Breaking News
January 22, 2019 - Better mouse model built to enable precision-medicine research for Alzheimer’s
January 22, 2019 - Molecular profiling of precancerous lung lesions could lead to early detection and new treatments
January 22, 2019 - Genetic factors influence where fat is stored in our bodies
January 22, 2019 - The Psychology Behind Sticking to Your New Year’s Resolutions
January 22, 2019 - Scientists aim to find genetic causes of developmental abnormalities in the vagina and uterus
January 22, 2019 - Looming Global Crisis Means People’s Diets Must Change: Experts
January 22, 2019 - Excessive social media use is comparable to drug addiction
January 22, 2019 - Researchers show how mechanical stress affects bone development
January 22, 2019 - Study takes a step closer to understanding the body’s response to opioid painkillers
January 22, 2019 - Unexpected connection found between feeding and memory centers of the brain
January 22, 2019 - A revolutionary approach transforms bone trauma treatment
January 22, 2019 - Early studies and recent clinical trials on nerve growth factor
January 22, 2019 - Dry Mouth and Older Adults: Information for Caregivers
January 22, 2019 - Are your grandparents getting tipsy at the holiday party?
January 22, 2019 - New machine learning algorithms identify early symptoms of urinary tract infections
January 22, 2019 - Young women skipping the Pap smear test due to embarrassment
January 22, 2019 - A global influenza pandemic high on the WHO’s agenda
January 22, 2019 - Amgen Makes All Repatha (evolocumab) Device Options Available In The US At A 60 Percent Reduced List Price
January 22, 2019 - Elastronics—hydrogel-based microelectronics for localized low-voltage neuromodulation
January 22, 2019 - Branched-chain amino acids in tumors can be targeted to prevent and treat cancer
January 22, 2019 - Fueling macrophages with energy to attack and eat cancer cells
January 22, 2019 - Amgen And UCB Receive Positive Vote From FDA Advisory Committee In Favor Of Approval For Evenity (romosozumab)
January 22, 2019 - Does being bilingual make children more focused? Study says no
January 22, 2019 - Study reveals new genes and biological pathways linked to osteoarthritis
January 22, 2019 - FSU study provides better understanding of spinal cord injuries
January 22, 2019 - Delaying bath for newborn babies increases breastfeeding rates, finds study
January 21, 2019 - WHO identifies non-communicable diseases as major threat to human health
January 21, 2019 - Many parents still try non-evidence-based cold prevention methods for children
January 21, 2019 - High Levels of Activity, Motor Ability Linked to Better Cognition
January 21, 2019 - Killer blows? Knockout study of pair of mouse MicroRNA provides cancer insight
January 21, 2019 - Buffalo researchers receive grant to quicken development of generic equivalents of contraceptives
January 21, 2019 - One-third of pregnant women do not believe cannabis is harmful to their fetus
January 21, 2019 - Fiderstat could be used as chemopreventative drug for intestinal cancers caused by APC gene mutations
January 21, 2019 - Modifying healthcare delivery practices may improve discussions between youth and healthcare providers
January 21, 2019 - UNIST researcher named as recipient of Merck’s 2018 Life Science Awards
January 21, 2019 - How Getting a Flu Shot Could Save Your Life
January 21, 2019 - Surgical adhesions can be treated, prevented in mice
January 21, 2019 - Increased physician-targeted marketing associated with higher opioid overdose deaths
January 21, 2019 - Researchers uncover specific microbial signatures of intestinal disease
January 21, 2019 - Researchers discover new blood vessel system in bones
January 21, 2019 - Simple blood test reliably detects signs of Alzheimer’s damage before symptoms
January 21, 2019 - Study to investigate new targeted oral treatments for severe asthma
January 21, 2019 - Plan Your Plate | NIH News in Health
January 21, 2019 - Fecal occult blood test may improve CRC outcomes in some
January 21, 2019 - Blood test detects Alzheimer’s disease years before symptoms develop
January 21, 2019 - Mount Sinai joins with Paradigm and ReqMed to repurpose drug for treatment of MPS
January 21, 2019 - FDA Advisory Committee Votes on Zynquista (sotagliflozin) as Treatment for Adults with Type 1 Diabetes
January 21, 2019 - The causes and complications of snoring
January 21, 2019 - Placenta adapts and compensates when pregnant mothers have poor diets or low oxygen
January 21, 2019 - New implant could restore the transmission of electrical signals in injured central nervous system
January 21, 2019 - Rapid-acting fentanyl test strips found to be effective at reducing overdose risk
January 21, 2019 - Coronary Artery Calcium May Help Predict CVD in South Asians
January 21, 2019 - The mystery of the super-ager
January 21, 2019 - Scientists develop smart microrobots that can change shape depending on their surroundings
January 21, 2019 - Keep Moving to Keep Brain Sharp in Old Age
January 21, 2019 - Despite progress, gay fathers and their children still structurally stigmatized
January 21, 2019 - New drug for treating liver parasites in vivax malaria
January 21, 2019 - Merck recognized with 2018 Life Science Industry Award for best use of social media
January 21, 2019 - Coeur Wallis equips the canton of Valais with 260 SCHILLER defibrillators
January 21, 2019 - Scientists propose quick and pain-free method for diagnosing kidney cancer
January 21, 2019 - Signs of memory loss could point to hearing issues
January 21, 2019 - HeartFlow Analysis shows highest diagnostic performance for detecting coronary artery disease
January 21, 2019 - How Much Caffeine is Too Much?
January 21, 2019 - Take a timeout before you force your child to apologize
January 21, 2019 - Scientists design two AI algorithms to improve early detection of cognitive impairment
January 21, 2019 - Novel therapy for children with chronic hormone deficiency provides lifeline for parents
January 21, 2019 - Bioethicists call for oversight of poorly regulated, consumer-grade neurotechnology products
January 21, 2019 - Study shows hereditary hemochromatosis behind many cancers and joint diseases
January 21, 2019 - Short bouts of stairclimbing throughout the day can improve cardiovascular health
January 20, 2019 - Liver Transplant Survival May Improve With Race Matching
January 20, 2019 - Study implicates hyperactive immune system in aging brain disorders
January 20, 2019 - Cancer Diagnosis May Quadruple Suicide Risk
January 20, 2019 - Parkinson’s disease experts devise a roadmap
January 20, 2019 - Research brings new hope to treating degenerative brain diseases
January 20, 2019 - Scientists pinpoint a set of molecules that wire the body weight center of the brain
January 20, 2019 - Researchers get close to developing elusive blood test for Alzheimer’s disease
January 20, 2019 - UCLA researchers demonstrate new technique to develop cancer-fighting T cells
January 20, 2019 - Researchers discover how cancer cells avoid genetic meltdown
January 20, 2019 - Exercise makes even the ‘still overweight’ healthier: study
January 20, 2019 - University of Utah to establish first-of-its-kind dark sky studies minor in the US
Massively parallel single-nucleus RNA sequencing reveals insights into heart disease

