bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecularly defined and spatially resolved cell atlas of the whole mouse brain
Authors: Zhang Meng , Pan Xingjie , Jung Won , Halpern Aaron R. , Eichhorn Stephen W. , Lei Zhiyun , Cohen Limor , Smith Kimberly A. , Tasic Bosiljka , Yao Zizhen , Zeng Hongkui , Zhuang Xiaowei 
Published: December 2023

AbstractIn mammalian brains, millions to billions of cells form complex interaction networks to enable a wide range of functions. The enormous diversity and intricate organization of cells have impeded our understanding of the molecular and cellular basis of brain function. Recent advances in spatially resolved single-cell transcriptomics have enabled systematic mapping of the spatial organization of molecularly defined cell types in complex tissues1–3, including several brain regions (for example, refs. 1–11). However, a comprehensive cell atlas of the whole brain is still missing. Here we imaged a panel of more than 1,100 genes in approximately 10 million cells across the entire adult mouse brains using multiplexed error-robust fluorescence in situ hybridization12 and performed spatially resolved, single-cell expression profiling at the whole-transcriptome scale by integrating multiplexed error-robust fluorescence in situ hybridization and single-cell RNA sequencing data. Using this approach, we generated a comprehensive cell atlas of more than 5,000 transcriptionally distinct cell clusters, belonging to more than 300 major cell types, in the whole mouse brain with high molecular and spatial resolution. Registration of this atlas to the mouse brain common coordinate framework allowed systematic quantifications of the cell-type composition and organization in individual brain regions. We further identified spatial modules characterized by distinct cell-type compositions and spatial gradients featuring gradual changes of cells. Finally, this high-resolution spatial map of cells, each with a transcriptome-wide expression profile, allowed us to infer cell-type-specific interactions between hundreds of cell-type pairs and predict molecular (ligand–receptor) basis and functional implications of these cell–cell interactions. These results provide rich insights into the molecular and cellular architecture of the brain and a foundation for functional investigations of neural circuits and their dysfunction in health and disease.
The molecular cytoarchitecture of the adult mouse brain
Authors: Langlieb Jonah , Sachdev Nina S. , Balderrama Karol S. , Nadaf Naeem M. , Raj Mukund , Murray Evan , Webber James T. , Vanderburg Charles , Gazestani Vahid , Tward Daniel , Mezias Chris , Li Xu , Flowers Katelyn , Cable Dylan M. , Norton Tabitha , Mitra Partha , Chen Fei , Macosko Evan Z. 
Published: December 2023

AbstractThe function of the mammalian brain relies upon the specification and spatial positioning of diversely specialized cell types. Yet, the molecular identities of the cell types and their positions within individual anatomical structures remain incompletely known. To construct a comprehensive atlas of cell types in each brain structure, we paired high-throughput single-nucleus RNA sequencing with Slide-seq1,2—a recently developed spatial transcriptomics method with near-cellular resolution—across the entire mouse brain. Integration of these datasets revealed the cell type composition of each neuroanatomical structure. Cell type diversity was found to be remarkably high in the midbrain, hindbrain and hypothalamus, with most clusters requiring a combination of at least three discrete gene expression markers to uniquely define them. Using these data, we developed a framework for genetically accessing each cell type, comprehensively characterized neuropeptide and neurotransmitter signalling, elucidated region-specific specializations in activity-regulated gene expression and ascertained the heritability enrichment of neurological and psychiatric phenotypes. These data, available as an online resource (www.BrainCellData.org), should find diverse applications across neuroscience, including the construction of new genetic tools and the prioritization of specific cell types and circuits in the study of brain diseases.
Conserved and divergent gene regulatory programs of the mammalian neocortex
Authors: Zemke Nathan R. , Armand Ethan J. , Wang Wenliang , Lee Seoyeon , Zhou Jingtian , Li Yang Eric , Liu Hanqing , Tian Wei , Nery Joseph R. , Castanon Rosa G. , Bartlett Anna , Osteen Julia K. , Li Daofeng , Zhuo Xiaoyu , Xu Vincent , Chang Lei , Dong Keyi , Indralingam Hannah S. , Rink Jonathan A. , Xie Yang , Miller Michael , Krienen Fenna M. , Zhang Qiangge , Taskin Naz , Ting Jonathan , Feng Guoping , McCarroll Steven A. , Callaway Edward M. , Wang Ting , Lein Ed S. , Behrens M. Margarita , Ecker Joseph R. , Ren Bing 
Published: December 2023

