A roadmap for the Human Developmental Cell Atlas
Wellcome Trust Sanger Institute1, Newcastle University2, Children's Hospital of Philadelphia3, University of Pennsylvania4, Karolinska Institutet5, Cincinnati Children's Hospital Medical Center6, University of Toronto7, University of Cambridge8, University of Basel9, Vision Institute10, UCL Institute of Child Health11, Aix-Marseille University12, university of lille13, Zhejiang University14, Broad Institute15, McGill University16, University of California, San Francisco17, Royal Institute of Technology18, Francis Crick Institute19, Science for Life Laboratory20, Memorial Sloan Kettering Cancer Center21, Genentech22, Massachusetts Institute of Technology23, New York University24, ETH Zurich25
TL;DR: The Human Developmental Cell Atlas (HDCA) project as discussed by the authors aims to create a comprehensive reference map of cells during development by mapping and modelling human development using state-of-the-art technologies.
Abstract: The Human Developmental Cell Atlas (HDCA) initiative, which is part of the Human Cell Atlas, aims to create a comprehensive reference map of cells during development. This will be critical to understanding normal organogenesis, the effect of mutations, environmental factors and infectious agents on human development, congenital and childhood disorders, and the cellular basis of ageing, cancer and regenerative medicine. Here we outline the HDCA initiative and the challenges of mapping and modelling human development using state-of-the-art technologies to create a reference atlas across gestation. Similar to the Human Genome Project, the HDCA will integrate the output from a growing community of scientists who are mapping human development into a unified atlas. We describe the early milestones that have been achieved and the use of human stem-cell-derived cultures, organoids and animal models to inform the HDCA, especially for prenatal tissues that are hard to acquire. Finally, we provide a roadmap towards a complete atlas of human development. This Perspective outlines the Human Developmental Cell Atlas initiative, which uses state-of-the-art technologies to map and model human development across gestation, and discusses the early milestones that have been achieved.
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Wellcome Trust Sanger Institute1, Laboratory of Molecular Biology2, Queen Mary University of London3, University of Cambridge4, Newcastle University5, University College London6, Cambridge University Hospitals NHS Foundation Trust7, European Bioinformatics Institute8, John Radcliffe Hospital9, University of Oxford10, Garvan Institute of Medical Research11
TL;DR: The cellular landscape of the human intestinal tract is dynamic throughout life, developing in utero and changing in response to functional requirements and environmental exposures as discussed by the authors, using single-cell RNA sequencing and antigen receptor analysis of almost half a million cells from up to 5 anatomical regions of the developing and up to 11 distinct anatomical regions in the healthy human gut.
Abstract: The cellular landscape of the human intestinal tract is dynamic throughout life, developing in utero and changing in response to functional requirements and environmental exposures. Here, to comprehensively map cell lineages, we use single-cell RNA sequencing and antigen receptor analysis of almost half a million cells from up to 5 anatomical regions in the developing and up to 11 distinct anatomical regions in the healthy paediatric and adult human gut. This reveals the existence of transcriptionally distinct BEST4 epithelial cells throughout the human intestinal tract. Furthermore, we implicate IgG sensing as a function of intestinal tuft cells. We describe neural cell populations in the developing enteric nervous system, and predict cell-type-specific expression of genes associated with Hirschsprung’s disease. Finally, using a systems approach, we identify key cell players that drive the formation of secondary lymphoid tissue in early human development. We show that these programs are adopted in inflammatory bowel disease to recruit and retain immune cells at the site of inflammation. This catalogue of intestinal cells will provide new insights into cellular programs in development, homeostasis and disease. Cells from embryonic, fetal, paediatric and adult human intestinal tissue are analysed at different locations along the intestinal tract to construct a single-cell atlas of the developing and adult human intestinal tract, encompassing all cell lineages.
163 citations
TL;DR: An overview of the basic principles of cell types rooted in evolution and development and approaches to characterize and classify cell types and investigate how they contribute to the organism's function, using the mammalian brain as a primary example as mentioned in this paper .
73 citations
TL;DR: Rossant and Tam as mentioned in this paper discuss new insights into human embryogenesis gathered from successes in culturing human embryos in vitro and stem-cell-based embryo models, and outline what questions still need answering.
