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Yang, S.-H.

Publications and source records attributed to Yang, S.-H..

17 recordsLinked to original sources

Electrode pooling preserves movement decoding by retaining neural population dynamics

New implantable-electrode fabrication strategies make dense, ultrafine electrode arrays with lower tissue burden increasingly feasible, shifting a key bottleneck for scalable brain-computer interfaces from electrode placement to readout capacity. Electrode pooling, in which multiple electrodes share a readout channel, could relax this bottleneck by combining extracellular signals before acquisition, but it has remained unclear whether such compression preserves the neural population structure needed for behavioral decoding. Here we evaluate this question using software-emulated electrode pooling in mouse sensorimotor cortex during a cue-guided reach-and-grasp task using a high-density microwire array coupled to a CMOS microelectrode-array platform. Pooled recordings retain forelimb kinematic information more effectively than a channel-matched control that discards electrodes. Pooling reduces the separability of electrode-specific spikes and sorted units, indicating a loss of some neuronal detail, but the mixed signals still preserve task-aligned low-dimensional latent dynamics that support decoding. When readout capacity is fixed, this trade-off allows broader electrode coverage to contribute to behaviorally informative population sampling. Together, these results define electrode pooling as a design trade-off for scalable readout, in which some electrode-specific neuronal information is lost but the population dynamics needed for movement decoding remain accessible.

neuroscience↗

Small Molecule Activators of Protein Phosphatase 2A Exert Global Stabilising Effects on the Scaffold PR65

Protein phosphatase 2A (PP2A), an important therapeutic target, comprises a scaffold subunit PR65 composed of 15 HEAT (Huntingtin/elongation/A-subunit/TOR1) repeats, a catalytic subunit, and one of many different regulatory subunits that enable binding to specific substrates. Recently, small molecule activators of PP2A (SMAPs) were identified, although their mechanisms of action have not been fully defined. Here we explore the interaction of PR65 with two SMAPs, ATUX-8385 and the non-functional DBK-776, using single-molecule optical tweezers, ensemble methods, and computational analysis. In the absence of SMAP, PR65 shows multiple unfolding and refolding transitions, and the force-extension profiles are very heterogeneous with evidence of misfolding. Similar heterogeneity has been observed for chemical-induced unfolding of tandem-repeat proteins like PR65, a consequence of the internal symmetry of the repeat architecture. In the presence of ATUX-8385, higher unfolding and refolding forces are observed globally, and there is less misfolding, suggesting that ATUX-8385 acts like a pharmacological chaperone. In contrast, DBK-766-binding induces higher unfolding forces for only a few repeats of PR65, suggestive of a more localised effect; moreover, subsequent stretch-relax cycles show that PR65 is irreversibly locked in the unfolded state. Docking and molecular dynamics simulations provide additional insights how SMAP binding modulates PR65 structure and function.

biophysics↗

Superficial stromal cell population in the mouse uterus require METTL14 for development and functional competence to support embryo implantation

Uterine stromal cells are critical for pregnancy, coordinating embryo implantation, placental development, and maintenance of gestation. Single-cell RNA-seq analyses have identified two distinct stromal cell populations in the mouse uterus: superficial and deep stromal cells. However, their functional specialization remains unresolved. Here, we show that mice lacking methyltransferase-like 14 (METTL14), a core enzyme of the m6A methyltransferase complex, exhibit a selective depletion of superficial stromal cells while preserving deep stromal cells. This genetic model allowed us to investigate the physiological role of superficial stromal cells in uterine function. Paralleled by the aberrant development and loss of superficial stromal cells, Mettl14 deletion impaired embryo implantation and decidualization. Transcriptomic profiling revealed that Mettl14 deficiency disrupts hormonal signaling by upregulating estrogen (E2)-responsive genes and downregulating progesterone (P4)-responsive genes, resulting in aberrant development and loss of superficial stromal cells. Mechanistically, Mettl14 ablation reduces m6A methylation in the 3'-UTR of Esr1 mRNA, thereby impairing m6A-dependent mRNA degradation and elevating ESR1 expression, which amplifies E2 signaling. This study underscores the essential role of METTL14 in maintaining the superficial stromal cell population required for embryo implantation by regulating Esr1 mRNA stability through m6A modification.

physiology↗

Programmed downregulation of METTL3 is essential for decidualization in both humans and mice

