RESUMEN
BACKGROUND: Spinal intradural tumors are rare and heterogeneous in histological type, aggressiveness, and symptomatology, and there is a lack of data about them. This study investigated the epidemiological features of spinal intradural tumors. METHODS: This retrospective analysis included patients with spinal intradural tumors who underwent surgical treatment at the Myelopathy and Spondylosis Ward Beijing Jishuitan Hospital between January 2012 and December 2022. RESULTS: This study included 1321 patients [aged 47.19 ± 14.90 years, 603 (45.65%) males] with spinal intradural tumors. The most common histological subtype was schwannoma [n = 511 (38.68%)], followed by spinal meningioma [n = 184 (13.93%)] and ependymoma [n = 101 (7.65%)]. Fifteen (1.14%) patients were diagnosed with metastatic spinal intradural tumors as a presentation of another primary cancer type. The spinal intradural tumors were mostly found in the lumbar region [n = 436 (33.01%)], followed by the thoracic vertebrae [n = 390 (29.52%)], cervical vertebrae [n = 154 (11.66%)], and thoracolumbar region [n = 111 (8.40%)]. Schwannomas mostly affected the lumbar region [n = 256 (52.64%)], spinal meningiomas in the thoracic region [n = 153 (83.15)], and ependymomas in the lumbar region [56 (55.45%)]. The de novo metastases were mostly found in the lumbar region [n = 8 (53.33%)]. CONCLUSION: According to the results of our single-center study, the most common spinal intradural tumor in Northern China is schwannoma, followed by spinal meningioma and ependymoma.
Asunto(s)
Ependimoma , Meningioma , Neurilemoma , Neoplasias de la Médula Espinal , Humanos , Masculino , Persona de Mediana Edad , Femenino , Estudios Retrospectivos , Adulto , Neoplasias de la Médula Espinal/epidemiología , Neoplasias de la Médula Espinal/cirugía , Ependimoma/epidemiología , Ependimoma/cirugía , Ependimoma/patología , Anciano , Meningioma/epidemiología , Meningioma/cirugía , Meningioma/patología , Beijing/epidemiología , Neurilemoma/epidemiología , Neurilemoma/cirugía , Neurilemoma/patología , Adulto Joven , Vértebras Cervicales/cirugía , Vértebras Cervicales/patología , Neoplasias Meníngeas/epidemiología , Neoplasias Meníngeas/cirugía , Neoplasias Meníngeas/patología , Adolescente , Anciano de 80 o más Años , Vértebras Torácicas/cirugía , Vértebras Torácicas/patologíaRESUMEN
The completion of the Human Genome Project has provided a foundational blueprint for understanding human life. Nonetheless, understanding the intricate mechanisms through which our genetic blueprint is involved in disease or orchestrates development across temporal and spatial dimensions remains a profound scientific challenge. Recent breakthroughs in cellular omics technologies have paved new pathways for understanding the regulation of genomic elements and the relationship between gene expression, cellular functions, and cell fate determination. The advent of spatial omics technologies, encompassing both imaging and sequencing-based methodologies, has enabled a comprehensive understanding of biological processes from a cellular ecosystem perspective. This review offers an updated overview of how spatial omics has advanced our understanding of the translation of genetic information into cellular heterogeneity and tissue structural organization and their dynamic changes over time. It emphasizes the discovery of various biological phenomena, related to organ functionality, embryogenesis, species evolution, and the pathogenesis of diseases.
Asunto(s)
Genómica , Humanos , Animales , ProteómicaRESUMEN
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.
Asunto(s)
Cromatina , Células Madre Pluripotentes , Análisis de la Célula Individual , Teratoma , Humanos , Teratoma/genética , Teratoma/patología , Células Madre Pluripotentes/metabolismo , Linaje de la Célula , Factores de Transcripción/genéticaRESUMEN
Aneuploidy is frequently detected in early human embryos as a major cause of early pregnancy failure. However, how aneuploidy affects cellular function remains elusive. Here, we profiled the transcriptomes of 14,908 single cells from 203 human euploid and aneuploid blastocysts involving autosomal and sex chromosomes. Nearly all of the blastocysts contained four lineages. In aneuploid chromosomes, 19.5% ± 1.2% of the expressed genes showed a dosage effect, and 90 dosage-sensitive domains were identified. Aneuploidy leads to prevalent genome-wide transcriptome alterations. Common effects, including apoptosis, were identified, especially in monosomies, partially explaining the lower cell numbers in autosomal monosomies. We further identified lineage-specific effects causing unstable epiblast development in aneuploidies, which was accompanied by the downregulation of TGF-ß and FGF signaling, which resulted in insufficient trophectoderm maturation. Our work provides crucial insights into the molecular basis of human aneuploid blastocysts and may shed light on the cellular interaction during blastocyst development.
