoting Epithelialization and Angiogenesis, and Decreasing Tissue Inflammation

Non-healing diabetic wound is one of the most common complications for diabetic patients. Chronic hypoxia is among the prominent factors that delay the wound healing process. Therefore, sustained oxygenation to alleviate hypoxia is hypothesized to promote diabetic wound healing. Yet it cannot be achieved by current clinical approaches including hyperbaric oxygen therapy. Herein, we developed a sustained oxygenation system consisting of oxygen-release microspheres and a reactive oxygen species (ROS)-scavenging hydrogel. The hydrogel was used to capture the ROS that is elevated in the diabetic wounds, and that may be generated due to oxygen release. The sustainedly released oxygen augmented survival and migration of keratinocytes and dermal fibroblasts; promoted angiogenic growth factor expression, and angiogenesis in the diabetic wounds; and decreased M1 macrophage density. These effects led to a significant increase of wound closure rate. These findings reveal that sustained oxygenation alone without using drugs is capable of healing diabetic wounds.

bioengineering↗

bioRxiv2020

The C. elegans homolog of TMEM132D, a human panic-disorder and anxiety risk gene, modulates neuronal morphogenesis through the WAVE-regulatory complex

TMEM132D is a human gene identified with multiple risk alleles for panic disorders, anxiety and major depressive disorders. Belonging to a conserved family of transmembrane proteins, TMEM132D and its homologs are still of unknown molecular functions. By generating loss-of-function mutants of the sole TMEM132 ortholog in C. elegans, we identify abnormal morphologic phenotypes in the dopaminergic PDE neurons. Using a yeast two-hybrid screen, we find that NAP1 directly interacts with the cytoplasmic domain of human TMEM132D, and mutations in C. elegans tmem-132 that disrupt the interaction with NAP1 cause similar morphologic defects in the PDE neurons. NAP1 is a component of the WAVE regulatory complex (WRC) that controls F-actin cytoskeletal dynamics. Decreasing activity of WRC rescues the PDE defects in tmem-132 mutants, whereas gain-of-function of TMEM132D in mammalian cells inhibits WRC, leading to decreased abundance of selective WRC components, impaired actin nucleation and cell motility. We propose that metazoan TMEM132 family proteins play evolutionarily conserved roles in regulating NAP1 protein homologs to restrict inappropriate WRC activity, cytoskeletal and morphologic changes in the cell.

genetics↗

bioRxiv2020

Ripasudil in a model of pigmentary glaucoma

PurposeTo investigate the effects of Ripasudil (K-115), a Rho-kinase inhibitor, in a porcine model of pigmentary glaucoma. MethodsHallmark features of trabecular meshwork (TM), the principle structure of the outflow system affected in this model, were analyzed. In vitro TM cells and ex vivo perfused eyes were subjected to pigment dispersion followed by K-115 treatment (PK115). PK115 was compared to sham-treated controls (C) and pigment (P). Cytoskeletal alterations were assessed by F-actin labeling. TM cell phagocytosis of fluorescent targets was evaluated by flow cytometry. Cell migration was studied with a wound-healing assay. Intraocular pressure was continuously monitored and compared to after the establishment of the pigmentary glaucoma model and after treatment with K-115. ResultsIn vitro, the percentage of cells with stress fibers increased in response to pigment but declined sharply after treatment with K-115 (P: 32.8 +/- 2.9%; PK115: 11.6 +/- 3.3%, P < 0.001). Phagocytosis first declined but recovered after K-115 (P: 25.7+/-2.1%, PK115: 33.4+/-0.8%, P <0.01). Migration recuperated at 12h with K-115 treatment (P: 19.1+/-4.6 cells/high-power field, PK115: 42.5+/-1.6 cells/high-power field, P <0.001). Ex vivo, eyes became hypertensive from pigment dispersion but were normotensive after treatment with K-115 (P: 20.3 +/- 1.2 mmHg, PK115: 8.9 +/- 1.7 mmHg; P< 0.005). ConclusionIn vitro, K-115 reduced TM stress fibers, restored phagocytosis, and restored migration of TM cells. Ex vivo, K-115 normalized intraocular pressure.

pharmacology and toxicology↗

bioRxiv2019

Cellular dialogues that enable self-organization of dynamic spatial patterns

Cells form spatial patterns by coordinating their gene expressions. How a group of mesoscopic numbers (hundreds-to-thousands) of cells, without pre-defined morphogens and spatial organization, self-organizes spatial patterns remains incompletely understood. Of particular importance are dynamic spatial patterns - such as spiral waves that perpetually move and transmit information over macroscopic length-scales. We developed an open-source, expandable software that can simulate a field of cells communicating with any number of cell-secreted molecules in any manner. With it and a theory developed here, we identified all possible \"cellular dialogues\" - ways of communicating with two diffusing molecules - and core architectures underlying them that enable diverse, self-organized dynamic spatial patterns that we classified. The patterns form despite widely varying cellular response to the molecules, gene-expression noise, and spatial arrangement and motility of cells. Three-stage, \"order-fluctuate-settle\" process forms dynamic spatial patterns: cells form long-lived whirlpools of wavelets that, through chaos-like interactions, settle into a dynamic spatial pattern. These results provide a blueprint to help identify missing regulatory links for observed dynamic-pattern formations and in building synthetic tissues.

