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Estimating potential casualties from a significant earthquake and tsunami event is crucial to enhance disaster preparedness and response. Although various approaches exist to assess potential casualties, few studies have made direct comparisons between them. The present study aimed to clarify the differences in the estimation of casualties between an agent-based model (ABM), which can capture detailed evacuation behavior but demands significant computational resources, and a simplified approach at less computational cost by assuming that evacuees would move along a straight line from their initial location to the closest evacuation destination. These different approaches were applied to three coastal cities in Japan—Mihama, Kushimoto, and Shingu in Wakayama Prefecture—revealing significant differences in the estimated results between the ABM and the simplified approach. Notably, when the effects of building collapse due to an earthquake were considered, the mortality rates estimated by the ABM were higher than those estimated by the simplified approach in the three cities. There were also significant differences in the spatial distribution of the estimated mortality rates between the ABM and the simplified approach. The findings suggest that while the simplified approach can yield results more quickly, casualty estimates derived from such models should be interpreted with caution.

The mechanism by which mammalian liver cell responses are coordinated during tissue homeostasis and perturbation is poorly understood, representing a major obstacle in our understanding of many diseases. This knowledge gap is caused by the difficulty involved with studying multiple cell types in different states and locations, particularly when these are transient. We have combined Stereo-seq (spatiotemporal enhanced resolution omics-sequencing) with single-cell transcriptomic profiling of 473,290 cells to generate a high-definition spatiotemporal atlas of mouse liver homeostasis and regeneration at the whole-lobe scale. Our integrative study dissects in detail the molecular gradients controlling liver cell function, systematically defining how gene networks are dynamically modulated through intercellular communication to promote regeneration. Among other important regulators, we identified the transcriptional cofactor TBL1XR1 as a rheostat linking inflammation to Wnt/β-catenin signaling for facilitating hepatocyte proliferation. Our data and analytical pipelines lay the foundation for future high-definition tissue-scale atlases of organ physiology and malfunction.

Cholestatic liver injuries, characterized by regional damage around the bile ductular region, lack curative therapies and cause considerable mortality. Here we generated a high-definition spatiotemporal atlas of gene expression during cholestatic injury and repair in mice by integrating spatial enhanced resolution omics sequencing and single-cell transcriptomics. Spatiotemporal analyses revealed a key role of cholangiocyte-driven signaling correlating with the periportal damage-repair response. Cholangiocytes express genes related to recruitment and differentiation of lipid-associated macrophages, which generate feedback signals enhancing ductular reaction. Moreover, cholangiocytes express high TGFβ in association with the conversion of liver progenitor-like cells into cholangiocytes during injury and the dampened proliferation of periportal hepatocytes during recovery. Notably, Atoh8 restricts hepatocyte proliferation during 3,5-diethoxycarbonyl-1,4-dihydro-collidin damage and is quickly downregulated after injury withdrawal, allowing hepatocytes to respond to growth signals. Our findings lay a keystone for in-depth studies of cellular dynamics and molecular mechanisms of cholestatic injuries, which may further develop into therapies for cholangiopathies.

Muscle atrophy and functional decline (sarcopenia) are common manifestations of frailty and are critical contributors to morbidity and mortality in older people1. Deciphering the molecular mechanisms underlying sarcopenia has major implications for understanding human ageing2. Yet, progress has been slow, partly due to the difficulties of characterizing skeletal muscle niche heterogeneity (whereby myofibres are the most abundant) and obtaining well-characterized human samples3,4. Here we generate a single-cell/single-nucleus transcriptomic and chromatin accessibility map of human limb skeletal muscles encompassing over 387,000 cells/nuclei from individuals aged 15 to 99 years with distinct fitness and frailty levels. We describe how cell populations change during ageing, including the emergence of new populations in older people, and the cell-specific and multicellular network features (at the transcriptomic and epigenetic levels) associated with these changes. On the basis of cross-comparison with genetic data, we also identify key elements of chromatin architecture that mark susceptibility to sarcopenia. Our study provides a basis for identifying targets in the skeletal muscle that are amenable to medical, pharmacological and lifestyle interventions in late life.