Asunto(s)
Aneuploidia , Blastocisto , Análisis de la Célula Individual , Transcriptoma , Humanos , Blastocisto/metabolismo , Blastocisto/citología , Análisis de la Célula Individual/métodos , Femenino , Regulación del Desarrollo de la Expresión Génica , Desarrollo Embrionario/genética , Perfilación de la Expresión Génica/métodos , Embarazo , Transducción de Señal/genética , Apoptosis/genética , Factor de Crecimiento Transformador beta/metabolismo , Factor de Crecimiento Transformador beta/genética , Linaje de la Célula/genéticaRESUMEN
Non-coding RNAs (ncRNAs) play essential regulatory functions in various physiological and pathological processes in the brain. To systematically characterize the ncRNA profile in cortical cells, we downloaded single-cell SMART-Seq v4 data of mouse cerebral cortex. Our results revealed that the ncRNAs alone are sufficient to define the identity of most cortical cell types. We identified 1,600 ncRNAs that exhibited cell type specificity, even yielding to distinguish microglia from perivascular macrophages with ncRNA. Moreover, we characterized cortical layer and region specific ncRNAs, in line with the results by spatial transcriptome (ST) data. By constructing a co-expression network of ncRNAs and protein-coding genes, we predicted the function of ncRNAs. By integrating with genome-wide association studies data, we established associations between cell type-specific ncRNAs and traits related to neurological disorders. Collectively, our study identified differentially expressed ncRNAs at multiple levels and provided the valuable resource to explore the functions and dysfunctions of ncRNAs in cortical cells.
RESUMEN
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 TGFß 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.
Asunto(s)
Colestasis , Hepatocitos , Animales , Ratones , Colestasis/genética , Colestasis/patología , Colestasis/metabolismo , Hepatocitos/metabolismo , Hígado/metabolismo , Hígado/lesiones , Hígado/patología , Proliferación Celular/genética , Conductos Biliares/metabolismo , Regeneración Hepática/genética , Ratones Endogámicos C57BL , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Transducción de Señal , Masculino , Factor de Crecimiento Transformador beta/metabolismo , Factor de Crecimiento Transformador beta/genética , Transcriptoma , Modelos Animales de Enfermedad , Análisis Espacio-TemporalRESUMEN
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.
Asunto(s)
Envejecimiento , Músculo Esquelético , Análisis de la Célula Individual , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Envejecimiento/genética , Envejecimiento/patología , Envejecimiento/fisiología , Núcleo Celular/metabolismo , Cromatina/metabolismo , Cromatina/genética , Susceptibilidad a Enfermedades , Epigénesis Genética , Fragilidad/genética , Fragilidad/patología , Músculo Esquelético/citología , Músculo Esquelético/metabolismo , Músculo Esquelético/patología , Atrofia Muscular/genética , Atrofia Muscular/patología , Sarcopenia/genética , Sarcopenia/patología , TranscriptomaRESUMEN
BACKGROUND: Coinfection of human immunodeficiency virus type 1 (HIV-1) is the most significant risk factor for tuberculosis (TB). The immune responses of the lung are essential to restrict the growth of Mycobacterium tuberculosis and avoid the emergence of the disease. Nevertheless, there is still limited knowledge about the local immune response in people with HIV-1-TB coinfection. METHODS: We employed single-cell RNA sequencing (scRNA-seq) on bronchoalveolar lavage fluid from 9 individuals with HIV-1-TB coinfection and 10 with pulmonary TB. RESULTS: A total of 19 058 cells were grouped into 4 major cell types: myeloid cells, T/natural killer (NK) cells, B cells, and epithelial cells. The myeloid cells and T/NK cells were further divided into 10 and 11 subsets, respectively. The proportions of dendritic cell subsets, CD4+ T cells, and NK cells were lower in the HIV-1-TB coinfection group compared to the TB group, while the frequency of CD8+ T cells was higher. Additionally, we identified numerous differentially expressed genes between the CD4+ and CD8+ T-cell subsets between the 2 groups. CONCLUSIONS: HIV-1 infection not only affects the abundance of immune cells in the lungs but also alters their functions in patients with pulmonary TB.