35 citations
TL;DR: ConsensusPathDB (http://consensuspathdb.org) is a meta-database combining interactions of diverse types from 31 public resources for humans, 16 for mice and 14 for yeasts as discussed by the authors.
Abstract: Molecular interactions are key drivers of biological function. Providing interaction resources to the research community is important since they allow functional interpretation and network-based analysis of molecular data. ConsensusPathDB (http://consensuspathdb.org) is a meta-database combining interactions of diverse types from 31 public resources for humans, 16 for mice and 14 for yeasts. Using ConsensusPathDB, researchers commonly evaluate lists of genes, proteins and metabolites against sets of molecular interactions defined by pathways, Gene Ontology and network neighborhoods and retrieve complex molecular neighborhoods formed by heterogeneous interaction types. Furthermore, the integrated protein-protein interaction network is used as a basis for propagation methods. Here, we present the 2022 update of ConsensusPathDB, highlighting content growth, additional functionality and improved database stability. For example, the number of human molecular interactions increased to 859 848 connecting 200 499 unique physical entities such as genes/proteins, metabolites and drugs. Furthermore, we integrated regulatory datasets in the form of transcription factor-, microRNA- and enhancer-gene target interactions, thus providing novel functionality in the context of overrepresentation and enrichment analyses. We specifically emphasize the use of the integrated protein-protein interaction network as a scaffold for network inferences, present topological characteristics of the network and discuss strengths and shortcomings of such approaches.
17 citations
TL;DR: In this article , a detailed protocol for generating hair-bearing skin tissue entirely from a homogeneous population of human pluripotent stem cells in a three-dimensional in vitro culture system is described.
Abstract: Human skin uses millions of hairs and glands distributed across the body surface to function as an external barrier, thermoregulator and stimuli sensor. The large-scale generation of human skin with these appendages would be beneficial, but is challenging. Here, we describe a detailed protocol for generating hair-bearing skin tissue entirely from a homogeneous population of human pluripotent stem cells in a three-dimensional in vitro culture system. Defined culture conditions are used over a 2-week period to induce differentiation of pluripotent stem cells to surface ectoderm and cranial neural crest cells, which give rise to the epidermis and dermis, respectively, in each organoid unit. After 60 d of incubation, the skin organoids produce hair follicles. By day ~130, the skin organoids reach full complexity and contain stratified skin layers, pigmented hair follicles, sebaceous glands, Merkel cells and sensory neurons, recapitulating the cell composition and architecture of fetal skin tissue at week 18 of gestation. Skin organoids can be maintained in culture using this protocol for up to 150 d, enabling the organoids to be used to investigate basic skin biology, model disease and, further, reconstruct or regenerate skin tissue.
13 citations
References
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Technical University of Madrid1, Stanford University2, Elsevier3, VU University Amsterdam4, National Institutes of Health5, University of Leicester6, Harvard University7, Beijing Genomics Institute8, Maastricht University9, Wageningen University and Research Centre10, University of Oxford11, Heriot-Watt University12, University of Manchester13, University of California, San Diego14, Leiden University Medical Center15, Leiden University16, Federal University of São Paulo17, Science for Life Laboratory18, Bayer19, Swiss Institute of Bioinformatics20, Cray21, University Medical Center Groningen22, Erasmus University Rotterdam23
TL;DR: The FAIR Data Principles as mentioned in this paper are a set of data reuse principles that focus on enhancing the ability of machines to automatically find and use the data, in addition to supporting its reuse by individuals.
Abstract: There is an urgent need to improve the infrastructure supporting the reuse of scholarly data. A diverse set of stakeholders—representing academia, industry, funding agencies, and scholarly publishers—have come together to design and jointly endorse a concise and measureable set of principles that we refer to as the FAIR Data Principles. The intent is that these may act as a guideline for those wishing to enhance the reusability of their data holdings. Distinct from peer initiatives that focus on the human scholar, the FAIR Principles put specific emphasis on enhancing the ability of machines to automatically find and use the data, in addition to supporting its reuse by individuals. This Comment is the first formal publication of the FAIR Principles, and includes the rationale behind them, and some exemplar implementations in the community.
