Breaking News
August 14, 2018 - Rethinking the stroke rule ‘time is brain’
August 14, 2018 - Incidence of coronary artery compression in children may be more common than previously thought
August 14, 2018 - Study helps to better understand disease caused by Alpha-1 antitrypsin deficiency
August 14, 2018 - AI platform identifies acute neurological illnesses faster than human diagnosis
August 14, 2018 - American College of Rheumatology receives grants to support development of lupus clinical trials
August 14, 2018 - American Heart Association Urges Screen Time Limits for Youth
August 14, 2018 - Brief interventions during routine care reduce alcohol use among men with HIV
August 14, 2018 - New genome analysis could identify people at higher risk of common deadly diseases
August 14, 2018 - NIH grant for Mount Sinai to study use of inhaled corticosteroids for treatment of sickle cell disease
August 14, 2018 - Daicel supplies free nanodiamond samples to international researchers
August 14, 2018 - Switching anti-psychotic drugs in first-episode schizophrenia patients does not improve clinical outcomes
August 14, 2018 - Study to examine whether modulating gut bacteria can improve cardiac function in heart failure patients
August 14, 2018 - AI technology could hold key to improving health services
August 14, 2018 - One out of two children not getting enough nutrients needed for their health
August 14, 2018 - Mono-antiplatelet therapy after aortic heart valve replacements may work as well as two drugs
August 14, 2018 - Aid-in-dying patient chooses his last day
August 14, 2018 - Exercise Really Can Chase Away the Blues, to a Point
August 14, 2018 - Surgical mesh implants may cause autoimmune disorders
August 14, 2018 - Researchers develop revolutionary zebrafish model to gain more insight into bone diseases
August 14, 2018 - Researchers discover secret communication hotline between breast cancers and normal cells
August 14, 2018 - Study examines how a person adapts to visual field loss after stroke
August 14, 2018 - Researchers show how specialized nucleic acid-based nanostructures could help target cancer cells
August 14, 2018 - Reducing opioid prescriptions for one operation can also spill over to other procedures
August 14, 2018 - E-cigarettes not so safe but still better than cigarettes
August 14, 2018 - Researchers find link between common ‘harmless’ virus and cardiovascular damage
August 14, 2018 - Initiation of PIMs associated with higher risk of fracture-specific hospitalizations and mortality
August 14, 2018 - Genetically modified mosquitoes and special bed nets help tackle deadly diseases
August 14, 2018 - Advances in treating hep C lead to new option for transplant patients
August 14, 2018 - Study finds quality of doctor-patient discussions about lung cancer screening to be ‘poor’
August 14, 2018 - MSU researchers uncover the effects of aging on regenerative ability of kidneys
August 14, 2018 - Better conditioning, throwing mechanics can help reduce elbow injuries in young baseball pitchers
August 14, 2018 - Brain game doesn’t offer brain gain
August 14, 2018 - Reproductive choices facing women with disabilities require careful consideration
August 14, 2018 - Scientists pinpoint the cause of a rare childhood seizure disorder
August 14, 2018 - Lumpectomy plus radiation associated with reduced risk of breast cancer death, study finds
August 14, 2018 - UAB study shows how ion channel differentiates newborn and mature neurons in the brain
August 14, 2018 - Experts highlight key knowledge gaps that need to be addressed in Ebola vaccine research
August 14, 2018 - Discovery could lead to new drugs against infection and inflammation
August 14, 2018 - Infection Prevention Differs Between Small, Large Hospitals
August 14, 2018 - Mom still matters—In study, young adults tended to prioritize parents over friends
August 14, 2018 - Deep brain stimulation might benefit those with severe alcoholism, preliminary studies show
August 14, 2018 - Study finds increased rate of repeat pregnancies in women with intellectual and developmental disabilities
August 14, 2018 - Lighter sedation fails to reduce risk of postoperative delirium in older patients
August 13, 2018 - Asking better questions about person’s memory could improve doctors’ understanding of patients
August 13, 2018 - U.S. Trauma Doctors Push for Stricter Gun Controls
August 13, 2018 - Asthma and flu: a double whammy
August 13, 2018 - 5 Questions: Donna Zulman on engaging high-need patients in intensive outpatient programs | News Center
August 13, 2018 - Behavioral Nudges Lead to Drop in Prescriptions of Potent Antipsychotic
August 13, 2018 - Potential New Class of Drugs May Reduce Cardiovascular Risk by Targeting Gut Microbes
August 13, 2018 - How to get your kids to eat better
August 13, 2018 - The importance of hearing your patients
August 13, 2018 - Transmission of F. tularensis unlikely to happen through the food chain
August 13, 2018 - Researchers discover epigenetic mechanism underlying ischemic cardiomyopathy
August 13, 2018 - Adolescent health programs receive only a tiny share of international aid, finds research
August 13, 2018 - Fracture risk increases by 30% after gastric bypass, study shows
August 13, 2018 - Quality-improvement project to standardize feeding practices helps micro preemies gain weight
August 13, 2018 - Long-term cannabinoid exposure impairs memory, study shows
August 13, 2018 - New intervention to reduce risk of HIV in young transgender women
August 13, 2018 - Japan human trial tests iPS cell treatment for Parkinson’s
August 13, 2018 - Altered nitrogen metabolism may contribute to emergence of new cancer mutations
August 13, 2018 - Cycling provides greatest health benefits, study finds
August 13, 2018 - Scientists discover biomarker for kidney cancer
August 13, 2018 - New test predicts the risk of serious disease before symptoms appear
August 13, 2018 - Cianna Medical receives FDA 510(k) clearance to extend indication of SCOUT reflector for use in soft tissue localization
August 13, 2018 - Ground-breaking discovery offers new hope for treatment of Alzheimer’s, other neurological diseases
August 13, 2018 - Medical nutrition therapy provided by RDNs benefits patients with chronic kidney disease
August 13, 2018 - Prenatal Tdap vaccination not linked with increased risk of autism in children, study shows
August 13, 2018 - One-Third of Canadian Patients Get Hip Fx Repair Within 24 Hours
August 13, 2018 - ANA (Antinuclear Antibody) Test: MedlinePlus Lab Test Information
August 13, 2018 - Traffic jams in the brain
August 13, 2018 - NIH awards $6.5 million to establish multi-institution biomedical technology resource center
August 13, 2018 - New marker in the blood could help predict person’s risk of developing kidney cancer
August 13, 2018 - New biomarker may provide clues to create diagnostic tool for hypoglycemia-associated autonomic failure
August 13, 2018 - Oxidative Stress Hampers Blood Vessel Dilation in Men
August 13, 2018 - Parents’ Religious Beliefs May Affect Kids’ Suicide Risk: Study
August 13, 2018 - Measure of belly fat in older adults is linked with cognitive impairment
August 13, 2018 - FDA permits marketing of first mobile medical app for contraceptive use to prevent pregnancy
August 13, 2018 - NUS scientists develop new technology to customize optimal drug ‘cocktail’ for myeloma patients
August 13, 2018 - Disordered eating behaviors up for overweight young adults
August 13, 2018 - Connection between Alzheimer’s disease and degenerative eye diseases
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