Breaking News
October 21, 2018 - Report reveals growing impact of cannabis on young people
October 21, 2018 - NSF awards $5 million grant to help scientists magnify societal impact of research
October 21, 2018 - Fertility Rates Down for Each Urbanization Level 2007 to 2017
October 21, 2018 - Genetically engineered 3-D human muscle transplant in a murine model
October 21, 2018 - Moms’ tight work schedules may affect their children’s sleep
October 21, 2018 - AHA: No Direct Link Between Preeclampsia and Cognitive Impairment, Study Finds
October 21, 2018 - Weight loss success linked with active self-control regions of the brain
October 21, 2018 - Scripps researchers successfully test potential new smoking-cessation treatment in rodents
October 21, 2018 - More accurate and less stressful way to measure a baby’s heartbeat
October 21, 2018 - Researchers show better cardiorespiratory fitness leads to longer life
October 21, 2018 - Healthy candies for diabetic patients
October 21, 2018 - Environment impact of microplastics remains unclear
October 21, 2018 - Antibiotics for appendicitis? Surgery often not needed
October 21, 2018 - AHA and AMA recognize more than 800 medical practices, health systems for blood pressure control
October 21, 2018 - Scientists obtain clearest ever image of Ebola virus protein
October 21, 2018 - Study reveals connection between two proteins known to be hyperactive in cancer
October 21, 2018 - Gabapentin Beats Pregabalin for Chronic Sciatica
October 21, 2018 - Cosmetic surgeons offering incomplete information for breast augmentation customers
October 21, 2018 - Chronic sleep disruption in early adult life accelerates AD-related tau pathology
October 21, 2018 - Take 10 for Mindfulness – Drugs.com MedNews
October 21, 2018 - Length of breathing disruption in OSA may be better predictor of mortality risk
October 21, 2018 - ApoE4 gene linked with chronic inflammation increases risk for Alzheimer’s disease
October 21, 2018 - Mother-daughter conflict associated with suicide risk in abused adolescent girls
October 21, 2018 - Scientists molding bacteria into unnatural shapes
October 21, 2018 - High diet quality associated with lower risk of death in colorectal cancer patients
October 21, 2018 - Discharged mental health patients ‘at greater risk of dying’
October 21, 2018 - Research provides insight into neurobiology of aggression and bullying
October 21, 2018 - As billions in tax dollars flow to private Medicaid plans, Who’s minding the store?
October 21, 2018 - Neuroscientists identify brain region that appears to be related to food preference decisions
October 21, 2018 - Deaths related to air pollution in the U.S. decreased by 47% between 1990 and 2010
October 21, 2018 - Study shows correlation between spatial memory and the sense of smell
October 21, 2018 - Increased cardiorespiratory fitness associated with reduced long-term mortality
October 21, 2018 - IU researchers receive $1.55 million from NIH to improve chronic-disease management
October 21, 2018 - Income and wealth affect the mental health of Australians, study shows
October 21, 2018 - Patients with hypertension and psoriasis more often require cardiovascular interventions
October 20, 2018 - Leading hip-hop videos depict use of tobacco and marijuana products, study finds
October 20, 2018 - Dose Range of IV Ketamine for Adjunct Tx of Depression Tested
October 20, 2018 - Infants can distinguish between leaders and bullies, study finds
October 20, 2018 - Mad Cow disease found on Aberdeenshire farm
October 20, 2018 - Study identifies factors associated with prescription opioid misuse among students
October 20, 2018 - Scientists uncover key regulator of mTORC1 in cancer growth
October 20, 2018 - Pounds Regained After Weight-Loss Op Can Tell Your Doc a Lot
October 20, 2018 - Sending parents letters to fight childhood obesity doesn’t work
October 20, 2018 - Supervised aerobic exercise can support major depression treatment
October 20, 2018 - Mindfulness-based program effective for reducing stress in infertile women
October 20, 2018 - Molecule capable of halting and reverting neurodegeneration caused by Parkinson’s disease identified
October 20, 2018 - Midazolam-mediated alterations of PER2 expression may have functional consequences during myocardial ischemia
October 20, 2018 - Sweat bees are ideal for studying the genes underlying social behavior
October 20, 2018 - Weight loss success associated with brain areas involved in self-control
October 20, 2018 - KHN’s ‘What the Health?’ Republicans’ preexisting political problem
October 20, 2018 - Research provides a more complete picture of suffering caused by terrorist attacks
October 20, 2018 - Eradicating Helicobacter pylori infections may be a key treatment for Parkinson’s disease
October 20, 2018 - Breast Cancer as a Dynamic Disease
October 20, 2018 - University of Pittsburgh wins NSF grant for big data research to prevent complications from anesthesia
October 20, 2018 - Skin-to-skin contact may promote attachment between parents and preterm infants
October 20, 2018 - Recommendations Developed to Verify NGT Placement in Children
October 20, 2018 - Weight loss can be boosted fivefold thanks to novel mental imagery technique
October 20, 2018 - Children with autism are more likely to be overweight, obese
October 20, 2018 - Nurses making conscientious objections to ethically-relevant policies lack support
October 20, 2018 - Prion strain diversity may be greater than previously thought
October 20, 2018 - Antidepressant treatment may lead to improvements in sleep quality of patients with depression
October 20, 2018 - Study reports increased risk of death in children with inflammatory bowel disease
October 20, 2018 - Number of Autism Genes Now Tops 100
October 20, 2018 - Total diet replacement programmes are effective for treating obesity
October 20, 2018 - CLARIOstar used for fluorescence measurements on CSIRO’s purpose-built research vessel
October 20, 2018 - People with more copies of AMY1 gene digest starchy carbohydrates faster
October 20, 2018 - Case Comprehensive Cancer Center wins NIH grant to study health disparities
October 20, 2018 - Newly discovered compound shows potential for treating Parkinson’s disease
October 20, 2018 - High rate of non-adherence to hormonal therapy found among premenopausal early breast cancer patients
October 20, 2018 - Immunotherapy medicine found to be effective in treating uveitis
October 20, 2018 - The Pistoia Alliance Calls for Greater Collaboration to Realise Benefits of Innovation and Announces Winners of the 2018 President’s Startup Challenge
October 20, 2018 - Female internists consistently earn less than men
October 20, 2018 - Stanford team looks at dangers of teens’ vaping habits
October 20, 2018 - New approach to understanding cancers will accelerate development of better treatments
October 20, 2018 - LJI and UC San Diego awarded $ 4.5 million as part of NCI’s Cancer Moonshot initiative
October 20, 2018 - School-based HPV vaccination did not increase risky sexual behaviors among adolescent girls
October 20, 2018 - Eye discovery to pave way for more successful corneal transplants
October 20, 2018 - New analysis examines the importance of location in the opioid crisis
October 20, 2018 - Green filters increase reading speed for children with dyslexia
October 19, 2018 - Bariatric Sx Cuts Macrovascular Complications in Obesity, T2DM
Researchers produce the first draft cell atlas of the small intestine