N6-methyladenosine (m6A), the most abundant mRNA modification in eukaryotes, plays an essential role in regulating gene expression. Our prior research, alongside that of others, demonstrated that conditional uterine knockout of methyltransferase-like 3 (METTL3), the enzyme responsible for m6A modification, led to complete failure of embryo implantation and decidualization. Intriguingly, METTL3 expression is downregulated rather than upregulated in human endometrial stromal cells (HESCs) during in vitro decidualization and in mouse decidual tissues during pregnancy. We hypothesized that this decline in METTL3 expression is indispensable for successful decidualization. To test this hypothesis, we overexpressed METTL3 in HESCs and observed impaired decidualization in vitro. Additionally, we generated genetically engineered mice with uterine-specific METTL3 overexpression using Pgr-Cre, which exhibited subfertility mainly due to impaired decidualization. Further investigation revealed a marked decrease in HAND2, a well-established regulator of decidualization, following METTL3 overexpression. Mechanistically, we uncovered that METTL3 destabilizes HAND2 mRNA via m6A modification at the 5'-UTR. In summary, our study underscores the critical role of programmed METTL3 downregulation in decidualization by sustaining HAND2 expression.

physiology↗

CTCF is crucial for decidualization of uterine stromal cells through facilitating HOXA11 expression

CCCTC-binding factor (CTCF), a highly versatile transcriptional regulator and chromatin architectural protein, plays a pivotal role in mammalian development. In this study, we investigated the function of CTCF in uterine biology during pregnancy. We observed that CTCF expression in the human endometrium decreases from the proliferative to the secretory phase of the menstrual cycle. Similarly, in cultured human endometrial stromal cells (hESCs), CTCF expression declines during in vitro decidualization. Using siRNA-mediated knockdown, we demonstrated that CTCF is essential for the early phase of decidualization but dispensable in later stages. Notably, CTCF depletion reduces the expression of HOXA11, a well-established regulator of decidualization, and overexpression of HOXA11 rescues the decidualization defects caused by CTCF loss, identifying HOXA11 as a key downstream effector of CTCF. Mechanistically, CTCF binds to the HOXA11 promoter to facilitate its transcriptional activation. Furthermore, uterine-specific knockout of CTCF in Pgr-Cre mice leads to female infertility, characterized by diminished HOXA11 expression, impaired uterine receptivity, and defective decidualization. Collectively, our findings highlight the critical role of the CTCF-HOXA11 axis in decidualization in both humans and mice, providing novel insights into the molecular regulation of this process and potential therapeutic targets for reproductive disorders.

physiology↗

NAT10 governs uterine function and fertility by stabilizing progesterone receptor mRNA via ac4C modification

The N4-acetylcytidine (ac4C) modification is one of the most abundant chemical modifications in mammalian transcriptome, which plays a crucial role in regulating gene expression across various biological processes. In this study, we investigate the role of N4-acetyltransferase 10 (NAT10), the sole enzyme responsible for catalyzing the ac4C modification, in uterine function. Our findings revealed that knockdown of NAT10 in cultured human endometrial stromal cells leads to decreased progesterone receptor (PGR) expression and compromised decidualization. Mechanistically, NAT10 is found to enhance the stability of PGR mRNA through its ac4C modification in the coding sequence (CDS). Furthermore, conditional deletion of Nat10 in the mouse uterus using Pgr-Cre resulted in defective pubertal uterine development, characterized by a thinner stroma and reduced endometrial gland number. These mice were infertile in adulthood, experiencing failures in both implantation and decidualization. However, heterozygous Nat10 conditional knockout mice showed reduced NAT10 expression in the uterus without affecting uterine development or fertility. To bridge the gap between heterozygous and homozygous knockout conditions, we employed Remodelin, an inhibitor of NAT10, in adult female mice, to mimic an intermediate gene dosage. Our results demonstrated that inhibiting NAT10 with Remodelin preserved uterine structures but disrupted the PGR signaling pathway, leading to impaired uterine function during pregnancy. In conclusion, our study provides compelling evidence that NAT10 safeguards uterine function and fertility by regulating the ac4C modification of PGR mRNA. SignificanceHere we identified NAT10-catalyzed ac4C modification of progesterone receptor (PGR) mRNA as a crucial mechanism regulating PGR expression by enhancing its mRNA stability. In vitro studies using human endometrial stromal cells show that the NAT10-PGR axis is required for decidualization. Additionally, genetic and pharmacologic manipulations in mice further demonstrate the necessity of NAT10-dependent P4/PGR signaling for uterine function during implantation and decidualization. Our findings highlight the importance of NAT10-mediated ac4C modification in maintaining PGR expression and uterine function.