AbstractDivergence of cis-regulatory elements drives species-specific traits1, but how this manifests in the evolution of the neocortex at the molecular and cellular level remains unclear. Here we investigated the gene regulatory programs in the primary motor cortex of human, macaque, marmoset and mouse using single-cell multiomics assays, generating gene expression, chromatin accessibility, DNA methylome and chromosomal conformation profiles from a total of over 200,000 cells. From these data, we show evidence that divergence of transcription factor expression corresponds to species-specific epigenome landscapes. We find that conserved and divergent gene regulatory features are reflected in the evolution of the three-dimensional genome. Transposable elements contribute to nearly 80% of the human-specific candidate cis-regulatory elements in cortical cells. Through machine learning, we develop sequence-based predictors of candidate cis-regulatory elements in different species and demonstrate that the genomic regulatory syntax is highly preserved from rodents to primates. Finally, we show that epigenetic conservation combined with sequence similarity helps to uncover functional cis-regulatory elements and enhances our ability to interpret genetic variants contributing to neurological disease and traits.
Slide-tags enables single-nucleus barcoding for multimodal spatial genomics
Authors: Russell Andrew J. C. , Weir Jackson A. , Nadaf Naeem M. , Shabet Matthew , Kumar Vipin , Kambhampati Sandeep , Raichur Ruth , Marrero Giovanni J. , Liu Sophia , Balderrama Karol S. , Vanderburg Charles R. , Shanmugam Vignesh , Tian Luyi , Iorgulescu J. Bryan , Yoon Charles H. , Wu Catherine J. , Macosko Evan Z. , Chen Fei 
Published: December 2023

AbstractRecent technological innovations have enabled the high-throughput quantification of gene expression and epigenetic regulation within individual cells, transforming our understanding of how complex tissues are constructed1–6. However, missing from these measurements is the ability to routinely and easily spatially localize these profiled cells. We developed a strategy, Slide-tags, in which single nuclei within an intact tissue section are tagged with spatial barcode oligonucleotides derived from DNA-barcoded beads with known positions. These tagged nuclei can then be used as an input into a wide variety of single-nucleus profiling assays. Application of Slide-tags to the mouse hippocampus positioned nuclei at less than 10 μm spatial resolution and delivered whole-transcriptome data that are indistinguishable in quality from ordinary single-nucleus RNA-sequencing data. To demonstrate that Slide-tags can be applied to a wide variety of human tissues, we performed the assay on brain, tonsil and melanoma. We revealed cell-type-specific spatially varying gene expression across cortical layers and spatially contextualized receptor–ligand interactions driving B cell maturation in lymphoid tissue. A major benefit of Slide-tags is that it is easily adaptable to almost any single-cell measurement technology. As a proof of principle, we performed multiomic measurements of open chromatin, RNA and T cell receptor (TCR) sequences in the same cells from metastatic melanoma, identifying transcription factor motifs driving cancer cell state transitions in spatially distinct microenvironments. Slide-tags offers a universal platform for importing the compendium of established single-cell measurements into the spatial genomics repertoire.
Bioactive glycans in a microbiome-directed food for children with malnutrition
Authors: Hibberd Matthew C. , Webber Daniel M. , Rodionov Dmitry A. , Henrissat Suzanne , Chen Robert Y. , Zhou Cyrus , Lynn Hannah M. , Wang Yi , Chang Hao-Wei , Lee Evan M. , Lelwala-Guruge Janaki , Kazanov Marat D. , Arzamasov Aleksandr A. , Leyn Semen A. , Lombard Vincent , Terrapon Nicolas , Henrissat Bernard , Castillo Juan J. , Couture Garret , Bacalzo Nikita P. , Chen Ye , Lebrilla Carlito B. , Mostafa Ishita , Das Subhasish , Mahfuz Mustafa , Barratt Michael J. , Osterman Andrei L. , Ahmed Tahmeed , Gordon Jeffrey I. 
Published: December 2023

