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1.
Sci Data ; 11(1): 574, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38834597

RESUMO

Experts from 18 consortia are collaborating on the Human Reference Atlas (HRA) which aims to map the 37 trillion cells in the healthy human body. Information relevant for HRA construction and usage is held by experts, published in scholarly papers, and captured in experimental data. However, these data sources use different metadata schemas and cannot be cross-searched efficiently. This paper documents the compilation of a dataset, named HRAlit, that links the 136 HRA v1.4 digital objects (31 organs with 4,279 anatomical structures, 1,210 cell types, 2,089 biomarkers) to 583,117 experts; 7,103,180 publications; 896,680 funded projects, and 1,816 experimental datasets. The resulting HRAlit has 22 tables with 20,939,937 records including 6 junction tables with 13,170,651 relationships. The HRAlit can be mined to identify leading experts, major papers, funding trends, or alignment with existing ontologies in support of systematic HRA construction and usage.


Assuntos
Células , Metadados , Humanos
3.
Nature ; 630(8018): 943-949, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38898271

RESUMO

Spatial transcriptomics measures in situ gene expression at millions of locations within a tissue1, hitherto with some trade-off between transcriptome depth, spatial resolution and sample size2. Although integration of image-based segmentation has enabled impactful work in this context, it is limited by imaging quality and tissue heterogeneity. By contrast, recent array-based technologies offer the ability to measure the entire transcriptome at subcellular resolution across large samples3-6. Presently, there exist no approaches for cell type identification that directly leverage this information to annotate individual cells. Here we propose a multiscale approach to automatically classify cell types at this subcellular level, using both transcriptomic information and spatial context. We showcase this on both targeted and whole-transcriptome spatial platforms, improving cell classification and morphology for human kidney tissue and pinpointing individual sparsely distributed renal mouse immune cells without reliance on image data. By integrating these predictions into a topological pipeline based on multiparameter persistent homology7-9, we identify cell spatial relationships characteristic of a mouse model of lupus nephritis, which we validate experimentally by immunofluorescence. The proposed framework readily generalizes to new platforms, providing a comprehensive pipeline bridging different levels of biological organization from genes through to tissues.


Assuntos
Células , Perfilação da Expressão Gênica , Espaço Intracelular , Rim , Transcriptoma , Animais , Feminino , Humanos , Camundongos , Células/classificação , Células/metabolismo , Modelos Animais de Doenças , Imunofluorescência , Perfilação da Expressão Gênica/métodos , Rim/citologia , Rim/imunologia , Rim/metabolismo , Rim/patologia , Nefrite Lúpica/genética , Nefrite Lúpica/imunologia , Nefrite Lúpica/metabolismo , Nefrite Lúpica/patologia , Reprodutibilidade dos Testes , Espaço Intracelular/genética , Espaço Intracelular/metabolismo
5.
Nature ; 629(8010): 193-200, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38600383

RESUMO

Sex differences in mammalian complex traits are prevalent and are intimately associated with androgens1-7. However, a molecular and cellular profile of sex differences and their modulation by androgens is still lacking. Here we constructed a high-dimensional single-cell transcriptomic atlas comprising over 2.3 million cells from 17 tissues in Mus musculus and explored the effects of sex and androgens on the molecular programs and cellular populations. In particular, we found that sex-biased immune gene expression and immune cell populations, such as group 2 innate lymphoid cells, were modulated by androgens. Integration with the UK Biobank dataset revealed potential cellular targets and risk gene enrichment in antigen presentation for sex-biased diseases. This study lays the groundwork for understanding the sex differences orchestrated by androgens and provides important evidence for targeting the androgen pathway as a broad therapeutic strategy for sex-biased diseases.