physiology↗

Salinity impacted microbial carbonate precipitation mechanisms of modern microbialites in peritidal zone

Microbialites, ancient records of microbial activity, serve as significant indicators of environmental change. This study examined microbialites from the peritidal zone of three tide pools at Fongchueisha, Hengchun, Taiwan, to investigate the impact of salinity on microbial community composition and carbonate precipitation mechanisms. Microbial samples were collected across varying salinity gradients over multiple timepoints and analyzed using next-generation sequencing of bacterial 16S and eukaryotic 18S rRNA genes. Our findings reveal that the microbial communities in higher salinity environments exhibited significant shifts, with increased relative abundance of ureolytic bacteria and ammonifying microorganisms, such as Myxococcota and Actinobacteriota. This suggests the presence of diverse microbial carbonate precipitation mechanisms beyond photosynthesis, including ureolysis and ammonification. Furthermore, our results show that changes in the composition of cyanobacteria and diatoms were influenced by salinity, with heterocystous cyanobacteria (e.g., Nostocales) dominating low-salinity environments, and non-heterocystous cyanobacteria (e.g., Synechococcales) prevailing in higher salinity environments. Functional predictions reveal that microbial communities in high-salinity environments were enriched in anaerobic metabolic pathways, including pyruvate fermentation and the urea cycle. These findings highlight the significant role of salinity in influencing microbial composition and metabolic pathways, shaping carbonate precipitation processes in microbialites. ImportanceThe study focuses on the impact of environmental salinity on microbial community composition and carbonate precipitation mechanisms within modern microbialites, based on an analysis of samples from three tide pools with different salinity levels collected at five time points throughout the year. Using next-generation sequencing of bacterial 16S and eukaryotic 18S rRNA genes, we identified key shifts in microbial communities along salinity gradients and explored diverse microbial processes involved in carbonate precipitation. This work enhances our understanding of microbial ecosystems within modern microbialites and their response to environmental changes. Additionally, our study provides insight into ancient biogeochemical processes, with implications for interpreting microbial metabolism in carbonate precipitation across different salinity regimes.

microbiology↗

Successive responses of three coral holobiont components (coral hosts, symbiotic algae, and bacteria) to daily temperature fluctuations

Coral reef ecosystems support over a quarter of the worlds marine life and play important ecological and economic roles. However, the increasingly severe weather events associated with ocean warming and climate change are believed to be rapidly altering the functions of coral reefs and their ecosystems. Corals and their associated microbiota form a "holobiont," which includes symbiotic algae and other associated microbiota dominated by bacteria. These microbiota have a direct relationship with the health of the coral host. Their composition is influenced by various environmental factors, such as increasing sea water temperatures. Previous studies of the effects of temperature changes on coral physiology and associated bacterial communities have been conducted based on stable water temperatures set by mean temperatures, or by slowly increasing/decreasing temperatures. However, the daily temperature fluctuations that corals experience in nature are not stable. Rather, there may be significant differences of up to 6{degrees}C in a single day. The current understanding of the effects of large daily temperature fluctuations on coral and associated bacterial community dynamics is limited. Hence, in this study, we conducted a four-week tank experiment using different large daily temperature fluctuations accompanied by continuous warming conditions to investigate the effects on two common reef-building corals, Stylophora pistillata and Pocillopora acuta, in Taiwan. During the experiment, the activity of coral host catalase was measured, the photosynthetic ability of symbiotic algae was recorded, and the variation in bacterial communities was analyzed using the V6-V8 region of 16S rDNA. According to the results, different parts of the holobionts of different coral species exhibited varying response rates to the continuous warming conditions and diurnal temperature fluctuations. Additionally, it was found that diurnal temperature fluctuations may mitigate the heat stress on the host and reduce the changes in bacterial response to warming. Furthermore, the holobionts of different coral species may adopt different adaptation and survival strategies in response to diurnal temperature fluctuations and warming. Finally, based on the response of these two coral species under the conditions of diurnal temperature fluctuations and continuous warming, Acinetobacter and Rhodobacteraceae were identified as potential indicator coral-associated bacteria. This is the first study to investigate the tripartite dynamic response of coral, symbiotic algae and bacteria to daily temperature fluctuations.