systems biology↗

bioRxiv2019

Essential roles of Hdac1 and 2 in lineage development and genome-wide DNA methylation during mouse preimplantation development

Epigenetic modifications, including DNA methylation and histone modifications, are reprogrammed considerably following fertilization during mammalian early embryonic development. Incomplete epigenetic reprogramming is a major factor leading to poor developmental outcome in embryos generated by assisted reproductive technologies, such as somatic cell nuclear transfer. However, the role of histone modifications in preimplantation development is poorly understood. Here, we show that co-knockdown (cKD) of Hdac1 and 2 (but not individually) resulted in developmental failure during the morula to blastocyst transition. This outcome was also confirmed with the use of small-molecule Hdac1/2-specific inhibitor FK228. We observed reduced cell proliferation and increased incidence of apoptosis in cKD embryos, which were likely caused by increased acetylation of Trp53. Importantly, both RNA-seq and immunostaining analysis revealed a failure of lineage specification to generate trophectoderm and pluripotent cells. Among many gene expression changes, a substantial decrease of Cdx2 may be partly accounted for by the aberrant Hippo pathway occurring in cKD embryos. In addition, we observed an increase in global DNA methylation, consistent with increased DNA methyltransferases and Uhrf1. Interestingly, deficiency of Rbbp4 and 7 (both are core components of several Hdac1/2-containing epigenetic complexes) results in similar phenotypes as those of cKD embryos. Overall, Hdac1 and 2 play redundant functions required for lineage specification, cell viability and accurate global DNA methylation, each contributing to critical developmental programs safeguarding a successful preimplantation development.\n\nSignificanceSubstantial changes to epigenetic modifications occur during preimplantation development and can be detrimental when reprogrammed incompletely. However, little is known about the role of histone modifications in early development. Co-knockdown of Hdac1 and 2, but not individually, resulted in developmental arrest during morula to blastocyst transition, which was accompanied by reduced cell number per embryo and increased incidence of apoptosis. Additionally, we observed a failure of first lineage specification to generate trophectoderm and pluripotent cells, which were associated with reduced expression of key lineage-specific genes and aberrant Hippo pathway. Moreover, an increase in global DNA methylation was found with upregulated Dnmts and Uhrf1. Thus, Hdac1 and 2 play overlapping roles in lineage development, apoptosis, and global methylation during preimplantation development.

developmental biology↗

bioRxiv2018

Onset of differentiation is posttranscriptionally controlled in adult neural stem cells

The contribution of posttranscriptional regulation of gene expression to neural stem cell differentiation during tissue homeostasis remains elusive. Here we show highly dynamic changes in protein synthesis along differentiation of stem cells to neurons in vivo. Examination of individual transcripts using RiboTag mouse models reveals that neural stem cells efficiently translate abundant transcripts, whereas translation becomes increasingly controlled with the onset of differentiation. Stem cell generation of early neuroblasts involves translational repression of a subset of mRNAs including the stem cell-identity factors Sox2 and Pax6 as well as translation machinery components. In silico motif analysis identifies a pyrimidine-rich motif (PRM) in this repressed subset. A drop in mTORC1 activity at the onset of differentiation selectively blocks translation of PRM-containing transcripts. Our data uncovers how a drop in mTORC1 allows robust simultaneous posttranscriptional repression of key stem cell identity-factors and translation-components and thereby stemness exit and migration.

neuroscience↗

bioRxiv2018

Transcriptome Landscape of Human Oocytes and Granulosa Cells Throughout Folliculogenesis

Folliculogenesis is a highly regulated process that involves bidirectional interactions of the oocytes and surrounding granulosa cells (GCs). Little is unknown, however, about the transcriptomic profiles of human oocytes and GCs throughout folliculogenesis. Here we performed a high resolution RNA-Seq of human oocytes and GCs at each follicular stage, which revealed unique transcriptional profiles, stage-specific signature genes, oocyte- and GC-derived genes that reflect ovarian reserve. We identified reciprocal cell-to-cell interactions between oocytes and GCs, including NOTCH, TGF-{beta} signaling and gap junctions and determined the expression patterns of maternal-effect genes involved in folliculogenesis and early embryogenesis. Finally, we demonstrated robust differences between human and mice oocyte transcriptomes. This is the first comprehensive overview of the transcriptomic signatures governing the stepwise human folliculogenesis in-vivo that provides a valuable resource for basic and translational research in human reproductive biology.

cell biology↗