Researchers produce the first draft cell atlas of the small intestine

image_pdfDownload PDFimage_print
Researchers have produced a first-draft atlas of the mammalian small intestine’s cellular composition. Credit: Grace Burgin, Noga Rogel, and Moshe Biton

The lining or epithelium of the gut is one of the body’s most diverse and dynamic tissues, an ecosystem of cells that acts as one of the body’s main interfaces with the outside world. To better understand this complex tissues and its functions—and the diseases that affect it—a multicenter team led by researchers at the Broad Institute of MIT and Harvard and Massachusetts General Hospital has produced a high-resolution, gene expression-based census of the cells constituting the lining of the small intestine, using more than 53,000 individual cells from the mouse gut or gut organoid models.

This census, published in Nature, comprises a first-draft atlas of the small intestine’s cellular composition, providing a reference for studying the biology of a host of conditions affecting or involving the gut, such as inflammatory bowel disease, cancers of the small intestine, celiac disease, and food allergies. The study also enhances our understanding of the hormones and other signals gut cells produce and sheds new light on how the gut responds to different pathogenic invasions.

The gut has to perform many functions, including absorbing nutrients, generating many of the body’s hormones, and denying entry to noxious substances and pathogens. To do so, it relies on many specialized cells and their specific activities and interactions. Some of these cells are well known, but some have thus far remained unfamiliar.

To carry out their census, the study team relied heavily on single-cell RNA sequencing (scRNA-seq), a suite of genomic techniques capable of identifying specific gene expression profiles within individual cells.