AbstractEvidence is accumulating that perturbed postnatal development of the gut microbiome contributes to childhood malnutrition1–4. Here we analyse biospecimens from a randomized, controlled trial of a microbiome-directed complementary food (MDCF-2) that produced superior rates of weight gain compared with a calorically more dense conventional ready-to-use supplementary food in 12–18-month-old Bangladeshi children with moderate acute malnutrition4. We reconstructed 1,000 bacterial genomes (metagenome-assembled genomes (MAGs)) from the faecal microbiomes of trial participants, identified 75 MAGs of which the abundances were positively associated with ponderal growth (change in weight-for-length Z score (WLZ)), characterized changes in MAG gene expression as a function of treatment type and WLZ response, and quantified carbohydrate structures in MDCF-2 and faeces. The results reveal that two Prevotella copri MAGs that are positively associated with WLZ are the principal contributors to MDCF-2-induced expression of metabolic pathways involved in utilizing the component glycans of MDCF-2. The predicted specificities of carbohydrate-active enzymes expressed by their polysaccharide-utilization loci are correlated with (1) the in vitro growth of Bangladeshi P. copri strains, possessing varying degrees of polysaccharide-utilization loci and genomic conservation with these MAGs, in defined medium containing different purified glycans representative of those in MDCF-2, and (2) the levels of faecal carbohydrate structures in the trial participants. These associations suggest that identifying bioactive glycan structures in MDCFs metabolized by growth-associated bacterial taxa will help to guide recommendations about their use in children with acute malnutrition and enable the development of additional formulations.
Large-scale single-neuron speech sound encoding across the depth of human cortex
Authors: Leonard Matthew K. , Gwilliams Laura , Sellers Kristin K. , Chung Jason E. , Xu Duo , Mischler Gavin , Mesgarani Nima , Welkenhuysen Marleen , Dutta Barundeb , Chang Edward F. 
Published: December 2023

AbstractUnderstanding the neural basis of speech perception requires that we study the human brain both at the scale of the fundamental computational unit of neurons and in their organization across the depth of cortex. Here we used high-density Neuropixels arrays1–3 to record from 685 neurons across cortical layers at nine sites in a high-level auditory region that is critical for speech, the superior temporal gyrus4,5, while participants listened to spoken sentences. Single neurons encoded a wide range of speech sound cues, including features of consonants and vowels, relative vocal pitch, onsets, amplitude envelope and sequence statistics. Neurons at each cross-laminar recording exhibited dominant tuning to a primary speech feature while also containing a substantial proportion of neurons that encoded other features contributing to heterogeneous selectivity. Spatially, neurons at similar cortical depths tended to encode similar speech features. Activity across all cortical layers was predictive of high-frequency field potentials (electrocorticography), providing a neuronal origin for macroelectrode recordings from the cortical surface. Together, these results establish single-neuron tuning across the cortical laminae as an important dimension of speech encoding in human superior temporal gyrus.
The landscape of genomic structural variation in Indigenous Australians
Authors: Reis Andre L. M. , Rapadas Melissa , Hammond Jillian M. , Gamaarachchi Hasindu , Stevanovski Igor , Ayuputeri Kumaheri Meutia , Chintalaphani Sanjog R. , Dissanayake Duminda S. B. , Siggs Owen M. , Hewitt Alex W. , Llamas Bastien , Brown Alex , Baynam Gareth , Mann Graham J. , McMorran Brendan J. , Easteal Simon , Hermes Azure , Jenkins Misty R. ,   The National Centre for Indigenous Genomics, Pearson Glen , Roe Yvette , Mohamed Janine , Murray Ben , Ormond-Parker Lyndon , Kneipp Erica , Nugent Keith , Mann Graham , Patel Hardip R. , Deveson Ira W. 
Published: December 2023