microbiology↗

eRNA profiling uncovers the enhancer landscape of oesophageal adenocarcinoma and reveals new deregulated pathways

Cancer is driven by both genetic and epigenetic changes that impact on gene expression profiles and the resulting tumourigenic phenotype. Enhancers are transcriptional regulatory elements that are key to our understanding of how this rewiring of gene expression is achieved in cancer cells. Here we have harnessed the power of RNA-seq data from hundreds of patients with oesophageal adenocarcinoma (OAC) or its precursor state Barretts oesophagus (BO) coupled with open chromatin maps to identify potential enhancer RNAs (eRNAs) and their associated enhancer regions in this cancer. We identify [~]1000 OAC-specific enhancers and use this data to uncover new cellular pathways that are operational in OAC. Among these are enhancers for JUP, MYBL2 and CCNE1, and we show that their activity is required for cancer cell viability. We also demonstrate the clinical utility of our dataset for identifying disease stage and patient prognosis. Our data therefore identify an important set of regulatory elements that enhance our molecular understanding of OAC and point to potential new therapeutic directions.

cancer biology↗

The soil microbiome may offer solutions to ginger cultivation

The Taitung region is one of Taiwans main places for ginger agriculture. Due to issues with disease and nutrient, farmers cannot use continuous cropping techniques on ginger, meaning that the ginger industry is constantly searching for new lands. Continuous cropping increases the risk of infection by Pythium myriotylum and Ralstonia solanacearum, which cause soft rot disease and bacterial wilt, respectively. In addition, fertilizer additives cannot recover the soil when using continuous cropping on ginger, even when there is no decrease in trace elements observed in the soil. Although there may be other reasons for the reduction in production, such as soil microbes, we know little about the soil microbiome associated with ginger cultivation. Hence, in this study, we used the bacterial 16S V3-V4 hypervariable region of the 16S ribosomal RNA region to investigate microbe compositions in ginger soil to identify the difference between ginger soil with and without disease. Later, to investigate the influence of the well-known biocontrol agent-B. velezensis and fungicide Etridiazole on soil microbes and ginger productivity, we designed an experiment that collected the soil samples according to the different ginger cultivation periods to examine the microbial community dynamics in the rhizome and bulk soil. We demonstrated that B. velezensis is beneficial to ginger reproduction and suggest that it may influence the plant by adjusting its soil microbial composition. Etridiazole, on the other hand, may have some side effects on the ginger or beneficial bacteria in the soils, inhibiting ginger reproduction.

microbiology↗

Genome Assembly and Population Resequencing Reveal the Geographical Divergence of 'Shanmei'(Rubus corchorifolius)

Rubus corchorifolius ( Shanmei or mountain berry, 2n =14) is widely distributed in China, and its fruit has high nutritional and medicinal values. Here, we report a high-quality chromosome-scale genome assembly of Shanmei, with a size of 215.69 Mb and encompassing 26,696 genes. Genome comparisons among Rosaceae species show that Shanmei and Fupenzi (Rubus chingii Hu) are most closely related, and then is blackberry (Rubus occidentalis). Further resequencing of 101 samples of Shanmei collected from four regions in provinces of Yunnan, Hunan, Jiangxi, and Sichuan in South China reveals that the Hunan population of Shanmei possesses the highest diversity and may represent the relatively more ancestral population. Moreover, the Yunnan population undergoes strong selection based on nucleotide diversity, linkage disequilibrium, and the historical effective population size analyses. Furthermore, genes from candidate genomic regions that show strong divergence are significantly enriched in flavonoid biosynthesis and plant hormone signal transduction, indicating the genetic basis of adaptation of Shanmei to the local environments. The high-quality genome sequences and the variome dataset of Shanmei provide valuable resources for breeding applications and for elucidating the genome evolution and ecological adaptation of Rubus species.

genomics↗

Exploration of molecular mechanism underlying the self-flocculation of Zymomonas mobilis through comparative omics analyses and experimental validations for developing robust production systems