“Every new technology is an opportunity for studying cells and tissues in greater detail,” said Broad core institute member Aviv Regev, a co-corresponding author on the paper, director of the Klarman Cell Observatory (KCO) at the Broad and the institute’s Cell Circuits Program. “They allow us to ask new biological questions or take a fresh look at old ones.

“We wanted to utilize single-cell RNA sequencing to understand what normal intestinal tissue looks like at a deeper level,” she continued. “With that baseline we can start looking at disease.”

“The gut epithelium is in contact with both the immune system and the gut microbiome, and as such the gut is a major hub of cellular connections and therefore it is very important for us to understand gut physiology in health and disease,” said Moshe Biton, a postdoctoral researcher in the KCO and co-first author—with postdoctoral associate Adam Haber and research associate Nogal Rogel—and co-corresponding author on the Nature paper. “It’s also a tissue that we know a great deal about already. So we decided to revisit it and see whether we can find new things using scRNA-seq.”

Leveraging these technologies, the team generated expression profiles for a total of 53,193 small intestinal epithelial cells. Within the data, the team pinpointed expression signatures specific to known cell types (e.g., enterocytes, goblet cells, Paneth cells, tuft cells), specific cell subtypes or populations (e.g., enterocytes at different stages of maturation), and rare cell types (e.g., M cells).

“An exciting outcome of this study was the allocation of known and novel specific sensory molecules associated with each epithelial cell type,” said Rogel. “We hope this will have positive implications in designing drugs targeting metabolic disorders.”

The data also revealed the existence of previously unrecognized cell subtypes and provided support for reclassifying known ones. For instance, the team uncovered a new type of chemical-sensing tuft cell (which helps alert the immune system to infection or other forms of injury) that displayed markers previously thought to be exclusive to immune cells and which may help sound the alarm about allergens and invading parasites.

“We were surprised to see that expression of the gene TSLP—which encodes a cytokine long known to be involved in epithelial-induced inflammation—was exclusive to a particular subset of tuft cells,” Haber noted. “This suggests a significant ‘lookout’ role for these recently characterized cells.”

In addition, the data showed that the gut’s hormone-producing enteroendocrine cells (EECs)—long divided into subsets based on the idea that each only expressed a single hormone—can actually express multiple hormones at once.

The team also mapped their data to different locations along the length of the small intestinal tract. For example, they found that EECs that produce ghrelin (which triggers hunger) tend to group near the beginning of the small intestine (the duodenum, adjacent to the stomach). Those producing peptide YY (which prompts the feeling of being sated), on the other hand, aggregate near the far end (the ileum).

As a proof-of-concept of the atlas’s utility as a reference for disease studies, the researchers also surveyed gut epithelial gene expression in two models of intestinal infection, one of Salmonella bacteria, the other of Heligmosomoides polygyrus, a species of helminth (an intestinal parasite).

Comparisons against the reference census data showed that the intestinal lining dramatically reconfigures itself in response to infection. Certain cell types significantly increased or declined in abundance depending on the kind of infectious insult. Many cells’ expression profiles also changed dramatically, including pathogen-specific changes.

With the reference cell census data in hand, the research team is excited to conduct additional studies, including ones involving models or human patients with gastrointestinal conditions—Crohn’s disease, ulcerative colitis, gastrointestinal cancers, forms of food allergy, to name a few—aimed at identifying changes in gene expression and epithelial structure and function that could reveal new insights and opportunities for therapeutic development.

“We see this atlas providing a foundation for investigating many different questions about the pathology in the gut, effects of drug-induced gut toxicities and for identifying and examining important cells, interactions, and biomarkers,” said Broad institute member Ramnik Xavier, a co-corresponding author on the paper, co-director of the institute’s Infectious Disease and Microbiome Program, and chief of gastroenterology and director of the Center for the Study of Inflammatory Bowel Disease at MGH. “And in creating this resource, we have learned a great deal about how to build an atlas of a complex, dynamic tissue. That kind of knowledge could be important for other efforts focused on other tissues and systems.”


Explore further:
Immune cells produce wound healing factor, could lead to new IBD treatment

More information:
Adam L. Haber et al. A single-cell survey of the small intestinal epithelium, Nature (2017). DOI: 10.1038/nature24489

Journal reference:
Nature

Provided by:
Broad Institute of MIT and Harvard

Tagged with:

About author

Related Articles