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Human Cell Atlas of Fetal Gene Expression



Genomics of Human Development

Understanding the trajectory of a developing human requires understanding how to regulate and express genes. Two papers now propose a pooling method that uses three levels of combinatorial indexing to examine single-cell gene expression and chromatin distribution in 15 organs in fetal samples. o Wait. Focus on the measurement of RNA in a wide range of cell types and gain insight into organ specificity.Domke Wait. The chromatin accessibility of cells in these organs was examined and the regulatory elements that regulate gene expression were determined. These analyses together produced a comprehensive atlas of early human development.

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Structured abstract

Introduction

The reference map of human cell types is the main goal in this field.Here, we set out to generate single-cell maps of gene expression (this study) and chromatin accessibility (Domcke) Wait.(This question) Use a variety of human tissues obtained during pregnancy.

Justification

Contemporary knowledge about the molecular basis of human development in vivo mainly comes from human genetics, in vivo studies of model organisms, and in vitro studies of differentiated human cell lines, rather than through direct studies of developing human tissues. Historically, several challenges have limited the development of human tissue research at the molecular level, including limited access, tissue degradation, and cell type heterogeneity. For this and accompanying research (Domcke Wait., This problem), we can overcome these challenges.

result

We applied a three-level single-cell combinatorial index for gene expression (sci-RNA-seq3) to 121 human fetal samples (ranging from 72 days to 129 days) after concept expression. They represent 15 organs and analyzed in total 4 million single cells. We developed and applied a framework for quantifying cell type specificity and identifying 657 cell subtypes, and we made preliminary annotations based on cross-matching with mouse cell maps. We have identified and validated potentially circulating trophoblast-like and hepatoblast-like cells in unexpected tissues. Gene expression analysis in different tissues facilitates cross-tissue analysis of a wide range of cell types (including blood, endothelial cells, and epithelial cells). For blood cells, this produces a multi-organ map of cell state trajectories from hematopoietic stem cells to all major sublines. Various evidence supports that during fetal development, the adrenal gland is a normal (albeit a minor) site of red blood cell production. Although the species and developmental stage are different, it is obviously very simple to integrate these human fetal data with the mouse embryonic cell atlas. For some systems, this essentially allows us to transition gene expression kinetics from the embryonic stage of mammalian development to the fetal stage.

in conclusion

The single-cell data resources introduced in this article are known for their scale, focus on human fetal development, the breadth of tissue analyzed, and the parallel generation of gene expression (this study) and chromatin accessibility data (Domcke). Wait., this problem). We have further consolidated the technical framework of each laboratory to generate and analyze gene expression and chromatin accessibility data from millions of single cells. Looking to the future, we expect that the mid-term human development window studied here will be slightly narrower, which will be supplemented by other atlases at early and late time points, and similar comprehensive analysis and integration of data from model organisms. The continuous development and application of methods for determining gene expression and chromatin accessibility (combined with spatial, epigenetics, proteomics, lineage history, and other information) is a starting point for a comprehensive understanding of the diversity of human cell types Development is essential. In a single cell zygote. An interactive website can facilitate the exploration of these free data by tissue, cell type or gene (descartes.brotmanbaty.org).

The human cell profile of fetal gene expression enables the exploration of in vivo gene expression in multiple cell types.

We use three-level combinatorial index analysis (sci-RNA-seq3) to analyze gene expression in approximately 4,000,000 single cells from 15 fetal organs. This abundant resource can realize, for example, the identification and annotation of cell types, the cross-tissue integration of widely distributed cell types (such as blood, endothelial cells and epithelial cells), and the interspecies integration of mouse embryo and human fetal cell maps. PCR, polymerase chain reaction.

abstract

It is of fundamental significance to standardize the gene expression program of human cell types. We generated a human cell profile of gene expression and chromatin accessibility in fetal tissues. For gene expression, we applied a three-level combinatorial index to more than 110 samples representing 15 organs, and finally analyzed about 4 million single cells. We use literature and other atlases to identify and annotate hundreds of cell types and subtypes within and across tissues. Our analysis focuses on widely distributed cell types (such as blood, endothelial cells, and epithelial cells), organ-specific expertise in fetal red blood cell production sites (especially adrenal glands), and integration with mouse developmental maps (such as conservative specifications for blood) )cell). These data represent a rich resource for exploring human gene expression in multiple tissues and cell types.


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