Assuntos
Androgênios , Células , Caracteres Sexuais , Análise de Célula Única , Transcriptoma , Animais , Feminino , Humanos , Masculino , Camundongos , Androgênios/metabolismo , Androgênios/farmacologia , Apresentação de Antígeno/efeitos dos fármacos , Apresentação de Antígeno/genética , Imunidade Inata , Linfócitos/metabolismo , Linfócitos/citologia , Linfócitos/imunologia , Linfócitos/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Transcriptoma/efeitos dos fármacos , Transcriptoma/genética , Biobanco do Reino Unido , Células/efeitos dos fármacos , Células/imunologia , Células/metabolismo
6.
Nature ; 628(8006): 47-56, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38570716

RESUMO

Most life scientists would agree that understanding how cellular processes work requires structural knowledge about the macromolecules involved. For example, deciphering the double-helical nature of DNA revealed essential aspects of how genetic information is stored, copied and repaired. Yet, being reductionist in nature, structural biology requires the purification of large amounts of macromolecules, often trimmed off larger functional units. The advent of cryogenic electron microscopy (cryo-EM) greatly facilitated the study of large, functional complexes and generally of samples that are hard to express, purify and/or crystallize. Nevertheless, cryo-EM still requires purification and thus visualization outside of the natural context in which macromolecules operate and coexist. Conversely, cell biologists have been imaging cells using a number of fast-evolving techniques that keep expanding their spatial and temporal reach, but always far from the resolution at which chemistry can be understood. Thus, structural and cell biology provide complementary, yet unconnected visions of the inner workings of cells. Here we discuss how the interplay between cryo-EM and cryo-electron tomography, as a connecting bridge to visualize macromolecules in situ, holds great promise to create comprehensive structural depictions of macromolecules as they interact in complex mixtures or, ultimately, inside the cell itself.


Assuntos
Biologia Celular , Células , Microscopia Crioeletrônica , Tomografia com Microscopia Eletrônica , Microscopia Crioeletrônica/métodos , Microscopia Crioeletrônica/tendências , Tomografia com Microscopia Eletrônica/métodos , Tomografia com Microscopia Eletrônica/tendências , Substâncias Macromoleculares/análise , Substâncias Macromoleculares/química , Substâncias Macromoleculares/metabolismo , Substâncias Macromoleculares/ultraestrutura , Biologia Celular/instrumentação , Células/química , Células/citologia , Células/metabolismo , Células/ultraestrutura , Humanos
9.
Med. oral patol. oral cir. bucal (Internet) ; 29(2): e288-e296, Mar. 2024. tab, ilus
Artigo em Inglês | IBECS | ID: ibc-231233

RESUMO

Background: Collagen is a component of Pyogenic Granuloma (PG) and Peripheral Ossifying Fibroma (POF) and performs different functions in these lesions. The objective of this study is to evaluate the role of collagen and immunostaining for Transforming Growth Factor beta (TGF-β) in the clinical and microscopic findings of PG and POF. Material and Methods: PG (n=20) and POF (n=20) were selected for clinical evaluation (sex, age, localization, size and evolution time) and microscopic analysis (picrosirius red staining for collagen analysis and immunohistochemistry for TGF-β) performed in the superficial and deep areas of the two lesions. ANOVA/Bonferroni and t-test, Pearson correlation and χ2 were used to compare the sites and parameters analyzed (p<0.05, GraphPad Prism 5.0). Results: The depth of PG presented the highest amount of collagen (p<0.001), and its surface showed the lowest amount of type 1 collagen (yellow-red strong birefringence). Type 1 collagen gradually increased in depth of PG, surface and depth of POF (p<0.001). The number of TGF-β+ cells was lower on the surface of PG compared with the depth of PG and the two areas of POF (p<0.001). Sex and localization did not affect these parameters, but the profile of collagen and immunostaining for TGF-β suffered from modifications by the time of evolution and the size of the lesion. Conclusions: Although PG and POF are reactive gingival lesions, the expression of TGF-β and its role in collagen showed different biological behaviors in these lesions, suggesting different biological origins for its components. (AU)


