How are organs and tissues organized at the cellular level? The first detailed, single cell-resolution spatial maps of human organs and tissues have recently been published as part of the HuBMAP Consortium’s work. These molecular maps of human organs provide an unprecedented level of insight into the connections between the structural and genetic features of these tissues, providing much better cell type context.
The HuBMAP Consortium
Established in 2019, the NIH’s Human Biomolecular Atlas Program (HuBMAP) Consortium focuses on generating spatially resolved single-cell maps of major organs and tissue types in healthy and diseased states. By combining diverse institutional expertise, HuBMAP aims to create a comprehensive and accessible 3-D molecular atlas of the human body.
This project is made possible by the advent of sophisticated single cell sequencing and imaging tools. One of the most popular sequencing-based spatial methods is single cell transcriptomics. Slices of tissue are placed on a specialized slide coated in molecular barcodes that encode their positional information and bind to the RNA in the tissue. When the RNA including the barcode is sequenced, its original location on the slide and in the tissue can be identified. Imaging-based methods use antibodies against a panel of proteins tagged with either heavy metal isotopes or DNA barcodes that can be detected using mass spectrometry and fluorescence microscopy, respectively.
Unraveling Tissue Complexity at Single-Cell Resolution
Three papers from the consortium were recently published in Nature, detailing molecular maps of the (1) human intestine, (2) kidney, and (3) placenta.
In the human intestine study, the authors used barcode-based imaging, single nucleus RNA sequencing and open chromatin assays to investigate eight different regions of the intestine. They discovered new subtypes of epithelial cells arranged in distinct “neighborhoods,” an insight made possible by the use of spatial techniques. They also uncovered new immunological niches, which could be important for understanding diseases of inflammation of the intestine.
To characterize the human kidney, researchers studied 45 healthy and 48 diseased kidneys. Spatial analysis revealed cell-cell communication between cells with poor tissue repair ability and other scarring and inflammation-related cells. Their findings point to potential avenues for better understanding normal kidney function and kidney failure.
The third paper examined the human placenta, specifically, the interface between the fetal placenta and maternal uterine wall. Remodeling of maternal arteries takes place to deliver blood to areas where maternal and fetal cells interact, and the authors’ maps showed how an immune-tolerant environment is created around the arteries to allow genetically distinct maternal and fetal cells to coexist.
Cell-Level Reference Maps: Looking Forward
Studying tissues at the single cell level with spatial resolution is a computational task as much as an experimental one. As these tissue maps become even more granular, incorporating subcellular positioning data, the collaboration between bioinformaticians and bench biologists will be even more important to draw new insights.
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Jane Cook, Biochemist & Content Writer, Bridge Informatics
Jane Cook, the leading Content Writer for Bridge Informatics, has written over 100 articles on the latest topics and trends for the bioinformatics community. Jane’s broad and deep interdisciplinary molecular biology experience spans developing biochemistry assays to genomics. Prior to joining Bridge, Jane held research assistant roles in biochemistry research labs across a variety of therapeutic areas. While obtaining her B.A. in Biochemistry from Trinity College in Dublin, Ireland, Jane also studied journalism at New York University’s Arthur L. Carter Journalism Institute. As a native Texan, she embraces any challenge that comes her way. Jane hails from Dallas but returns to Ireland any and every chance she gets. If you’re interested in reaching out, please email [email protected] or [email protected].