Breaking News
April 25, 2019 - The Current issue of “The view from here” is concerned with Partnerships and Alliances
April 25, 2019 - Imaging method reveals long-lived patterns in cells of the eye
April 25, 2019 - Podcast: KHN’s ‘What The Health?’ The Abortion Wars Rage On
April 25, 2019 - Prolonged exposure therapy is more effective in treating veterans with PTSD, alcohol use disorder
April 24, 2019 - Our artificial cornea breakthrough could lead to self-assembling organs
April 24, 2019 - A Stanford black, female, gay surgery resident speaks out
April 24, 2019 - Donna Lynne on Extreme Sports, Lessons From the '60s, and Taking CUIMC to the Next Level
April 24, 2019 - Pain Clinics’ Doctors Needlessly Tested Hundreds Of Urine Samples, Court Records Show
April 24, 2019 - Researchers uncover potential clue to halt destruction of nerve cells in people with ALS
April 24, 2019 - Study uncovers reasons for poor mental health in bisexual people
April 24, 2019 - Screenings, interventions, and referrals can help adolescents overcome substance abuse
April 24, 2019 - Febrile seizures following vaccination are self-resolving and not dangerous
April 24, 2019 - Flow-UV inline UV-Visible spectrometer monitors dispersion in real time
April 24, 2019 - Rates of Marijuana Use in Cancer Patients on the Rise in U.S.
April 24, 2019 - Versatile drug may protect baby from hazards of intraamniotic infections
April 24, 2019 - Financial transparency may diminish trust in doctors, new study finds
April 24, 2019 - Calling all Riders: Velocity Extends Free Registration 
April 24, 2019 - The Homeless Are Dying In Record Numbers On The Streets Of L.A.
April 24, 2019 - Blocking BRAF ubiquitination may be an effective treatment approach in melanoma
April 24, 2019 - Simple mobility test helps predict hospital readmission in elderly heart attack patients
April 24, 2019 - Novel fluorescence imaging system helps surgeons remove small ovarian tumors
April 24, 2019 - Uncovering the Structure of HIV Integrase to Inform Drug Discovery
April 24, 2019 - Medical Marijuana Use Rising Among Cancer Patients
April 24, 2019 - Artificial intelligence approach optimizes embryo selection for IVF
April 24, 2019 - Doctor or detective? Sleuthing mysteries in medical school
April 24, 2019 - CUIMC Community Gives Blood During Spring 2019 Columbia University Blood Drive
April 24, 2019 - Americans Overwhelmingly Want Federal Protections Against Surprise Medical Bills
April 24, 2019 - Making Laboratories More Efficient with the Most Modern LIMS on the Market
April 24, 2019 - Treating cancer patients with personalized, combination therapies improves outcomes
April 24, 2019 - Researchers engineer new molecules to help stop lung cancer
April 24, 2019 - Acupuncture can be a wonderful tool for preventing number of diseases
April 24, 2019 - Daily life disability before hip replacement may predict poor post-operative outcomes
April 24, 2019 - Study finds involuntary staying in housing estates to be a potential health risk
April 24, 2019 - Older kidney disease patients starting dialysis die at higher rates than previously thought
April 24, 2019 - Time-restricted eating shows promise for controlling blood glucose levels
April 24, 2019 - Ambiguous genitalia in newborns may be more common than previously thought
April 24, 2019 - Research provides important insight on the brain-body connection
April 24, 2019 - In 10 Years, Half Of Middle-Income Elders Won’t Be Able To Afford Housing, Medical Care
April 24, 2019 - Researchers study how E. coli clones have become major cause of drug-resistant infections
April 24, 2019 - Bacterial and fungal toxins found in popular electronic cigarettes
April 24, 2019 - Factors affecting absorption of ‘sunshine vitamin’ during spring/summer months
April 24, 2019 - Texting helps improve medication adherence, health outcomes for patients with schizophrenia
April 24, 2019 - Cochrane Review looks at different ways to use nicotine replacement therapies
April 24, 2019 - New review on relationship between COPD and Type 2 diabetes
April 24, 2019 - Brain areas linked to memory and emotion aid odor navigation in humans
April 24, 2019 - Brain stimulation reverses age-related memory loss
April 24, 2019 - Amid Opioid Prescriber Crackdown, Health Officials Reach Out To Pain Patients
April 24, 2019 - $4 million NIH award will help establish UCI Skin Biology Resource-based Center
April 24, 2019 - Cancer drugs reprogram genes in breast tumors to prevent endocrine resistance, finds study
April 24, 2019 - Combination-imaging technique provides new window into macaque brain connections
April 24, 2019 - Researchers identify new allergen responsible for allergy to durum wheat
April 24, 2019 - Researchers define role of rare, influential cells in the bone marrow
April 24, 2019 - DNA rearrangement may predict poor outcomes in multiple myeloma
April 24, 2019 - FDA Approves Skyrizi (risankizumab-rzaa) for Moderate to Severe Plaque Psoriasis
April 24, 2019 - Combination therapy might be beneficial in schizophrenia
April 24, 2019 - Blood test can help match cancer patients to early phase clinical trials
April 24, 2019 - Women tend to underreport snoring and underestimate its loudness
April 24, 2019 - Comprehensive molecular test introduced for diagnosis of malaria caused by P. vivax parasites
April 24, 2019 - New range prediction approach increases accuracy, safety and tolerability of proton therapy
April 24, 2019 - Need for Sedation Up for Regular Cannabis Users
April 24, 2019 - Lack of access to antibiotics is a major global health challenge
April 24, 2019 - New study provides better understanding on safety of deworming programs
April 24, 2019 - EEG used to detect impact of maternal stress on neurodevelopment in 2-month-old infants
April 24, 2019 - FDA Approves First Generic Naloxone Nasal Spray Against Opioid Overdose
April 24, 2019 - A new way of finding compounds that prevent aging
April 24, 2019 - Mechanical training makes synthetic hydrogels perform more like muscle
April 24, 2019 - Study provides new insights into regulatory T cells’ role in protecting against autoimmune disease
April 24, 2019 - Pregnant women with type 1 diabetes are at greater risk of preterm birth
April 24, 2019 - ‘Tummy tuck’ can be safely performed in obese patients with no increase in complications
April 23, 2019 - ‘First’ 3-D print of heart with human tissue, vessels unveiled
April 23, 2019 - Which blood-based method works best to detect TB?
April 23, 2019 - Gene therapy cures infants suffering from ‘bubble boy’ immune disease
April 23, 2019 - Chemical-sampling wristbands detect similar exposures across three continents
April 23, 2019 - Management of Residual Limb Pain
April 23, 2019 - Molecular clock influences immune cell responses
April 23, 2019 - On the importance of culture, partnerships and diversity at the Dean’s Lecture Series
April 23, 2019 - Siddhartha Mukherjee Receives Lewis Thomas Prize for Writing About Science
April 23, 2019 - Dengue mosquito poses greatest danger of spreading Zika virus in Australia
April 23, 2019 - Scientists identify 104 high-risk genes for schizophrenia
April 23, 2019 - Abdominal etching can help patients to get classic ‘six-pack abs’ physique
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