The N6-methyladenosine (m6A) RNA modification plays essential roles in multiple biological processes, including stem cell fate determination. To explore the role of the m6A modification in pluripotent reprogramming, we used RNA-seq to map m6A effectors in human iPSCs, fibroblasts, and H9 ESCs, as well as in mouse ESCs and fibroblasts. By integrating the human and mouse RNA-seq data, we found that 19 m6A effectors were significantly upregulated in reprogramming. Notably, IGF2BPs, particularly IGF2BP1, were among the most upregulated genes in pluripotent cells, while YTHDF3had high levels of expression in fibroblasts. Using quantitative PCR and Western blot, we validated the pluripotency-associated elevation of IGF2BPs. Knockdown of IGF2BP1induced the downregulation of stemness genes and exit from pluripotency. Proteome analysis of cells collected at both the beginning and terminal states of the reprogramming process revealed that the IGF2BP1 protein was positively correlated with stemness markers SOX2 and OCT4. The eCLIP-seq target analysis showed that IGF2BP1 interacted with the coding sequence (CDS) and 3’UTR regions of the SOX2transcripts, in agreement with the location of m6A modifications. This study identifies IGF2BP1as a vital pluripotency-associated m6A effector, providing new insight into the interplay between m6A epigenetic modifications and pluripotent reprogramming.

After fertilization, the quiescent zygote experiences a burst of genome activation that initiates a short-lived totipotent state. Understanding the process of totipotency in human cells would have broad applications. However, in contrast to in mice1,2, demonstration of the time of zygotic genome activation or the eight-cell (8C) stage in in vitro cultured human cells has not yet been reported, and the study of embryos is limited by ethical and practical considerations. Here we describe a transgene-free, rapid and controllable method for producing 8C-like cells (8CLCs) from human pluripotent stem cells. Single-cell analysis identified key molecular events and gene networks associated with this conversion. Loss-of-function experiments identified fundamental roles for DPPA3, a master regulator of DNA methylation in oocytes3, and TPRX1, a eutherian totipotent cell homeobox (ETCHbox) family transcription factor that is absent in mice4. DPPA3 induces DNA demethylation throughout the 8CLC conversion process, whereas TPRX1 is a key executor of 8CLC gene networks. We further demonstrate that 8CLCs can produce embryonic and extraembryonic lineages in vitro or in vivo in the form of blastoids5and complex teratomas. Our approach provides a resource to uncover the molecular process of early human embryogenesis.

Studying tissue composition and function in non-human primates (NHPs) is crucial to understand the nature of our own species. Here we present a large-scale cell transcriptomic atlas that encompasses over 1 million cells from 45 tissues of the adult NHP Macaca fascicularis. This dataset provides a vast annotated resource to study a species phylogenetically close to humans. To demonstrate the utility of the atlas, we have reconstructed the cell–cell interaction networks that drive Wnt signalling across the body, mapped the distribution of receptors and co-receptors for viruses causing human infectious diseases, and intersected our data with human genetic disease orthologues to establish potential clinical associations. Our M. fasciculariscell atlas constitutes an essential reference for future studies in humans and NHPs.

Tissue regeneration requires coordination between resident stem cells and local niche cells1,2. Here we identify that senescent cells are integral components of the skeletal muscle regenerative niche that repress regeneration at all stages of life. The technical limitation of senescent-cell scarcity3was overcome by combining single-cell transcriptomics and a senescent-cell enrichment sorting protocol. We identified and isolated different senescent cell types from damaged muscles of young and old mice. Deeper transcriptome, chromatin and pathway analyses revealed conservation of cell identity traits as well as two universal senescence hallmarks (inflammation and fibrosis) across cell type, regeneration time and ageing. Senescent cells create an aged-like inflamed niche that mirrors inflammation associated with ageing (inflammageing4) and arrests stem cell proliferation and regeneration. Reducing the burden of senescent cells, or reducing their inflammatory secretome through CD36 neutralization, accelerates regeneration in young and old mice. By contrast, transplantation of senescent cells delays regeneration. Our results provide a technique for isolating in vivo senescent cells, define a senescence blueprint for muscle, and uncover unproductive functional interactions between senescent cells and stem cells in regenerative niches that can be overcome. As senescent cells also accumulate in human muscles, our findings open potential paths for improving muscle repair throughout life.