RESUMEN
The hypothalamus plays a crucial role in the progression of obesity and diabetes; however, its structural complexity and cellular heterogeneity impede targeted treatments. Here, we profiled the single-cell and spatial transcriptome of the hypothalamus in obese and sporadic type 2 diabetic macaques, revealing primate-specific distributions of clusters and genes as well as spatial region, cell-type-, and gene-feature-specific changes. The infundibular (INF) and paraventricular nuclei (PVN) are most susceptible to metabolic disruption, with the PVN being more sensitive to diabetes. In the INF, obesity results in reduced synaptic plasticity and energy sensing capability, whereas diabetes involves molecular reprogramming associated with impaired tanycytic barriers, activated microglia, and neuronal inflammatory response. In the PVN, cellular metabolism and neural activity are suppressed in diabetic macaques. Spatial transcriptomic data reveal microglia's preference for the parenchyma over the third ventricle in diabetes. Our findings provide a comprehensive view of molecular changes associated with obesity and diabetes.
Asunto(s)
Diabetes Mellitus , Núcleo Hipotalámico Paraventricular , Animales , Núcleo Hipotalámico Paraventricular/metabolismo , Transcriptoma/genética , Hipotálamo/metabolismo , Obesidad/metabolismo , Diabetes Mellitus/metabolismo , Perfilación de la Expresión GénicaRESUMEN
Optimal integration of transcriptomics data and associated spatial information is essential towards fully exploiting spatial transcriptomics to dissect tissue heterogeneity and map out inter-cellular communications. We present SEDR, which uses a deep autoencoder coupled with a masked self-supervised learning mechanism to construct a low-dimensional latent representation of gene expression, which is then simultaneously embedded with the corresponding spatial information through a variational graph autoencoder. SEDR achieved higher clustering performance on manually annotated 10 × Visium datasets and better scalability on high-resolution spatial transcriptomics datasets than existing methods. Additionally, we show SEDR's ability to impute and denoise gene expression (URL: https://github.com/JinmiaoChenLab/SEDR/ ).
Asunto(s)
Comunicación Celular , Perfilación de la Expresión Génica , Humanos , Análisis por ConglomeradosRESUMEN
Onco-fetal reprogramming of the tumor ecosystem induces fetal developmental signatures in the tumor microenvironment, leading to immunosuppressive features. Here, we employed single-cell RNA sequencing, spatial transcriptomics and bulk RNA sequencing to delineate specific cell subsets involved in hepatocellular carcinoma (HCC) relapse and response to immunotherapy. We identified POSTN+ extracellular matrix cancer-associated fibroblasts (EM CAFs) as a prominent onco-fetal interacting hub, promoting tumor progression. Cell-cell communication and spatial transcriptomics analysis revealed crosstalk and co-localization of onco-fetal cells, including POSTN+ CAFs, FOLR2+ macrophages and PLVAP+ endothelial cells. Further analyses suggest an association between onco-fetal reprogramming and epithelial-mesenchymal transition (EMT), tumor cell proliferation and recruitment of Treg cells, ultimately influencing early relapse and response to immunotherapy. In summary, our study identifies POSTN+ CAFs as part of the HCC onco-fetal niche and highlights its potential influence in EMT, relapse and immunotherapy response, paving the way for the use of onco-fetal signatures for therapeutic stratification.
Asunto(s)
Carcinoma Hepatocelular , Receptor 2 de Folato , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/genética , Ecosistema , Células Endoteliales , Movimiento Celular/genética , Enfermedad Crónica , Recurrencia , Inmunoterapia , Microambiente Tumoral/genéticaRESUMEN
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.