Zymomonas mobilis metabolizes sugar through the Entner-Doudoroff pathway with less ATP generated for lower biomass accumulation and more substrate to product formation with improved yield, since ATP is dissipated predominately through growth for intracellular energy homeostasis, making it a platform to be engineered as microbial cell factories, particularly for producing bulk commodities with major cost from feedstock consumption. ZM401, a self-flocculating mutant, presents advantages for production including cost-effective biomass recovery through gravity sedimentation, self-immobilization within bioreactors for high cell density to improve productivity and enhanced tolerance to environmental stresses for high product titers, but molecular mechanism underlying this phenotype is largely unknown. In this work, we sequenced and assembled the genome of ZM401 to explore genetic basis for the self-flocculation of the bacterial cells through comparative genomic and transcriptomic analyses, molecular docking simulations for enzymes encoded by functional genes and their substrates/activators, and experimental validations. Our results demonstrated that the single nucleotide deletion in ZMO1082 disrupted its stop codon for the putative gene being fused with ZMO1083, which created an exciting gene encoding the subunit A of the bacterial cellulose synthase with unique function for synthesizing cellulose microfibrils to flocculate the bacterial cells, and the single nucleotide mutation in ZMO1055 compromised the function of bifunctional diguanylate cyclase/phosphodiesterase encoded by the gene on the degradation of c-di-GMP for its intracellular accumulation to activate the cellulose biosynthesis. These discoveries are significant not only for optimizing the self-flocculation of Z. mobilis, but also engineering other bacteria with the self-flocculating phenotype for robust production.

microbiology↗

Fibroblast growth factor 9 stimulates neurite outgrowth through NF-kB signaling in striatal cell Huntington's disease models

Proper development of neuronal cells is important for brain functions, and impairment of neuronal development may lead to neuronal disorders, implying that improvement in neuronal development may be a therapeutic direction for these diseases. Huntingtons disease (HD) is a neurodegenerative disease characterized by impairment of neuronal structures, ultimately leading to neuronal death and dysfunctions of the central nervous system. Based on previous studies, fibroblast growth factor 9 (FGF9) may provide neuroprotective functions in HD, and FGFs may enhance neuronal development and neurite outgrowth. However, whether FGF9 can provide neuronal protective functions through improvement of neuronal morphology in HD is still unclear. Here, we study the effects of FGF9 on neuronal morphology in HD and attempt to understand the related working mechanisms. Taking advantage of striatal cell lines from HD knock-in mice, we found that FGF9 increases neurite outgrowth and upregulates several structural and synaptic proteins under HD conditions. In addition, activation of nuclear factor kappa B (NF-kB) signaling by FGF9 was observed to be significant in HD cells, and blockage of NF-kB leads to suppression of these structural and synaptic proteins induced by FGF9, suggesting the involvement of NF-kB signaling in these effects of FGF9. Taken these results together, FGF9 may enhance neurite outgrowth through upregulation of NF-kB signaling, and this mechanism could serve as an important mechanism for neuroprotective functions of FGF9 in HD.

neuroscience↗

Reciprocal transplant experiment in lakes with disparate trophic states show resolution dependent partial functional redundancy

Microbial communities are considered to be functionally redundant, but few studies have tested this hypothesis empirically. In this study, we performed an in situ reciprocal transplant experiment on the surface and bottom waters of two lakes with disparate trophic states and tracked changes in their microbial community and functional attributes for 6 weeks using high-throughput sequencing and functional approaches. The communities from both lakes were resistant to changes in composition after the reciprocal transplant, but their functions tended to become similar to the incubating lakes functional profiles. A significant linear positive relationship was observed between the microbial community and functional attributes, though with varying scales of similarity, suggesting partial functional redundancy. Furthermore, the entropy-based L-divergence measure quantified the scale of partial functional redundancy in the lakes surface and bottom waters. This study establishes and quantifies the scale of partial functional redundancy in the freshwater ecosystem through empirical investigation.

ecology↗

A genomic view of coral-associated Prosthecochloris and a companion sulfate-reducing bacterium