Application of synthetic nucleoside analogues to capture newly transcribed RNAs has unveiled key features of RNA metabolism. Whether this approach could be adapted to isolate the RNA-bound proteome (RNA interactome) was, however, unexplored. We have developed a new method (capture of the newly transcribed RNA interactome using click chemistry, or RICK) for the systematic identification of RNA-binding proteins based on the incorporation of 5-ethynyluridine into newly transcribed RNAs followed by UV cross-linking and click chemistry-mediated biotinylation. The RNA–protein adducts are then isolated by affinity capture using streptavidin-coated beads. Through high-throughput RNA sequencing and mass spectrometry, the RNAs and proteins can be elucidated globally. A typical RICK experimental procedure takes only 1 d, excluding the steps of cell preparation, 5-ethynyluridine labeling, validation (silver staining, western blotting, quantitative reverse-transcription PCR (qRT-PCR) or RNA sequencing (RNA-seq)) and proteomics. Major advantages of RICK are the capture of RNA-binding proteins interacting with any type of RNA and, particularly, the ability to discern between newly transcribed and steady-state RNAs through controlled labeling. Thanks to its versatility, RICK will facilitate the characterization of the total and newly transcribed RNA interactome in different cell types and conditions.

Purpose: This study adopts the multi-step model developed by Avraham and Ketter (2008), for altering place images, based on past academic literature on destination marketing. The purpose of this study is to determine the state of Fukushima’s sake breweries before and after 2011, and its strategies for overcoming negative images and strengthening regional branding. Semi-structured interviews were conducted with seven sake breweries in Fukushima. Design/methodology/approach: Fukushima Prefecture, located in northern Japan, is renowned for its hot springs, lakes, historical architecture, gastronomy, and particularly its sake (or Japanese rice wine). However, pre-existing problems such as the prefecture’s changing demographics and economic development, the effects of the 2011 Great East Japan Earthquake (GEJE) and fears of radioactive contamination have made consumers reluctant to consume products from the region or to visit the prefecture. This study illustrates how various sake brewery stakeholders have sought to reverse and alter negative images associated with the prefecture. To examine these initiatives, this study uses the multi-step destination marketing and counter-branding model to identify the strategies and techniques used by the stakeholders, with the aim of altering the way the prefecture is perceived and reversing the negative image people may have of the prefecture. To acquire data for this model, this study uses semi-structured interviews conducted in 2018 and 2020 with local sake breweries, tourism associations and the local government on how they sought to retore a positive image of the prefecture and rebrand it into a new type of tourism destination that focuses on the strengths of its breweries. Findings: The results indicate that through a combination of collaboration between the breweries, local government and the local communities, the sake breweries were able to reverse many of the negative effects of the 2011 GEJE. The success of the sake industry has prompted the local government to focus more strongly on tourism marketing that places sake products and breweries at the center of its campaign to promote the region. Research limitations/implications: While this paper focuses on the recovery of breweries, it does not include the recovery of wineries in Fukushima, which have made similar progress in their recovery. In addition, the interviews focused primarily on the perspectives of the suppliers and not the consumers. Practical implications: The results of this research can help guide other destinations undergoing prolonged association with negative images on the path toward image recovery. In particular, this paper highlights the importance of a coordinated strategy by all stakeholders, the local government, businesses and communities, to create a united image and response for addressing the causes of these image problems and to create new opportunities for all stakeholders. Originality/value: This research contributes to the field of image restoration, which combines theories regarding destination marketing and crisis management. Also, the research highlights the importance of collective stakeholder mobilization when attempting to help communities that are facing economic and tourism crises.

This review discusses climate hazards and specific risks associated with existing and new nuclear power plants under global warming level futures, with an emphasis on water-based risks for plants that rely on traditional water-cooling processes. Projected hazards, including extreme heatwaves, sea-level rise, and altered precipitation patterns pose significant challenges to the safe and efficient operation of nuclear plants. Additional risks include reduced water-cooling system efficiency, clogging due to biological contamination of water streams, water access issues in reactors during droughts, disruptions from extreme storms, and coastal sea level rise. These findings emphasise the importance of formulating appropriate adaptation strategies that incorporate enhanced safety measures in the planning and design of new nuclear facilities. Incorporating these specific risks into mitigation scenarios and decision-making processes for nuclear energy expansion or modernisation is crucial to improve the resilience of such infrastructure in the face of a changing climate.