7,602 citations
01 May 2017
TL;DR: ROZA was developed under the umbrella of LTER-France (Long Term Ecological Research) in order to facilitate the re-use of data and samples and will favor to use of paleodata by non-paleodata scientists, in particular ecologists.
Abstract: Managing paleoscience data is highly challenging to the multiplicity of actors in play, types of sampling, analysis, post-analysis treatments, statistics etc. However, a well-structured curating of data would permit innovative developments based on data and/or sample re-use, such as meta-analysis or the development of new proxies on previously studied cores. In this paper, we will present two recent initiatives that allowed us tackling this objective at a French national level: the “National Cyber Core Repository” (NCCR) and the “LTER-France retro-observatory” (ROZA).NCCR was developed under the umbrella of the French National Center fo Coring and Drilling (C2FN) thanks to the national excellence equipment project CLIMCOR. It aims at gathering on a unique website the locations and metadata of any scientific coring/drilling performed by French teams or using French facilities, whatever the type of archive it is (lake/marine sediment; ice etc.). It uses international standard, notably IGSN (for samples), ORCID (for persons) and DOI (for campaigns). NCC follows the INSPIRE ISO 19115 standard in order to catalogue the data. For continental sediment, NCCR may be fed directly on the field through a specifically developed mobile application.Based on NCCR, further initiatives may be led. In particular, under the umbrella of LTER-France (Long Term Ecological Research), we developed ROZA in order to facilitate the re-use of data and samples. Here the idea is to capitalise the knowledge on a given lake from which several sediment cores can be taken through time. In that aim we selected at least one lake from each of the 13 areas composing the network LTER-France. To enter the database, a set of mandatory data must be provided under a pre-determined format. In that case, the insertion of ROZA within the network LTER will favor to use of paleodata by non-paleodata scientists, in particular ecologists.
3,648 citations
TL;DR: A human pluripotent stem cell-derived three-dimensional organoid culture system that develops various discrete, although interdependent, brain regions that include a cerebral cortex containing progenitor populations that organize and produce mature cortical neuron subtypes is developed.
Abstract: The complexity of the human brain has made it difficult to study many brain disorders in model organisms, highlighting the need for an in vitro model of human brain development Here we have developed a human pluripotent stem cell-derived three-dimensional organoid culture system, termed cerebral organoids, that develop various discrete, although interdependent, brain regions These include a cerebral cortex containing progenitor populations that organize and produce mature cortical neuron subtypes Furthermore, cerebral organoids are shown to recapitulate features of human cortical development, namely characteristic progenitor zone organization with abundant outer radial glial stem cells Finally, we use RNA interference and patient-specific induced pluripotent stem cells to model microcephaly, a disorder that has been difficult to recapitulate in mice We demonstrate premature neuronal differentiation in patient organoids, a defect that could help to explain the disease phenotype Together, these data show that three-dimensional organoids can recapitulate development and disease even in this most complex human tissue
3,508 citations
TL;DR: Previously undescribed prognostic subclasses of high-grade astrocytoma are identified and discovered to resemble stages in neurogenesis, suggesting functional relevance of tumor subtype molecular signatures is suggested by the ability of cell line signatures to predict neurosphere growth.
2,840 citations
TL;DR: In this paper, the expression of viral entry-associated genes in single-cell RNA-sequencing data from multiple tissues from healthy human donors was investigated, and co-detected these transcripts in specific respiratory, corneal and intestinal epithelial cells, potentially explaining the high efficiency of SARS-CoV-2 transmission.
Abstract: We investigated SARS-CoV-2 potential tropism by surveying expression of viral entry-associated genes in single-cell RNA-sequencing data from multiple tissues from healthy human donors. We co-detected these transcripts in specific respiratory, corneal and intestinal epithelial cells, potentially explaining the high efficiency of SARS-CoV-2 transmission. These genes are co-expressed in nasal epithelial cells with genes involved in innate immunity, highlighting the cells' potential role in initial viral infection, spread and clearance. The study offers a useful resource for further lines of inquiry with valuable clinical samples from COVID-19 patients and we provide our data in a comprehensive, open and user-friendly fashion at www.covid19cellatlas.org.
2,024 citations