A single-cell chromatin accessibility dataset of human primed and naïve pluripotent stem cell-derived teratoma.

Teratoma, due to its remarkable ability to differentiate into multiple cell lineages, is a valuable model for studying human embryonic development. The similarity of the gene expression and chromatin accessibility patterns in these cells to those observed in vivo further underscores its potential as a research tool. Notably, teratomas derived from human naïve (pre-implantation epiblast-like) pluripotent stem cells (PSCs) have larger embryonic cell diversity and contain extraembryonic lineages, making them more suitable to study developmental processes. However, the cell type-specific epigenetic profiles of naïve PSC teratomas have not been yet characterized. Using single-cell assay for transposase-accessible chromatin sequencing (scATAC-seq), we analyzed 66,384 cell profiles from five teratomas derived from human naïve PSCs and their post-implantation epiblast-like (primed) counterparts. We observed 17 distinct cell types from both embryonic and extraembryonic lineages, resembling the corresponding cell types in human fetal tissues. Additionally, we identified key transcription factors specific to different cell types. Our dataset provides a resource for investigating gene regulatory programs in a relevant model of human embryonic development.

γ-MnO2 as an Electron Reservoir for RuO2 Oxygen Evolution Catalyst in Acidic Media.

Developing highly active and durable catalysts in acid conditions remains an urgent issue due to the sluggish kinetics of oxygen evolution reaction (OER). Although RuO2 has been a state-of-the-art commercial catalyst for OER, it encounters poor stability and high cost. In this study, the electronic reservoir regulation strategy is proposed to promote the performance of acidic water oxidation via constructing a RuO2/MnO2 heterostructure supported on carbon cloth (CC) (abbreviated as RuO2/MnO2/CC). Theoretical and experimental results reveal that MnO2 acts as an electron reservoir for RuO2. It facilitates electron transfer from RuO2, enhancing its activity prior to OER, and donates electrons to RuO2, improving its stability after OER. Consequently, RuO2/MnO2/CC exhibits better performance compared to commercial RuO2, with an ultrasmall overpotential of 189 mV at 10 mA cm-2 and no signs of deactivation even after 800 h of electrolysis in 0.5 m H2SO4 at 10 mA cm-2. When applied as the anode in a proton exchange membrane water electrolyzer, the cost-efficient RuO2/MnO2/CC catalyst only requires a cell voltage of 1.661 V to achieve the water-splitting current of 1 A cm-2, and the noble metal cost is as low as US$ 0.00962 cm-2, indicating potential for practical applications.

Computational chemistry for water-splitting electrocatalysis.

Electrocatalytic water splitting driven by renewable electricity has attracted great interest in recent years for producing hydrogen with high-purity. However, the practical applications of this technology are limited by the development of electrocatalysts with high activity, low cost, and long durability. In the search for new electrocatalysts, computational chemistry has made outstanding contributions by providing fundamental laws that govern the electron behavior and enabling predictions of electrocatalyst performance. This review delves into theoretical studies on electrochemical water-splitting processes. Firstly, we introduce the fundamentals of electrochemical water electrolysis and subsequently discuss the current advancements in computational methods and models for electrocatalytic water splitting. Additionally, a comprehensive overview of benchmark descriptors is provided to aid in understanding intrinsic catalytic performance for water-splitting electrocatalysts. Finally, we critically evaluate the remaining challenges within this field.

VGLL1 cooperates with TEAD4 to control human trophectoderm lineage specification.

In contrast to rodents, the mechanisms underlying human trophectoderm and early placenta specification are understudied due to ethical barriers and the scarcity of embryos. Recent reports have shown that human pluripotent stem cells (PSCs) can differentiate into trophectoderm (TE)-like cells (TELCs) and trophoblast stem cells (TSCs), offering a valuable in vitro model to study early placenta specification. Here, we demonstrate that the VGLL1 (vestigial-like family member 1), which is highly expressed during human and non-human primate TE specification in vivo but is negligibly expressed in mouse, is a critical regulator of cell fate determination and self-renewal in human TELCs and TSCs derived from naïve PSCs. Mechanistically, VGLL1 partners with the transcription factor TEAD4 (TEA domain transcription factor 4) to regulate chromatin accessibility at target gene loci through histone acetylation and acts in cooperation with GATA3 and TFAP2C. Our work is relevant to understand primate early embryogenesis and how it differs from other mammalian species.

Live birth of chimeric monkey with high contribution from embryonic stem cells.

A formal demonstration that mammalian pluripotent stem cells possess preimplantation embryonic cell-like (naive) pluripotency is the generation of chimeric animals through early embryo complementation with homologous cells. Whereas such naive pluripotency has been well demonstrated in rodents, poor chimerism has been achieved in other species including non-human primates due to the inability of the donor cells to match the developmental state of the host embryos. Here, we have systematically tested various culture conditions for establishing monkey naive embryonic stem cells and optimized the procedures for chimeric embryo culture. This approach generated an aborted fetus and a live chimeric monkey with high donor cell contribution. A stringent characterization pipeline demonstrated that donor cells efficiently (up to 90%) incorporated into various tissues (including the gonads and placenta) of the chimeric monkeys. Our results have major implications for the study of primate naive pluripotency and genetic engineering of non-human primates.