Asunto(s)
Células Madre Pluripotentes , Factores de Transcripción , Embarazo , Femenino , Humanos , Ratones , Animales , Linaje de la Célula/genética , Factores de Transcripción/genética , Trofoblastos/fisiología , Diferenciación Celular/genética , Mamíferos , Primates , Proteínas de Unión al ADN/genética , Factores de Transcripción de Dominio TEARESUMEN
Recent technological developments in spatial transcriptomics allow researchers to measure gene expression of cells and their spatial locations at the single-cell level, generating detailed biological insight into biological processes. A comprehensive database could facilitate the sharing of spatial transcriptomic data and streamline the data acquisition process for researchers. Here, we present the Spatial TranscriptOmics DataBase (STOmicsDB), a database that serves as a one-stop hub for spatial transcriptomics. STOmicsDB integrates 218 manually curated datasets representing 17 species. We annotated cell types, identified spatial regions and genes, and performed cell-cell interaction analysis for these datasets. STOmicsDB features a user-friendly interface for the rapid visualization of millions of cells. To further facilitate the reusability and interoperability of spatial transcriptomic data, we developed standards for spatial transcriptomic data archiving and constructed a spatial transcriptomic data archiving system. Additionally, we offer a distinctive capability of customizing dedicated sub-databases in STOmicsDB for researchers, assisting them in visualizing their spatial transcriptomic analyses. We believe that STOmicsDB could contribute to research insights in the spatial transcriptomics field, including data archiving, sharing, visualization and analysis. STOmicsDB is freely accessible at https://db.cngb.org/stomics/.
Asunto(s)
Bases de Datos Genéticas , Perfilación de la Expresión Génica , Transcriptoma , Difusión de la InformaciónRESUMEN
Human cancer cell lines have long served as tools for cancer research and drug discovery, but the presence and the source of intra-cell-line heterogeneity remain elusive. Here, we perform single-cell RNA-sequencing and ATAC-sequencing on 42 and 39 human cell lines, respectively, to illustrate both transcriptomic and epigenetic heterogeneity within individual cell lines. Our data reveal that transcriptomic heterogeneity is frequently observed in cancer cell lines of different tissue origins, often driven by multiple common transcriptional programs. Copy number variation, as well as epigenetic variation and extrachromosomal DNA distribution all contribute to the detected intra-cell-line heterogeneity. Using hypoxia treatment as an example, we demonstrate that transcriptomic heterogeneity could be reshaped by environmental stress. Overall, our study performs single-cell multi-omics of commonly used human cancer cell lines and offers mechanistic insights into the intra-cell-line heterogeneity and its dynamics, which would serve as an important resource for future cancer cell line-based studies.
Asunto(s)
Variaciones en el Número de Copia de ADN , Neoplasias , Humanos , Multiómica , Línea Celular Tumoral , Epigenómica , Transcriptoma , Neoplasias/genéticaRESUMEN
As a major neuron type in the brain, the excitatory neuron (EN) regulates the lifespan in C. elegans. How the EN acquires senescence, however, is unknown. Here, we show that growth differentiation factor 11 (GDF11) is predominantly expressed in the EN in the adult mouse, marmoset and human brain. In mice, selective knock-out of GDF11 in the post-mitotic EN shapes the brain ageing-related transcriptional profile, induces EN senescence and hyperexcitability, prunes their dendrites, impedes their synaptic input, impairs object recognition memory and shortens the lifespan, establishing a functional link between GDF11, brain ageing and cognition. In vitro GDF11 deletion causes cellular senescence in Neuro-2a cells. Mechanistically, GDF11 deletion induces neuronal senescence via Smad2-induced transcription of the pro-senescence factor p21. This work indicates that endogenous GDF11 acts as a brake on EN senescence and brain ageing.
Asunto(s)
Caenorhabditis elegans , Factores de Diferenciación de Crecimiento , Adulto , Ratones , Humanos , Animales , Caenorhabditis elegans/metabolismo , Factores de Diferenciación de Crecimiento/genética , Factores de Diferenciación de Crecimiento/metabolismo , Envejecimiento/genética , Encéfalo/metabolismo , Neuronas/metabolismo , Proteínas Morfogenéticas ÓseasRESUMEN
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.