AbstractIndigenous Australians harbour rich and unique genomic diversity. However, Aboriginal and Torres Strait Islander ancestries are historically under-represented in genomics research and almost completely missing from reference datasets1–3. Addressing this representation gap is critical, both to advance our understanding of global human genomic diversity and as a prerequisite for ensuring equitable outcomes in genomic medicine. Here we apply population-scale whole-genome long-read sequencing4 to profile genomic structural variation across four remote Indigenous communities. We uncover an abundance of large insertion–deletion variants (20–49 bp; n = 136,797), structural variants (50  b–50 kb; n = 159,912) and regions of variable copy number (>50 kb; n = 156). The majority of variants are composed of tandem repeat or interspersed mobile element sequences (up to 90%) and have not been previously annotated (up to 62%). A large fraction of structural variants appear to be exclusive to Indigenous Australians (12% lower-bound estimate) and most of these are found in only a single community, underscoring the need for broad and deep sampling to achieve a comprehensive catalogue of genomic structural variation across the Australian continent. Finally, we explore short tandem repeats throughout the genome to characterize allelic diversity at 50 known disease loci5, uncover hundreds of novel repeat expansion sites within protein-coding genes, and identify unique patterns of diversity and constraint among short tandem repeat sequences. Our study sheds new light on the dimensions and dynamics of genomic structural variation within and beyond Australia.
Modelling post-implantation human development to yolk sac blood emergence
Authors: Hislop Joshua , Song Qi , Keshavarz F. Kamyar , Alavi Amir , Schoenberger Rayna , LeGraw Ryan , Velazquez Jeremy J. , Mokhtari Tahere , Taheri Mohammad Naser , Rytel Matthew , Chuva de Sousa Lopes Susana M. , Watkins Simon , Stolz Donna , Kiani Samira , Sozen Berna , Bar-Joseph Ziv , Ebrahimkhani Mo R. 
Published: December 2023

AbstractImplantation of the human embryo begins a critical developmental stage that comprises profound events including axis formation, gastrulation and the emergence of haematopoietic system1,2. Our mechanistic knowledge of this window of human life remains limited due to restricted access to in vivo samples for both technical and ethical reasons3–5. Stem cell models of human embryo have emerged to help unlock the mysteries of this stage6–16. Here we present a genetically inducible stem cell-derived embryoid model of early post-implantation human embryogenesis that captures the reciprocal codevelopment of embryonic tissue and the extra-embryonic endoderm and mesoderm niche with early haematopoiesis. This model is produced from induced pluripotent stem cells and shows unanticipated self-organizing cellular programmes similar to those that occur in embryogenesis, including the formation of amniotic cavity and bilaminar disc morphologies as well as the generation of an anterior hypoblast pole and posterior domain. The extra-embryonic layer in these embryoids lacks trophoblast and shows advanced multilineage yolk sac tissue-like morphogenesis that harbours a process similar to distinct waves of haematopoiesis, including the emergence of erythroid-, megakaryocyte-, myeloid- and lymphoid-like cells. This model presents an easy-to-use, high-throughput, reproducible and scalable platform to probe multifaceted aspects of human development and blood formation at the early post-implantation stage. It will provide a tractable human-based model for drug testing and disease modelling.
GDF15 linked to maternal risk of nausea and vomiting during pregnancy
Authors: Fejzo M. , Rocha N. , Cimino I. , Lockhart S. M. , Petry C. J. , Kay R. G. , Burling K. , Barker P. , George A. L. , Yasara N. , Premawardhena A. , Gong S. , Cook E. , Rimmington D. , Rainbow K. , Withers D. J. , Cortessis V. , Mullin P. M. , MacGibbon K. W. , Jin E. , Kam A. , Campbell A. , Polasek O. , Tzoneva G. , Gribble F. M. , Yeo G. S. H. , Lam B. Y. H. , Saudek V. , Hughes I. A. , Ong K. K. , Perry J. R. B. , Sutton Cole A. , Baumgarten M. , Welsh P. , Sattar N. , Smith G. C. S. , Charnock-Jones D. S. , Coll A. P. , Meek C. L. , Mettananda S. , Hayward C. , Mancuso N. , O’Rahilly S. 
Published: December 2023

AbstractGDF15, a hormone acting on the brainstem, has been implicated in the nausea and vomiting of pregnancy, including its most severe form, hyperemesis gravidarum (HG), but a full mechanistic understanding is lacking1–4. Here we report that fetal production of GDF15 and maternal sensitivity to it both contribute substantially to the risk of HG. We confirmed that higher GDF15 levels in maternal blood are associated with vomiting in pregnancy and HG. Using mass spectrometry to detect a naturally labelled GDF15 variant, we demonstrate that the vast majority of GDF15 in the maternal plasma is derived from the feto-placental unit. By studying carriers of rare and common genetic variants, we found that low levels of GDF15 in the non-pregnant state increase the risk of developing HG. Conversely, women with β-thalassaemia, a condition in which GDF15 levels are chronically high5, report very low levels of nausea and vomiting of pregnancy. In mice, the acute food intake response to a bolus of GDF15 is influenced bi-directionally by prior levels of circulating GDF15 in a manner suggesting that this system is susceptible to desensitization. Our findings support a putative causal role for fetally derived GDF15 in the nausea and vomiting of human pregnancy, with maternal sensitivity, at least partly determined by prepregnancy exposure to the hormone, being a major influence on its severity. They also suggest mechanism-based approaches to the treatment and prevention of HG.
Response of Arctic benthic foraminiferal traits to past environmental changes
Authors: Hansen Katrine Elnegaard , Pearce Christof , Seidenkrantz Marit-Solveig 
Published: December 2023