Genome-wide identification, characterization, evolution and expression analysis of the DIR gene family in potato (Solanum tuberosum).

The dirigent (DIR) gene is a key player in environmental stress response and has been identified in many multidimensional tube plant species. However, there are few studies on the StDIR gene in potato. In this study, we used genome-wide identification to identify 31 StDIR genes in potato. Among the 12 potato chromosomes, the StDIR gene was distributed on 11 chromosomes, among which the third chromosome did not have a family member, while the tenth chromosome had the most members with 11 members. 22 of the 31 StDIRs had a classical DIR gene structure, with one exon and no intron. The conserved DIR domain accounts for most of the proteins in the 27 StDIRs. The structure of the StDIR gene was analyzed and ten different motifs were detected. The StDIR gene was divided into three groups according to its phylogenetic relationship, and 22 duplicate genes were identified. In addition, four kinds of cis-acting elements were detected in all 31 StDIR promoter regions, most of which were associated with biotic and abiotic stress. The findings demonstrated that the StDIR gene exhibited specific responses to cold stress, salt stress, ABA, and drought stress. This study provides new candidate genes for improving potato's resistance to stress.

Generation of a humanized mesonephros in pigs from induced pluripotent stem cells via embryo complementation.

Heterologous organ transplantation is an effective way of replacing organ function but is limited by severe organ shortage. Although generating human organs in other large mammals through embryo complementation would be a groundbreaking solution, it faces many challenges, especially the poor integration of human cells into the recipient tissues. To produce human cells with superior intra-niche competitiveness, we combined optimized pluripotent stem cell culture conditions with the inducible overexpression of two pro-survival genes (MYCN and BCL2). The resulting cells had substantially enhanced viability in the xeno-environment of interspecies chimeric blastocyst and successfully formed organized human-pig chimeric middle-stage kidney (mesonephros) structures up to embryonic day 28 inside nephric-defective pig embryos lacking SIX1 and SALL1. Our findings demonstrate proof of principle of the possibility of generating a humanized primordial organ in organogenesis-disabled pigs, opening an exciting avenue for regenerative medicine and an artificial window for studying human kidney development.

Cynomolgus monkey embryo model captures gastrulation and early pregnancy.

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 vitro culture (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 vitro gastrulation and in vivo early 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.

Holistic-Guided Disentangled Learning With Cross-Video Semantics Mining for Concurrent First-Person and Third-Person Activity Recognition.

The popularity of wearable devices has increased the demands for the research on first-person activity recognition. However, most of the current first-person activity datasets are built based on the assumption that only the human-object interaction (HOI) activities, performed by the camera-wearer, are captured in the field of view. Since humans live in complicated scenarios, in addition to the first-person activities, it is likely that third-person activities performed by other people also appear. Analyzing and recognizing these two types of activities simultaneously occurring in a scene is important for the camera-wearer to understand the surrounding environments. To facilitate the research on concurrent first-and third-person activity recognition (CFT-AR), we first created a new activity dataset, namely PolyU concurrent first-and third-person (CFT) Daily, which exhibits distinct properties and challenges, compared with previous activity datasets. Since temporal asynchronism and appearance gap usually exist between the first-and third-person activities, it is crucial to learn robust representations from all the activity-related spatio-temporal positions. Thus, we explore both holistic scene-level and local instance-level (person-level) features to provide comprehensive and discriminative patterns for recognizing both first-and third-person activities. On the one hand, the holistic scene-level features are extracted by a 3-D convolutional neural network, which is trained to mine shared and sample-unique semantics between video pairs, via two well-designed attention-based modules and a self-knowledge distillation (SKD) strategy. On the other hand, we further leverage the extracted holistic features to guide the learning of instance-level features in a disentangled fashion, which aims to discover both spatially conspicuous patterns and temporally varied, yet critical, cues. Experimental results on the PolyU CFT Daily dataset validate that our method achieves the state-of-the-art performance.

Rolling back human pluripotent stem cells to an eight-cell embryo-like stage.

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 blastoids5 and complex teratomas. Our approach provides a resource to uncover the molecular process of early human embryogenesis.

Ni/AntPohs-Catalyzed Stereoselective Asymmetric Intramolecular Reductive Coupling of N-1,6-Alkynones.

An efficient nickel-catalyzed stereoselective asymmetric intramolecular reductive coupling of N-1,6-alkynones is reported. A P-chiral monophosphine ligand AntPhos was found to be a privileged catalyst for constructing versatile functionalized chiral pyrrolidine rings using triethylsilane as the reducing reagent. Concise synthesis of pyrrolidines with chiral tertiary allylic alcohols was achieved in high yields (99%), excellent stereoselectivity (>99:1 E/Z), and enantioselectivity (>99:1 er) with very broad substrate scope. Totally, thirty-five N-1,6-alkynones were synthesized and applied in this reaction successfully. This reaction can be scaled up to gram scale without loss of its enantioselectivity. Ligand effects and reaction mechanism are investigated in detail. While the developed asymmetric synthesis of pyrrolidine with chiral tertiary allylic alcohols is anticipated to find wider applications in organic synthesis and chemical biology, the discovered new reactions of N-1,6-alkynone with AntPhos using different catalyst systems would further expanded its new research fields and attract more detailed explorations in the future.