Massively parallel single-nucleus RNA sequencing reveals insights into heart disease

image_pdfDownload PDFimage_print

CHOP Researcher: Massively Parallel Single-Nucleus Sequencing Offers Key Tool for Cardiac Biology and Heart Disease

Scientists using a powerful new technology that sequences RNA in 20,000 individual cell nuclei have uncovered new insights into biological events in heart disease. In animal studies, the researchers identified a broad variety of cell types in both healthy and diseased hearts, and investigated in rich detail the “transcriptional landscape,” in which DNA transfers genetic information into RNA and proteins.

“This is the first time to our knowledge that massively parallel single-nucleus RNA sequencing has been applied to postnatal mouse hearts, and it provides a wealth of detail about biological events in both normal heart development and heart disease,” said study leader Liming Pei, PhD, a molecular biologist in the Center for Mitochondrial and Epigenomic Medicine(CMEM) at Children’s Hospital of Philadelphia (CHOP) and an assistant professor in the Department of Pathology and Laboratory Medicine in the Perelman School of Medicine at the University of Pennsylvania. “Ultimately, our goal is to use this knowledge to discover new targeted treatments for heart disease. In addition, this type of large-scale sequencing may be broadly applied in many other fields of medicine.”

Pei and co-study leader HaoWu, PhD, also of the CMEM and an assistant professor of Genetics at Penn Medicine, published their findings online Sept. 25, 2018 in Genes & Development.

While massively parallel single-cell RNA sequencing (scRNA-seq) has been available to researchers in the past three years, it is technically challenging to study single cells in postnatal hearts due to the large size of cardiac muscle cells.

To enable single-cell analysis of large cells such as muscle cells, or cells with complex morphology such as neurons, robust massively parallel single-nucleus sequencing (snRNA-seq) methods have been developed recently in Wu’s laboratory, as well as by others in the field. To date, massively parallel snRNA-seq has been applied only to the central nervous system. Pei and colleagues are the first to adapt the technology for use in postnatal heart tissue.

The research team used the snRNA-Seq method termed sNucDrop-seq to analyze nearly 20,000 nuclei in heart tissue from normal and diseased mice. “We are excited to further develop sNucDrop-seq and apply it to mammalian postnatal hearts, which are of critical medical relevance but difficult to study with standard scRNA-seq,” said Wu.

The current study focused on cardiomyopathy, a group of diseases characterized by progressive weakening of the heart muscle, and representing aleading worldwide cause of heart failure. Pei and colleagues used mice developed to model a type of pediatric mitochondrial cardiomyopathy.

“The heart is a complex organ, with a multitude of cell types, and much still remains poorly understood about mammalian heart development and heart disease, especially during the postnatal period,” said Pei.“Our study provides key insights in three areas: normal heart development, heart disease, and gene regulatory mechanisms of a heart hormone called GDF15.”

The sequencing tool identified major types of heart cells, such as cardiomyocytes, fibroblasts and endothelial cells, as well as rarer cardiac cell types. The study team found great variety among each cell type, as well as indications of functional changes in the heart cells during both normal and diseased conditions. For example, the researchers detectedmetabolic changes in fibroblasts, the fibrous cells that make the heart abnormally stiff in heart disease.

Another finding concerned gene networks that regulate production of cardiac hormones in heart disease—specifically GDF15,which slows overallbody growth, presumably to reduce the energetic demands on a damaged heart. Such signaling, said Pei, could reveal more about the biological mechanisms that underlie the growth restriction commonly seen in children with congenital heart disease.

Greater understanding of cardiac biology, as provided in this research, said Pei, may lead to targeted therapies aimed at key gene networks that could offer better treatments for heart patients.

“This research was a first step in defining the transcriptional landscape of normal and diseased heart at high resolution,” said Pei, who added that future work in his and his collaborator’s laboratory will investigate how heart disease progresses over a longer timespan than the early postnatal period. The research tool may also offer opportunities to investigate diseases in organs and systems beyond the heart.

Source:

https://www.chop.edu/news/sequencing-20000-heart-cells-yields-insights-cardiac-disease

Tagged with:

About author

Related Articles