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Science Papers Present Approach to Assess Gut Microbe Gene Expression; Single-Cell Transcriptomic Atlas; More

A noninvasive system for assessing gut function was reported in Science last week. Bacteria within the gut continuously adapt their gene expression to environmental conditions that are associated with diet, health, and disease. However, current methods for examining in vivo microbiota physiology and pathophysiology are unable to provide detailed information about transient or proximal events within the intestine without disturbing normal gut functioning. To overcome this, scientists from ETH Zurich developed Record-seq, an approach that uses the CRISPR spacer adaptation complex of Fusicatenibacter saccharivorans to acquire snippets of cellular RNAs as DNA within CRISPR arrays that can later be sequenced to reveal memory of past microbial gene expression. Record-seq, they write, "captures transcriptome-scale information about the intestinal environment, recording the differences in microbiota-host interactions according to diet, disease, or alterations of microbiota composition." The tool, the researchers add, may aid in exploring intestinal and microbiota physiology under different dietary conditions, disease contexts, or constraints in humans where longitudinal sample collection based on surgical, endoscopic, fecal, ingestible device, or post-mortem methods are not possible.

Meanwhile, members of the international Human Cell Atlas consortium published maps of more than one million individual cells across 33 organs in Science this week, representing the most comprehensive cross-tissue cell atlas available. In the first study, the Tabula Sapiens Consortium reported a human reference atlas comprising nearly 500,000 cells from 24 different tissues and organs, many from the same donor. With the atlas, they molecularly characterized more than 400 cell types, their distribution across tissues, and tissue-specific variation in gene expression. Having multiple tissues from a single donor, meantime, enabled the identification of the clonal distribution of T cells between tissues, the tissue specific mutation rate in B cells, and analysis of the cell cycle state and proliferative potential of shared cell types across tissues

In the second report, a group led by Broad Institute scientists described using four single nucleus RNA-seq methods to analyze frozen samples across eight organs from 16 donors, generating a cross-tissue atlas of 209,126 nuclei profiles. Using machine learning, they associated cells in the atlas with thousands of single-gene diseases and complex genetic diseases and traits to discover cell types and gene programs that could be involved in disease. The work, they write, will "form a basis for larger-scale future studies to improve our understanding of cross-tissue and cross-individual variation of cellular phenotypes in relation to disease-associated genetic variation."

Next, a multi-institute team headed by Wellcome Sanger Institute investigators used single-cell RNA sequencing and VDJ sequencing to survey innate and adaptive immune cells from 16 tissues across 12 adult donors, resulting in gene expression profiles for more than 360,000 cells. They then developed a machine learning tool for cell type annotation that enabled them to determine the tissue distribution of finely phenotyped immune cell types, "revealing hitherto unappreciated tissue-specific features and clonal architecture of T and B cells. Our multi-tissue approach lays the foundation for identifying highly resolved immune cell types by leveraging a common reference dataset, tissue-integrated expression analysis and antigen receptor sequencing," they wrote.

Lastly, another Wellcome Sanger Institute-led team applied scRNA-seq, antigen-receptor sequencing, and spatial transcriptomics to nine prenatal tissues to generate a single-cell and spatial atlas of the developing immune system across gestational stages. The work reveals "the acquisition of immune effector functions of myeloid and lymphoid lineages from the second trimester, the maturation of developing monocytes and T cells prior to peripheral tissue seeding, and system-wide blood and immune cell development during human prenatal development." With the atlas, the scientists also identify, characterize, and functionally validate the properties of human prenatal B1 cells and the origin of unconventional T cells. The resource is expected to facilitate in vitro cell engineering and regenerative medicine, and improve our understanding of congenital disorders affecting the immune system, according to the researchers.

GenomeWeb has more on these Human Cell Atlas studies here.