The Atlas of Human Developmental Cells Reveals the "Black Box" of Embryonic Development

Diagram of human embryonic development
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Construction of the human developmental cell map
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A year ago, the world's first human cell atlas was successfully drawn at Zhejiang University
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As an important strategy of the Human Cell Atlas (HCA) project, the Human Developmental Cell Atlas (HDCA) project aims to construct a fine reference map of the spatiotemporal expression of cell genes in the process of complete human development (from the fertilized egg to the fully formed fetus at birth) , To establish a holographic human embryonic development information network
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Plan to uncover the "black box" of human embryonic development

Guo Guoji, one of the authors of the paper, told the China Science News, “The Human Cell Atlas Project will generate larger life science data than the Human Genome Project, and it will also face more technical challenges than the Human Genome Project
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"Through the joint efforts of scientists around the world and the comparative analysis of data from multiple regions and multiple laboratories, we will eventually achieve the grand goal of high-precision human cell atlases
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At present, the research of modern developmental biology is mostly focused on model organisms.
Due to practical challenges, human embryonic development is still a poorly understood "black box"
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Many congenital diseases and childhood cancers originate from susceptible developmental windows; in addition, the development trajectory of human embryos can also provide important reference and guidance for human stem cell models, organoids and cell therapy
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The early studies of human development started with the morphological measurement and qualitative evaluation of embryos, and based on this, the Carnegie phylogeny was constructed
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The use of these latest technologies to construct a comprehensive reference map of human development at a single-cell resolution is an ambitious project.
Its scale is similar to the "Human Genome Project".
It requires laboratories from all over the world and large national and international research alliances.
Participation also requires the collaboration of multidisciplinary scientific expertise in different fields
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Guo Guoji said that, like the Human Cell Atlas (HCA) project, the Human Developmental Cell Atlas website will be composed of multiple data types such as genome, transcriptome, and proteome to realize the visualization of cells expressed in the space and time of human embryonic development and provide free sharing for scientists around the world.
Database of basic science resources
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Construction of Human Developmental Cell Atlas

The Human Developmental Cell Atlas project poses huge scientific challenges to experimental technology, computational analysis and visualization algorithms, especially the capture of transient embryonic morphological changes in the first eight weeks of pregnancy
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In addition, the Human Developmental Cell Atlas will adopt the funding, implementation, coordination and sharing methods of large-scale scientific projects initiated by the Human Genome Project, as well as the ethics committee and "biological network" based on the Human Cell Atlas (HCA)
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This organizational framework enables researchers to form large-scale coordinated collaborations across technical and biological disciplines: including developmental biology, embryology, genetics and model systems, computational biology, clinical specialties (including in vitro fertilization), clinical genetics, and Pathology
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The entire process of human embryo development is regulated by three-dimensional space and time
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Human embryogenesis cannot be easily assessed with high resolution in vivo, and time-series research is limited to preimplantation embryos in vitro.
These problems will be the challenge for us to successfully construct a human developmental cell map
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The application of high-throughput genomics technology to separate cells and tissue sections in situ has begun to provide unprecedented high-resolution data for developmental biology
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Single-cell molecular maps based on RNA, chromatin accessibility, methylation, or specific proteins make the definition of cell types and states more nuanced
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The definition of cell types currently mainly refers to the atlas of model organisms and adult cells, but these analyses are not necessarily applicable to transient cell types that exist during the transitional state of development and differentiation
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"In order to overcome these challenges, many time points need to be analyzed, and the defined cell state needs to be mapped back to its three-dimensional space and functionally characterized over time
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" Guo Guoji said that for the complete human developmental cell atlas (HDCA), Gao The level of multi-omics technology can reflect the multi-faceted state of cell molecular profile, morphological function and other characteristics
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For example, the transcriptome reflects the present and potential future of the cell; protein expression captures the past and present of the cell; the chromatin profile reveals its unchanging type and future differentiation potential; individual lineage development reveals its history
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We look forward to the development of developmental biology towards a consistent cell ontology, integrating spatial transcriptome, single-cell sequencing, in-situ sequencing and other multi-omics single-cell analysis methods, drawing a comprehensive three-dimensional developmental cell map, and restoring real human embryonic development molecules.
Process
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Clinical application of human developmental cell atlas

The interaction between genotype and environment is the basis for the early developmental obstacles in humans
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A series of childhood and adult diseases originated in the embryonic period, including structural birth defects, neurodevelopmental disorders (including schizophrenia), childhood cancer, congenital immune deficiency, infertility and gender development differences, and many pediatric diseases
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"Many rare genetic diseases will have a series of sequelae of dysplasia at birth, and sometimes even if they are classified as the same disease or disease, their medical manifestations are very different
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" Guo Guoji said
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For example, Down syndrome (trisomy 21) and 22q11.
2 deletion syndrome have major risks of schizophrenia, Alzheimer's disease, and hypothyroidism starting from puberty, respectively
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Due to our limited understanding of normal human development, it is impossible to determine the cause of developmental disorders and the influence of maternal genotype, paternal age, and other external risk factors (such as diet, alcohol, toxins, endocrine disruptors, and pathogens)
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The construction of the Human Developmental Cell Atlas (HDCA) can reveal the pathogenesis of childhood cancer
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Brain tumors in children and adults often have procedural abnormalities in the early stages of development
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Comparing the expression profile of tumor cells with the Human Developmental Cell Atlas (HDCA) can determine the origin of cancer cells and their carcinogenic pathways
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For example, the single-cell atlas of the developing mouse cerebellum has been used to study the subtypes of human medulloblastoma, and the cell status in the process of nephrogenesis reveals the developmental cell origin of Wilms tumor
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The high-resolution atlas of developing immune cells will provide a reference for the molecular basis and development of the disease phenotypes of childhood leukemia and primary immunodeficiency
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Many adult cancers are also caused by dysregulation of human early developmental programs
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Human Developmental Cell Atlas (HDCA) data can also be used to detect the expression of virus entry receptors and proteases in various organs, helping us understand the different susceptibility to SARS-CoV-2 during adult and embryonic periods
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Cell and tissue engineering for clinical treatment and regenerative medicine is a promising application field of the Human Developmental Cell Atlas (HDCA)
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Cell therapy derived from human pluripotent stem cells is entering early clinical trials for the treatment of Parkinson's disease.
The protocol used is to study the differentiation of midbrain dopaminergic neurons based on developmental improvements
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Similar methods have spawned a series of other stem cell products for human trials.
For example, hematopoietic stem cell transplantation is a widely used treatment method for many blood diseases.
Using the hematopoietic potential of embryonic hematopoietic stem cells can bring substantial benefits to patients with blood diseases
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(Source: China Science News, Cui Xueqin)

Related paper information: https://doi.
org/10.
1038/s41586-021-03620-1