Pluripotent stem cells (PSCs) can be expanded in vitroin different culture conditions, resulting in a spectrum of cell states with distinct properties. Understanding how PSCs transition from one state to another, ultimately leading to lineage-specific differentiation, is important for developmental biology and regenerative medicine. Although there is significant information regarding gene expression changes controlling these transitions, less is known about post-translational modifications of proteins. Protein crotonylationis a newly discovered post-translational modification where lysine residues are modified with a crotonyl group. Here, we employed affinity purification of crotonylated peptides and liquid chromatography–tandem mass spectrometry (LC–MS/MS) to systematically profile protein crotonylation in mouse PSCs in different states including ground, metastable, and primed states, as well as metastable PSCs undergoing early pluripotencyexit. We successfully identified 3628 high-confidence crotonylated sites in 1426 proteins. These crotonylated proteins are enriched for factors involved in functions/processes related to pluripotency such as RNA biogenesis, central carbon metabolism, and proteasomefunction. Moreover, we found that increasing the cellular levels of crotonyl-coenzyme A (crotonyl-CoA) through crotonic acid treatment promotes proteasome activity in metastable PSCs and delays their differentiation, consistent with previous observations showing that enhanced proteasome activity helps to sustain pluripotency. Our atlas of protein crotonylation will be valuable for further studies of pluripotency regulation and may also provide insights into the role of metabolism in other cell fate transitions.

Amyotrophic lateral sclerosis (ALS) was initially thought to be associated with oxidative stress when it was first linked to mutant superoxide dismutase 1 (SOD1). The subsequent discovery of ALS-linked genes functioning in RNA processing and proteostasis raised the question of how different biological pathways converge to cause the disease. Both familial and sporadic ALS are characterized by the aggregation of the essential DNA- and RNA-binding protein TDP-43, suggesting a central role in ALS etiology. Here we report that TDP-43 aggregation in neuronal cells of mouse and human origin causes sensitivity to oxidative stress. Aggregated TDP-43 sequesters specific microRNAs (miRNAs) and proteins, leading to increased levels of some proteins while functionally depleting others. Many of those functionally perturbed gene products are nuclear-genome-encoded mitochondrial proteins, and their dysregulation causes a global mitochondrial imbalance that augments oxidative stress. We propose that this stress-aggregation cycle may underlie ALS onset and progression.

Pluripotent stem cells (PSCs) can be expanded in vitroin different culture conditions, resulting in a spectrum of cell states with distinct properties. Understanding how PSCs transition from one state to another, ultimately leading to lineage-specific differentiation, is important for developmental biology and regenerative medicine. Although there is significant information regarding gene expression changes controlling these transitions, less is known about post-translational modifications of proteins. Protein crotonylationis a newly discovered post-translational modification where lysine residues are modified with a crotonyl group. Here, we employed affinity purification of crotonylated peptides and liquid chromatography–tandem mass spectrometry (LC–MS/MS) to systematically profile protein crotonylation in mouse PSCs in different states including ground, metastable, and primed states, as well as metastable PSCs undergoing early pluripotencyexit. We successfully identified 3628 high-confidence crotonylated sites in 1426 proteins. These crotonylated proteins are enriched for factors involved in functions/processes related to pluripotency such as RNA biogenesis, central carbon metabolism, and proteasomefunction. Moreover, we found that increasing the cellular levels of crotonyl-coenzyme A (crotonyl-CoA) through crotonic acid treatment promotes proteasome activity in metastable PSCs and delays their differentiation, consistent with previous observations showing that enhanced proteasome activity helps to sustain pluripotency. Our atlas of protein crotonylation will be valuable for further studies of pluripotency regulation and may also provide insights into the role of metabolism in other cell fate transitions.

This paper introduces a research methodology to collect sensitive data when facing the creation of design for sustainability (DfS) approaches in the context of natural disasters. Through the gamification of interviews, the authors attempt to overcome interview fatigue (IF) symptoms presented by survivors of natural disasters. As a result, the research was able to establish the different necessities and barriers the elderly faced in the aftermath of the 2011 tsunami in Japan. The results indicated: a) the game created an environment where elderly survivors felt comfortable to share their experiences and thoughts; and b) it allowed them to think and discuss together their needs and strengths in order to propose solutions to improve future disaster resilience.

Southeast Asia’s coastal urban areas continue to grow, with land reclamation fast becoming an important option for megacities to address issues of economic growth and increasing population density. Experts are divided over the advantages and disadvantages of land reclamation, though this process continues unabated, exposing settlements to coastal hazards. The Bataan Shipping and Engineering Company (BASECO) compound is an informal settlement on reclaimed land in Manila, the Philippines. How informal coastal settlements view disaster risk and their more pressing socioeconomic needs is crucial to understanding the potentials and repercussions of land reclamation. Using a topographic survey, a questionnaire survey, and the protective action decision model, this study explored the perception of disasters and land reclamation of informal settlers who are living on reclaimed land. The study found that people are aware of disaster risks, but are more concerned with everyday needs. They are divided on the issue of further land reclamation. Residents on the original non-reclaimed land view it as a coastal defense, while those on reclaimed land fear potential eviction. Despite this, all locations in the community are concerned with the loss of jobs, economic opportunities, and eviction, rather than potential disasters.

