Breaking News
December 10, 2018 - UC San Diego professor receives NCI Outstanding Investigator Award for cancer research
December 10, 2018 - Study evaluates placental mesenchymal stem cell sheets for myocardial repair and regeneration
December 10, 2018 - Blueprint Medicines Announces Updated Results from Ongoing EXPLORER Clinical Trial of Avapritinib Demonstrating Broad Clinical Activity and Significant Symptom Reductions in Patients with Systemic Mastocytosis
December 10, 2018 - Study clarifies ApoE4’s role in dementia
December 10, 2018 - Neuronal activity in the brain allows prediction of risky or safe decisions
December 10, 2018 - FDA Alerts Health Care Professionals and Patients Not to Use Drug Products Intended to be Sterile from Promise Pharmacy
December 10, 2018 - Improving dementia care and treatment saves thousands of pounds in care homes
December 10, 2018 - Heroin-assisted treatment can offer benefits, reduce harms
December 10, 2018 - People covered by Michigan’s expanded Medicaid program report improvements in health, finds study
December 10, 2018 - Hazelnuts improve micronutrient levels in older adults
December 9, 2018 - History of Partner Violence Tied to Menopause Symptoms
December 9, 2018 - Clean Up Safely After a Disaster|Natural Disasters and Severe Weather
December 9, 2018 - Drug wholesalers drove fentanyl’s deadly rise, report concludes
December 9, 2018 - Deprescribing could help manage polypharmacy in older adults
December 9, 2018 - Retraction of article “Joy of cooking too much” from journal
December 9, 2018 - FDA Warns of Rare Stroke Risk With MS Drug Lemtrada (Alemtuzumab)
December 9, 2018 - Feds say heroin, fentanyl remain biggest drug threat to US
December 9, 2018 - Eliminating microglia can reverse some aspects of stress sensitization, study shows
December 9, 2018 - New genetic insight could help treat rare debilitating heart and lung condition
December 9, 2018 - MiRagen Therapeutics Announces Final Safety, Biodistribution and Clinical Efficacy Data From Phase 1 Cobomarsen Clinical Trial in Patients With Mycosis Fungoides
December 9, 2018 - Work with your doctor to weigh pros, cons of treatment options for hyperthyroidism
December 9, 2018 - CWRU researcher secures $14.6 million funding for genetic study into Alzheimer’s disease
December 9, 2018 - High intensity statin treatment and adherence could save more lives
December 9, 2018 - Surgery patients use only 1/4 of prescribed opioids, and prescription size matters
December 9, 2018 - AXT offers Phi Optics upgrade to QPI systems for inverted light microscopes
December 9, 2018 - New booklet could help improve conditions of young pupils with albinism
December 9, 2018 - Few Physicians Work in Practices That Use Telemedicine
December 9, 2018 - Older Adults and Oral Health
December 9, 2018 - Health utility values improve after septorhinoplasty
December 9, 2018 - New EU-funded project provides insight into how the brain develops
December 9, 2018 - Expanded use of tele-emergency services can help strengthen rural hospitals
December 9, 2018 - Infections in the Young May Be Tied to Risk for Mental Illness: Study
December 9, 2018 - Profile: Native Hawaiians and Pacific Islanders
December 9, 2018 - Snoring poses greater cardiac risk to women
December 9, 2018 - Researcher takes further steps in understanding how and why cute aggression occurs
December 9, 2018 - Researchers create new light-activated tools for controlling neurons
December 9, 2018 - Spinal cord injury disrupts the body’s internal clock, study shows
December 9, 2018 - Babies recognize nested structures similar to our grammar
December 9, 2018 - UT Austin researcher receives $2.5 million CZI grant for neurodegenerative disease research
December 9, 2018 - Sleep problems found to be prevalent and increasing among college students
December 9, 2018 - Study reveals why some children are susceptible to the effects of maltreatment
December 9, 2018 - Study investigates influence of different opioids on driving performance
December 9, 2018 - Jazz Pharmaceuticals Announces First Patient Enrolled in Phase 3 Clinical Trial Evaluating JZP-258 for the Treatment of Idiopathic Hypersomnia
December 9, 2018 - Eliminating microglia prevents heightened immune sensitivity after stress
December 9, 2018 - Boys with social difficulties are at greatest risk of early substance use
December 9, 2018 - ‘Wrong’ connective tissue cells linked to worse prognosis in breast cancer patients
December 8, 2018 - Chronic, refractory schizophrenia patients benefit from targeted cognitive training
December 8, 2018 - Advertising in kids’ apps more prevalent than parents may realize
December 8, 2018 - New way to trace the transmission histories of rare genetic diseases
December 8, 2018 - ASH: A+CHP Bests CHOP for Peripheral T-Cell Lymphoma
December 8, 2018 - Results of pediatric genomic epilepsy tests often reclassified
December 8, 2018 - New way of controlling HIV latency to completely eradicate the virus
December 8, 2018 - Phasefocus to showcase the Livecyte 2 at ASCB
December 8, 2018 - KHN’s ‘What the Health?’ Is health spending the next big political issue?
December 8, 2018 - Mussels take in microplastic pollution fibers and flush most of them out again
December 8, 2018 - AHA: How to Stop Smoking … for Good
December 8, 2018 - Scientists overturn odds to make Parkinson’s discovery
December 8, 2018 - Health benefits of producing marula vinegar
December 8, 2018 - Failure of critical cellular energy sensor responsible for CKD progression, study finds
December 8, 2018 - Ethnicity can be reliable indicator of gut microbiota diversity
December 8, 2018 - Safe Sleep for Baby | NIH News in Health
December 8, 2018 - Study looks at ways technology can support nutritional needs of Parkinson’s patients
December 8, 2018 - Infant milk allergy is being overdiagnosed say experts
December 8, 2018 - Graphene may one day be used to test for ALS
December 8, 2018 - Houston Methodist launches real-time website to track flu cases
December 8, 2018 - RedHill Announces Positive Top-Line Results from Confirmatory Phase 3 Study with Talicia for H. pylori Infection
December 8, 2018 - A way to measure obesity and health beyond BMI
December 8, 2018 - New diagnostic tools may help identify breast cancer patients who could benefit from targeted therapies
December 8, 2018 - Duke-NUS researchers highlight possible role of bioaerosol sampling in pandemic surveillance
December 8, 2018 - Study quantifies links between alcohol, drug use and violent deaths
December 8, 2018 - Mothers’ stress levels at conception linked to child’s response to life challenges at age 11
December 8, 2018 - MIT researchers develop antimicrobial peptides from South American wasp’s venom
December 8, 2018 - Obesity prevention among low-income, diverse preschool-aged children and parents
December 8, 2018 - Mount Sinai researcher awarded $2.5 million to advance understanding of neurodegenerative diseases
December 8, 2018 - CZI announces funding for open-source software efforts to improve image analysis in biomedicine
December 8, 2018 - New book encompasses the vast history of reproduction
December 8, 2018 - Low-income women in Texas are not receiving contraception after childbirth, study shows
December 8, 2018 - Study expands knowledge about sexuality and gender gaps in political attitudes
December 8, 2018 - Drug reduces hot flash frequency, improves quality of life in breast cancer survivors
December 8, 2018 - Imaging, Biopsy Often Still Needed After Mastectomy
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