Endolithic microbial symbionts in the coral skeleton may play a pivotal role in maintaining coral health. However, compared to aerobic microorganisms, research on the roles of endolithic anaerobic microorganisms and microbe-microbe interactions in the coral skeleton are still in their infancy. In our previous study, we showed that a group of coral-associated Prosthecochloris (CAP), a genus of anaerobic green sulfur bacteria, was dominant in the skeleton of the coral Isopora palifera. Though CAP is diverse, the 16S rRNA phylogeny presents it as a distinct clade separate from other free-living Prosthecochloris. In this study, we build on previous research and further characterize the genomic and metabolic traits of CAP by recovering two new near-complete CAP genomes--Candidatus Prosthecochloris isoporaea and Candidatus Prosthecochloris sp. N1--from coral Isopora palifera endolithic cultures. Genomic analysis revealed that these two CAP genomes have high genomic similarities compared with other Prosthecochloris and harbor several CAP-unique genes. Interestingly, different CAP species harbor various pigment synthesis and sulfur metabolism genes, indicating that individual CAPs can adapt to a diversity of coral microenvironments. A novel near-complete SRB genome--Candidatus Halodesulfovibrio lyudaonia--was also recovered from the same culture. The fact that CAP and various sulfate-reducing bacteria (SRB) co-exist in coral endolithic cultures and coral skeleton highlights the importance of SRB in the coral endolithic community. Based on functional genomic analysis of Ca. P. sp. N1 and Ca. H. lyudaonia, we also propose a syntrophic relationship between the SRB and CAP in the coral skeleton. ImportanceLittle is known about the ecological roles of endolithic microbes in the coral skeleton; one potential role is as a nutrient source for their coral hosts. Here, we identified a close ecological relationship between CAP and SRB. Recovering novel near-complete CAP and SRB genomes from endolithic cultures in this study enabled us to understand the genomic and metabolic features of anaerobic endolithic bacteria in coral skeletons. These results demonstrate that CAP members with similar functions in carbon, sulfur, and nitrogen metabolisms harbor different light-harvesting components, suggesting that CAP in the skeleton adapts to niches with different light intensities. Our study highlights the potential ecological roles of CAP and SRB in coral skeletons and paves the way for future investigations into how coral endolithic communities will respond to environmental changes.

microbiology↗

Dominant coral bacterium Endozoicomonas acroporae metabolizes DMSP

Dominant coral-associated Endozoicomonas bacteria species are hypothesized to play a role in the coral-sulfur cycle by metabolizing Dimethylsulfoniopropionate (DMSP) into Dimethylsulfide (DMS); however, no sequenced genome to date harbors genes for this process. In this study, we assembled high-quality (>95% complete) genomes of strains of a recently added species Endozoicomonas acroporae (Acr-14T, Acr-1 and Acr-5) isolated from the coral Acropora muricata and performed comparative genomic analysis on genus Endozoicomonas. We identified the first DMSP CoA-transferase/lyase--a dddD gene homolog found in all E. acroporae strains--and functionally characterized bacteria capable of metabolizing DMSP into DMS via the DddD cleavage pathway using RT-qPCR and gas chromatography (GC). Furthermore, we demonstrated that E. acroporae strains can use DMSP as the sole carbon source and have genes arranged in an operon-like manner to link DMSP metabolism to the central carbon cycle. This study confirms the role of Endozoicomonas in the coral sulfur cycle.

ecology↗

ZIC3 controls the transition from naïve to primed pluripotency.

Embryonic stem cells (ESCs) are pluripotent in nature, meaning that they have the capacity to differentiate into any cell in the body. However, to do so they must transition through a series of intermediate cell states before becoming terminally differentiated. A lot is known about how ESCs maintain their pluripotent state but comparatively less about how they exit this state and begin the transition towards differentiated cells. Here we investigated the earliest events in this transition by determining the changes in the open chromatin landscape as naive mouse ESCs transition to epiblast-like cells (EpiLCs). Motif enrichment analysis of the newly opening regions coupled with expression analysis identified ZIC3 as a potential regulator of this cell fate transition. Chromatin binding and genome-wide transcriptional profiling confirmed ZIC3 as an important regulatory transcription factor and among its targets are genes encoding a number of transcription factors. Among these is GRHL2 which acts through enhancer switching to maintain the expression of a subset of genes from the ESC state. Our data therefore place ZIC3 at the top of a cascade of transcriptional regulators and provide an important advance in our understanding of the regulatory factors governing the earliest steps in ESC differentiation.\n\nHighlightsO_LIThe transcription factor ZIC3 drives gene expression changes in the ESC to EpiLC transition.\nC_LIO_LIExtensive changes occur in the open chromatin landscape as ESCs progress to EpiLCs.\nC_LIO_LIZIC3 activates the expression of a network of transcription factors.\nC_LIO_LIZIC3 activated genes in EpiLCs are upregulated in the post-implantation epiblast.\nC_LI

developmental biology↗