The generation of induced pluripotent stem cells through somatic cell reprogramming requires a global reorganization of cellular functions. This reorganization occurs in a multi-phased manner and involves a gradual revision of both the epigenome and transcriptome. Recent studies have shown that the large-scale transcriptional changes observed during reprogramming also apply to long non-coding RNAs (lncRNAs), a type of traditionally neglected RNA species that are increasingly viewed as critical regulators of cellular function. Deeper understanding of lncRNAs in reprogramming may not only help to improve this process but also have implications for studying cell plasticity in other contexts, such as development, aging, and cancer. In this review, we summarize the current progress made in profiling and analyzing the role of lncRNAs in various phases of somatic cell reprogramming, with emphasis on the re-establishment of the pluripotency gene network and X chromosome reactivation.

The generation of induced pluripotent stem cells through somatic cell reprogramming requires a global reorganization of cellular functions. This reorganization occurs in a multi-phased manner and involves a gradual revision of both the epigenome and transcriptome. Recent studies have shown that the large-scale transcriptional changes observed during reprogramming also apply to long non-coding RNAs (lncRNAs), a type of traditionally neglected RNA species that are increasingly viewed as critical regulators of cellular function. Deeper understanding of lncRNAs in reprogramming may not only help to improve this process but also have implications for studying cell plasticity in other contexts, such as development, aging, and cancer. In this review, we summarize the current progress made in profiling and analyzing the role of lncRNAs in various phases of somatic cell reprogramming, with emphasis on the re-establishment of the pluripotency gene network and X chromosome reactivation.

La incidencia de infección de dispositivos electrónicos implantables cardíacos supone 1,9 por 1.000 dispositivos-año.

Long noncoding RNAs (lncRNAs) can regulate the activity of target genes by participating in the organization of chromatin architecture. We have devised a “chromatin-RNA in situ reverse transcription sequencing” (CRIST-seq) approach to profile the lncRNA interaction network in gene regulatory elements by combining the simplicity of RNA biotin labeling with the specificity of the CRISPR/Cas9 system. Using gene-specific gRNAs, we describe a pluripotency-specific lncRNA interacting network in the promoters of Sox2and Pou5f1, two critical stem cell factors that are required for the maintenance of pluripotency. The promoter-interacting lncRNAs were specifically activated during reprogramming into pluripotency. Knockdown of these lncRNAs caused the stem cells to exit from pluripotency. In contrast, overexpression of the pluripotency-associated lncRNA activated the promoters of core stem cell factor genes and enhanced fibroblast reprogramming into pluripotency. These CRIST-seq data suggest that the Sox2and Pou5f1promoters are organized within a unique lncRNA interaction network that determines the fate of pluripotency during reprogramming. This CRIST approach may be broadly used to map lncRNA interaction networks at target loci across the genome.

This article presents the case for IT transformation and big data for safety risk management on the GB railways. This article explains why the interest in data-driven safety solutions is very high in the railways by describing the drivers that shape risk management for the railways. A brief overview of research projects in the big data risk analysis programme supports the case and helps understand the research agenda for the transformation of safety and risk on the GB railways. The drivers and the projects provide insight in the current research needs for the transformation and explains why safety researchers have to broaden their skill set to include digital skills and potentially even programming. The case for IT transformation of risk management systems is compelling, and this article describes just the tip of the iceberg of opportunities opening up for safety analysis that, after all, depends on data.