AbstractThe Arctic is subjected to all-encompassing disruptions in marine ecosystems caused by anthropogenic warming. To provide reliable estimates of how future changes will affect the ecosystems, knowledge of Arctic marine ecosystem responses to past environmental variability beyond the instrumental era is essential. Here, we present a novel approach on how to evaluate the state of benthic marine biotic conditions during the deglacial and Holocene period on the Northeast Greenland shelf. Benthic foraminiferal species were assigned traits (e.g., oxygen tolerance, food preferences) aiming to identify past faunal changes as a response to external forcing mechanisms. This approach was applied on sediment cores from offshore Northeast Greenland. We performed numerical rate-of-change detection to determine significant changes in the benthic foraminiferal traits. That way, the significant abrupt trait changes can be assessed across sites, providing a better understanding of the impact of climate drivers on the traits. Our results demonstrate that during the last ~ 14,000 years, bottom water oxygen is the main factor affecting the variability in the benthic foraminiferal faunas in this area. Our results show that significant changes in the traits correspond to drastic climate perturbations. Specifically, the deglacial-Holocene transition and mid-Holocene warm period exhibited significant change, with several trait turnovers.
Molecular assessment of drug-phospholipid interactions consequent to cancer treatment: a study of anthracycline-induced cardiotoxicity
Authors: Ahmed Yara , Elkhodary Khalil I. , Youssef Mostafa 
Published: December 2023

AbstractCardiotoxicity limits the use of anthracyclines as potent chemotherapeutics. We employ classical molecular dynamics to explore anthracycline interactions with a realistic myocardial membrane and compare to an ideal membrane widely used in literature. The interaction of these two membranes with four anthracyclines; doxorubicin, epirubicin, daunorubicin, and idarubicin are studied. Careful analysis was conducted on three forms of each drug; pristine, primary metabolite, and cationic salt. By examining the molecular residence time near the membrane’s surface, the average number of molecule/membrane hydrogen bonds, the immobilization of the molecules near the membrane, and the location of those molecules relative to the mid-plane of the membrane we found out that salt forms exhibit the highest cardiotoxic probability, followed by the metabolites and pristine forms. Additionally, all forms have more affinity to the upper layer of the realistic myocardial membrane. Meanwhile, an ideal membrane consisting of a single type of phospholipids is not capable of capturing the specific interactions of each drug form. These findings confirm that cardiotoxic mechanisms are membrane-layer and drug-form dependent.
Pupil responses to colorfulness are selectively reduced in healthy older adults
Authors: van Leeuwen Janneke E. P. , McDougall Amy , Mylonas Dimitris , Suárez-González Aida , Crutch Sebastian J. , Warren Jason D. 
Published: December 2023

AbstractThe alignment between visual pathway signaling and pupil dynamics offers a promising non-invasive method to further illuminate the mechanisms of human color perception. However, only limited research has been done in this area and the effects of healthy aging on pupil responses to the different color components have not been studied yet. Here we aim to address this by modelling the effects of color lightness and chroma (colorfulness) on pupil responses in young and older adults, in a closely controlled passive viewing experiment with 26 broad-spectrum digital color fields. We show that pupil responses to color lightness and chroma are independent from each other in both young and older adults. Pupil responses to color lightness levels are unaffected by healthy aging, when correcting for smaller baseline pupil sizes in older adults. Older adults exhibit weaker pupil responses to chroma increases, predominantly along the Green–Magenta axis, while relatively sparing the Blue–Yellow axis. Our findings complement behavioral studies in providing physiological evidence that colors fade with age, with implications for color-based applications and interventions both in healthy aging and later-life neurodegenerative disorders.