Assuntos
Humanos , Colágeno , Fibroma Ossificante , Sexo , Ferimentos e Lesões , Células
10.
Science ; 383(6685): 890-897, 2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38386755

RESUMO

Recordings of the physiological history of cells provide insights into biological processes, yet obtaining such recordings is a challenge. To address this, we introduce a method to record transient cellular events for later analysis. We designed proteins that become labeled in the presence of both a specific cellular activity and a fluorescent substrate. The recording period is set by the presence of the substrate, whereas the cellular activity controls the degree of the labeling. The use of distinguishable substrates enabled the recording of successive periods of activity. We recorded protein-protein interactions, G protein-coupled receptor activation, and increases in intracellular calcium. Recordings of elevated calcium levels allowed selections of cells from heterogeneous populations for transcriptomic analysis and tracking of neuronal activities in flies and zebrafish.


Assuntos
Cálcio , Fenômenos Fisiológicos Celulares , Células , Coloração e Rotulagem , Animais , Corantes , Perfilação da Expressão Gênica , Peixe-Zebra , Células/química , Domínios e Motivos de Interação entre Proteínas
11.
Physiology (Bethesda) ; 39(3): 0, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38319138

RESUMO

The application of single-cell molecular profiling coupled with spatial technologies has enabled charting of cellular heterogeneity in reference tissues and in disease. This new wave of molecular data has highlighted the expected diversity of single-cell dynamics upon shared external queues and spatial organizations. However, little is known about the relationship between single-cell heterogeneity and the emergence and maintenance of robust multicellular processes in developed tissues and its role in (patho)physiology. Here, we present emerging computational modeling strategies that use increasingly available large-scale cross-condition single-cell and spatial datasets to study multicellular organization in tissues and complement cell taxonomies. This perspective should enable us to better understand how cells within tissues collectively process information and adapt synchronized responses in disease contexts and to bridge the gap between structural changes and functions in tissues.


Assuntos
Células , Tecidos , Tecidos/citologia
12.
Small ; 20(24): e2306725, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38287726

RESUMO

Droplet microfluidics are extensively utilized to generate monodisperse cell-laden microgels in biomedical applications. However, maintaining cell viability is still challenging due to overexposure to harsh conditions in subsequent procedures that recover the microgels from the oil phase. Here, a gravity-oriented microfluidic device for end-to-end fabrication of cell-laden microgels is reported, which integrates dispersion, gelation, and extraction into a continuous workflow. This innovative on-chip extraction, driven by native buoyancy and kinetically facilitated by pseudosurfactant, exhibits 100% retrieval efficiency for microgels with a wide range of sizes and stiffnesses. The viability of encapsulated cells is perfectly maintained at ≈98% with minimal variations within and between batches. The end-to-end fabrication remarkably enhances the biocompatibility and practicality of microfluidics-based cell encapsulation and is promising to be compatible with various applications ranging from single-cell analysis to clinical therapy.


Assuntos
Materiais Biocompatíveis , Células , Dispositivos Lab-On-A-Chip , Microgéis , Microgéis/química , Dispositivos Lab-On-A-Chip/normas , Gravitação , Células/química
13.
Nature ; 626(7997): 212-220, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38086419

RESUMO

Transcriptional enhancers act as docking stations for combinations of transcription factors and thereby regulate spatiotemporal activation of their target genes1. It has been a long-standing goal in the field to decode the regulatory logic of an enhancer and to understand the details of how spatiotemporal gene expression is encoded in an enhancer sequence. Here we show that deep learning models2-6, can be used to efficiently design synthetic, cell-type-specific enhancers, starting from random sequences, and that this optimization process allows detailed tracing of enhancer features at single-nucleotide resolution. We evaluate the function of fully synthetic enhancers to specifically target Kenyon cells or glial cells in the fruit fly brain using transgenic animals. We further exploit enhancer design to create 'dual-code' enhancers that target two cell types and minimal enhancers smaller than 50 base pairs that are fully functional. By examining the state space searches towards local optima, we characterize enhancer codes through the strength, combination and arrangement of transcription factor activator and transcription factor repressor motifs. Finally, we apply the same strategies to successfully design human enhancers, which adhere to enhancer rules similar to those of Drosophila enhancers. Enhancer design guided by deep learning leads to better understanding of how enhancers work and shows that their code can be exploited to manipulate cell states.