Somatic cell reprogramming by exogenous factors requires cooperation with transcriptional co-activators and co-repressors to effectively remodel the epigenetic environment. How this interplay is regulated remains poorly understood. Here, we demonstrate that NCoR/SMRT co-repressors bind to pluripotency loci to create a barrier to reprogramming with the four Yamanaka factors (OCT4, SOX2, KLF4 and c-MYC), and consequently, suppressing NCoR/SMRT significantly enhances reprogramming efficiency and kinetics. The core epigenetic subunit of the NCoR/SMRT complex, histone deacetylase 3 (HDAC3), contributes to the effects of NCoR/SMRT by inducing histone deacetylation at pluripotency loci. Among the Yamanaka factors, recruitment of NCoR/SMRT–HDAC3 to genomic loci is mostly facilitated by c-MYC. Hence, we describe how c-MYC is beneficial for the early phase of reprogramming but deleterious later. Overall, we uncover a role for NCoR/SMRT co-repressors in reprogramming and propose a dual function for c-MYC in this process. Zhuang et al. demonstrate that suppression of NCoR/SMRT enhances OSKM reprogramming efficiency, and that the barrier mechanism depends on the recruitment of HDAC3 to pluripotency loci by c-MYC.

Labeling newly transcribed RNA with 5-ethynyluridine and adding biotin via click chemistry allows the analysis of the proteome bound to the various RNA species, including nascent RNA.

Considerable evidence suggests that residential demand response enables demand-side flexibility, lowering average electric procurement costs and minimizing greenhouse gas emissions associated with the operation of peak power plants. However, the effectiveness of such demand management is contingent on behavioral interventions that attenuate energy saving at the residential level, highlighting the need to better understand the human dimension of residential electricity curtailment. This study examines the influence of interpersonal, socio-economic characteristics and environmental awareness of households in Ottawa on their willingness to participate in demand response programs. Time of use, real-time pricing, critical peak pricing, and direct load control were considered potential candidates for adoption. Furthermore, the authors propose and investigate the willingness of people to receive non-electricity-related information on their in-home displays and participate in an altruistic peer-to-peer energy platform that was conceptualized and designed by the authors. The results suggest that the corporate social and environmental responsibility of electricity providers and the environmental awareness of respondents, as well as their perceived level of indoor comfort, all influence the effectiveness of demand response. The findings also indicate that philanthropic-oriented and information-driven incentives can potentially increase energy curtailment amongst households with a high prosocial responsibility.

In the big data era, large and complex data sets will exceed scientists’ capacity to make sense of them in the traditional way. New approaches in data analysis, supported by computer science, will be necessary to address the problems that emerge with the rise of big data. The analysis of the Close Call database, which is a text-based database for near-miss reporting on the GB railways, provides a test case. The traditional analysis of Close Calls is time consuming and prone to differences in interpretation. This paper investigates the use of visual analytics techniques, based on network text analysis, to conduct data analysis and extract safety knowledge from 500 randomly selected Close Call records relating to worker slips, trips and falls. The results demonstrate a straightforward, yet effective, way to identify hazardous conditions without having to read each report individually. This opens up new ways to perform data analysis in safety science.

Most adaptation studies suggest that sea-level rise will lead to relocation as flooding worsens. Here we identified and evaluated potential adaptation strategies for adapting to sea-level rise, based on the experiences of four low-lying island communities in central Philippines that have experienced flooding during normal high tides since a 2013 earthquake that induced land subsidence. Coastal surveys, interviews and household questionnaires showed that island residents generally prefer in situ adaptation strategies rather than relocation to the mainland. These results are unexpected, particularly because a relocation programme has been developed by authorities on the mainland. Direct measurements during a flooding event indicate stilted housing as the most effective type of adaptation strategy. Many households have also raised their floors using coral stones, although this might inadvertently increase their vulnerability to typhoons and storm surges in the long-term.

Human stem cell-derived blastoids display similar morphology and cell lineages to normal blastocysts. However, the ability to investigate their developmental potential is limited. Here, we construct cynomolgus monkey blastoids resembling blastocysts in morphology and transcriptomics using naive ESCs. These blastoids develop to embryonic disk with the structures of yolk sac, chorionic cavity, amnion cavity, primitive streak, and connecting stalk along the rostral-caudal axis through prolonged in vitroculture (IVC). Primordial germ cells, gastrulating cells, visceral endoderm/yolk sac endoderm, three germ layers, and hemato-endothelial progenitors in IVC cynomolgus monkey blastoids were observed by single-cell transcriptomics or immunostaining. Moreover, transferring cynomolgus monkey blastoids to surrogates achieves pregnancies, as indicated by progesterone levels and presence of early gestation sacs. Our results reveal the capacity of in vitrogastrulation and in vivoearly pregnancy of cynomolgus monkey blastoids, providing a useful system to dissect primate embryonic development without the same ethical concerns and access challenges in human embryo study.