Asunto(s)
Células Madre Embrionarias , Ingeniería Genética , Haplorrinos , Animales , Femenino , Embarazo , Haplorrinos/genética , Nacimiento Vivo , Mamíferos , Células Madre Pluripotentes , Primates , Ingeniería Genética/métodosRESUMEN
Axolotl (Ambystoma mexicanum) is an excellent model for investigating regeneration, the interaction between regenerative and developmental processes, comparative genomics, and evolution. The brain, which serves as the material basis of consciousness, learning, memory, and behavior, is the most complex and advanced organ in axolotl. The modulation of transcription factors is a crucial aspect in determining the function of diverse regions within the brain. There is, however, no comprehensive understanding of the gene regulatory network of axolotl brain regions. Here, we utilized single-cell ATAC sequencing to generate the chromatin accessibility landscapes of 81,199 cells from the olfactory bulb, telencephalon, diencephalon and mesencephalon, hypothalamus and pituitary, and the rhombencephalon. Based on these data, we identified key transcription factors specific to distinct cell types and compared cell type functions across brain regions. Our results provide a foundation for comprehensive analysis of gene regulatory programs, which are valuable for future studies of axolotl brain development, regeneration, and evolution, as well as on the mechanisms underlying cell-type diversity in vertebrate brains.
Asunto(s)
Ambystoma mexicanum , Encéfalo , Cromatina , Animales , Ambystoma mexicanum/genética , Ascomicetos , Aprendizaje , Mesencéfalo , Análisis de Expresión Génica de una Sola CélulaRESUMEN
Cell-cell interaction is one of the major modalities for transmitting information between cells and activating the effects of functional cells. However, the construction of high-throughput analysis technologies from cell omics focusing on the impact of interactions of functional cells on targets has been relatively unexplored. Here, they propose a droplet-based microfluidic platform for cell-cell interaction sequencing (c-c-seq) and screening in vitro to address this challenge. A class of interacting cells is pre-labeled using cell molecular tags, and additional single-cell sequencing reagents are introduced to quickly form functional droplet mixes. Lastly, gene expression analysis is used to deduce the impact of the interaction, while molecular sequence tracing identifies the type of interaction. Research into the active effect between antigen-presenting cells and T cells, one of the most common cell-to-cell interactions, is crucial for the advancement of cancer therapy, particularly T cell receptor-engineered T cell therapy. As it allows for high throughput, this platform is superior to well plates as a research platform for cell-to-cell interactions. When combined with the next generation of sequencing, the platform may be able to more accurately evaluate interactions between epitopes and receptors and verify their functional relevance.
Asunto(s)
Microfluídica , Transcriptoma , Transcriptoma/genética , Perfilación de la Expresión Génica , Receptores de Antígenos de Linfocitos T/metabolismo , Linfocitos T/metabolismoRESUMEN
Vertebrate embryogenesis is a remarkable process, during which numerous cell types of different lineages arise within a short time frame. An overwhelming challenge to understand this process is the lack of dynamic chromatin accessibility information to correlate cis-regulatory elements (CREs) and gene expression within the hierarchy of cell fate decisions. Here, we employed single-nucleus ATAC-seq to generate a chromatin accessibility dataset on the first day of zebrafish embryogenesis, including 3.3 hpf, 5.25 hpf, 6 hpf, 10 hpf, 12 hpf, 18 hpf and 24 hpf, obtained 51,620 high-quality nuclei and 23 clusters. Furthermore, by integrating snATAC-seq data with single-cell RNA-seq data, we described the dynamics of chromatin accessibility and gene expression across developmental time points, which validates the accuracy of the chromatin landscape data. Together, our data could serve as a fundamental resource for revealing the epigenetic regulatory mechanisms of zebrafish embryogenesis.
Asunto(s)
Cromatina , Pez Cebra , Animales , Diferenciación Celular/genética , Núcleo Celular/metabolismo , Cromatina/genética , Cromatina/metabolismo , Desarrollo Embrionario/genética , Pez Cebra/genética , Pez Cebra/metabolismoRESUMEN
In mammals, early organogenesis begins soon after gastrulation, accompanied by specification of various type of progenitor/precusor cells. In order to reveal dynamic chromatin landscape of precursor cells and decipher the underlying molecular mechanism driving early mouse organogenesis, we performed single-cell ATAC-seq of E8.5-E10.5 mouse embryos. We profiled a total of 101,599 single cells and identified 41 specific cell types at these stages. Besides, by performing integrated analysis of scATAC-seq and public scRNA-seq data, we identified the critical cis-regulatory elements and key transcription factors which drving development of spinal cord and somitogenesis. Furthermore, we intersected accessible peaks with human diseases/traits-related loci and found potential clinical associated single nucleotide variants (SNPs). Overall, our work provides a fundamental source for understanding cell fate determination and revealing the underlying mechanism during postimplantation embryonic development, and expand our knowledge of pathology for human developmental malformations.