Assuntos
Células , Aprendizado Profundo , Drosophila melanogaster , Elementos Facilitadores Genéticos , Biologia Sintética , Animais , Humanos , Animais Geneticamente Modificados/genética , Elementos Facilitadores Genéticos/genética , Regulação da Expressão Gênica , Fatores de Transcrição/metabolismo , Células/classificação , Células/metabolismo , Neuroglia/metabolismo , Encéfalo/citologia , Drosophila melanogaster/citologia , Drosophila melanogaster/genética , Proteínas Repressoras/metabolismo
14.
Braz. J. Pharm. Sci. (Online) ; 60: e23380, 2024. graf
Artigo em Inglês | LILACS | ID: biblio-1533983

RESUMO

Abstract Glioblastoma multiforme is a tumor of the central nervous system. Focal Adhesion Kinase (FAK) and αB-crystalline are two proteins involved in glioblastoma development. In this study, we investigated whether the FAK/αB-crystalline interaction is important for glioblastoma cells, we aimed to investigate the interaction of these two proteins in the glioblastoma multiforme cell line U87-MG. Two peptides named FP01 peptide (derived from αB-crystalline) and FP02 peptide (derived from FAK) were synthesized for this study. Treatment of U87-MG with the peptides FP01 and FP02 in the concentration at 50 µM reduced the viability cellular to around 41% and 51%, respectively. Morphological alterations in the cells treated with the peptides when compared to the control were observed. This study suggests that the interaction between FAK and αB-crystalline is important for the viability of glioblastoma cells


Assuntos
Peptídeos/efeitos adversos , Células/classificação , Glioblastoma/patologia , Proteína-Tirosina Quinases de Adesão Focal/efeitos adversos , Neoplasias/patologia , Linhagem Celular/classificação , Sistema Nervoso Central/anormalidades
15.
J Biomech ; 162: 111909, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38118308

RESUMO

The properties of organs, tissues, organoids, and other systems of cells, are influenced by the spatial localization and distribution of their elements. Here, we used networks to describe distributions of cells on a surface where the small-world coefficient (SW) of the networks was varied between SW~1 (random uniform distributions) and SW~10 (clustered distributions). The small-world coefficient is a topological measure of graphs: networks with SW>1 are topologically biased to transmit information. For each system configuration, we then determined the total energy U as the sum of the energies that describe cell-cell interactions - approximated by a harmonic potential. The graph of energy (U) across the configuration space of the networks (SW) is the energy landscape: it indicates which configuration a system of cells will likely assume over time. We found that, depending on the model parameters, the energy landscapes of 2D distributions of cells may be of different types: from type I to type IV. Type I and type II systems have high probability to evolve into random distributions. Type III and type IV systems have a higher probability to form clustered architectures. A great many of simulations indicated that cultures of cells with high initial density and limited sensing range could evolve into clustered configurations with enhanced topological characteristics. Moreover, the strongest the binding between cells, the greater the likelihood that they will assume configurations characterized by finite values of SW. Results of the work are relevant for those working the field of tissue engineering, regenerative medicine, the formation of in-vitro-models, the analysis of neuro-degenerative diseases.


Assuntos
Células , Metabolismo Energético , Células/metabolismo
16.
Braz. j. oral sci ; 23: e240327, 2024. ilus
Artigo em Inglês | LILACS, BBO - Odontologia | ID: biblio-1553444

RESUMO

Aim: Venous blood derivatives (VBDs) have been suggested as substitutes for Fetal Bovine Serum (FBS) to improve the clinical transition of cell-based therapies. The literature is not clear about which is the best VBDs substitute. The present study aimed to evaluate the influence of VBDs on cell viability and describe a new method to seed these cells in a 3D Platelet-Rich Fibrin (PRF). Methods: Blood was processed to obtain Platelet-Poor Plasma from PRF (P-PRF), Human Serum (HS), Platelet-Poor Plasma from PRP (P-PRP), activated-PRP (a-PRP), and Platelet lysate (PL). Cells were supplemented with each VBD at 10% and FBS at 10% was the control. Cell viability (fibroblast 3T3/NIH) test was evaluated with MTT assay in two ways: i) cell-seeded and expanded with VBD; ii) cell-seed with FBS and expanded with VBD. To seed the Fibrin construct, cells were suspended in PBS and dropped into the blood sample before performing Choukroun's protocol for PRF. Constructs were cultured for 7 days in VBD supplements and FBS. Histological and Immunohistochemical analysis with vimentin was performed. Cell viability was analyzed by one-way ANOVA. Results: VBD's production time was very heterogeneous. Cells expanded in HS and a-PRP has grown faster. VBD-supplemented culture media provided cell culture highly sensible to trypsin/EDTA 0.25%. Cells seeded and expanded with VBD presented viability comparable to FBS in HS, a-PRP, and P-PRP (p>0.05) and lower in P-PRF and PL groups (p<0.05). The viability of cell seed with FBS and expanded with VBD was similar between P-PRF, a-PRP, PL, and FBS (p>0.05) and lower in HS and P-PRP (p<0.005). PRF-seeded cells showed a positive expression of vimentin and were able to maintain all cells supplemented with VBD. Conclusion: VBD supplements were able to maintain fibroblast cells in 2D and 3D cultures. The new method of the fibrin-cell construct was efficient to insert the cells into the fibrin network


Assuntos
Sangue , Plaquetas , Soroalbumina Bovina , Fibrina , Células , Fibroblastos , Fibrina Rica em Plaquetas
18.
Front Immunol ; 14: 1323670, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38143761

RESUMO

Growth differentiation factor 11 (GDF11) is one of the important factors in the pathophysiological process of animals. It is widely expressed in many tissues and organs of animals, showing its wide biological activity and potential application value. Previous research has demonstrated that GDF11 has a therapeutic effect on various diseases, such as anti-myocardial aging and anti-tumor. This has not only sparked intense interest and enthusiasm among academics but also spurred some for-profit businesses to attempt to develop GDF11 as a medication for regenerative medicine or anti-aging application. Currently, Sotatercept, a GDF11 antibody drug, is in the marketing application stage, and HS-235 and rGDF11 are in the preclinical research stage. Therefore, we believe that figuring out which cells GDF11 acts on and its current problems should be an important issue in the scientific and commercial communities. Only through extensive, comprehensive research and discussion can we better understand the role and potential of GDF11, while avoiding unnecessary risks and misinformation. In this review, we aimed to summarize the role of GDF11 in different cells and its current controversies and challenges, providing an important reference for us to deeply understand the function of GDF11 and formulate more effective treatment strategies in the future.


Assuntos
Células , Fatores de Diferenciação de Crescimento , Humanos , Animais , Fatores de Diferenciação de Crescimento/metabolismo , Fatores de Diferenciação de Crescimento/uso terapêutico , Células/metabolismo , Biomarcadores , Neoplasias/terapia , Cardiomiopatias/terapia , Inflamação/terapia
20.
Science ; 381(6659): 733-734, 2023 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-37590360

RESUMO

A next step for cell atlases should be to chart perturbations in human model systems.


Assuntos
Atlas como Assunto , Técnicas de Cultura de Células em Três Dimensões , Células , Humanos , Células/classificação , Células/citologia , Organoides
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