3-D organoids and RNA sequencing reveal the crosstalk driving lung cell formationSeptember 07, 2017
To stay healthy, our lungs have to maintain two key populations of cells: the alveolar epithelial cells, which make up the little sacs where gas exchange takes place, and bronchiolar epithelial cells (also known as airway cells) that are lined with smooth muscle.
"We asked, how does a stem cell know whether it wants to make an airway or an alveolar cell?" says Carla Kim, PhD, of the Stem Cell Research Program at Boston Children's Hospital.
Figuring this out could help in developing new treatments for such lung disorders as asthma and emphysema, manipulating the natural system for treatment purposes.
It's been widely assumed that epithelial stem cells direct the formation of these two cell types, but the picture turns out to be more complicated.
To investigate lung-cell formation, Kim and Joo-Hyeon Lee, PhD (now at the Cambridge Stem Cell Institute in the U.K.) used a 3D "organoid" culture system they established in 2014. This allowed them to observe what kinds of cells were being made.
To this, they added single-cell RNA sequencing to see what genes each cell type turns on. This enabled Kim and colleagues to identify what the cells are saying to each other.
As reported today in Cell, they found that lung cells known as mesenchymal cells (not to be confused with mesenchymal stem cells) are the cells driving the action. Through the single-cell RNA sequencing, they further found that mesenchymal cells come in at least five flavors, with different molecular signatures.
"All of these cell types are interacting with each other to repair and regenerate lung tissue," says Kim. "What we learned is that mesenchymal cells are telling the epithelial stem cells what type of lung cell they should make."
Cells with a marker called LGR5 secrete a lot of a molecule called Wnt5A that promotes the formation of alveolar cells, Kim's team showed, while cells with the LGR6 marker are important for repair of airway cells.
"If you have a disease like emphysema or bronchopulmonary dysplasia where alveolar cells are not being repaired, stimulating the WNT pathway could be important," says Kim. "When WNT is blocked, you get the alternate kind of cell. But if you add WNT back in, it goes back to usual."
For airway problems like asthma, blocking WNT or finding a way to boost the formation of LGR6-bearing cells could be approaches to explore to increase production of airway cells. "We found that if you injure mouse lungs so airway cells are killed off, you need LGR6+ cells to repair that kind of damage," Kim says.
But she acknowledges that there's much more to be learned.
"What we really want to know next is, what are all the secreted factors these cells make that can control cell fate? Those could be potential therapeutic targets."
Boston Children's Hospital
Related Asthma Articles:
A team of researchers from the University of Pittsburgh has found that insomnia is highly prevalent in adults with asthma and is also associated with worse asthma control, depression and anxiety symptoms and other quality of life and health issues.
A new study urges caution in the use of the mannitol challenge test for asthma in non-clinical settings.
Working with human immune cells in the laboratory, Johns Hopkins researchers report they have identified a critical cellular 'off' switch for the inflammatory immune response that contributes to lung-constricting asthma attacks.
Kids need flu shots to prevent asthma flares, and medications available in school to keep 86 percent in class, according to two studies being presented at the American College of Allergy, Asthma and Immunology Annual Scientific Meeting.
Scientists have made a discovery that could lead to improved treatment for asthma sufferers.
Defining a patient's symptoms using the historical diagnostic labels of asthma and chronic obstructive pulmonary disease (COPD) is an outdated approach to understanding an individual's condition, according to experts writing in the European Respiratory Journal today.
New research indicates that asthma in many adolescents is not likely to involve inflammation of the airways and therefore should not be considered an allergic disease.
Severe asthma can have a devastating effect on sufferers, affecting their ability to work or go to school and to lead normal lives.
Researchers may be closer to finding the mechanism responsible for loss of lung elastic recoil and airflow limitation in nonsmokers with chronic asthma.
New study in Annals of Allergy, Asthma and Immunology shows how an app directly connecting an allergist and an asthma sufferer can provide necessary intervention when asthma isn't under control.
Related Asthma Reading:
A Cure for Asthma?: What Your Doctor Isn't Telling You--and Why by David L. Hahn MD MS (2013) Paperback
by David L. Hahn MD MS (Author)
This book challenges conventional wisdom about the causes and treatments of asthma. Could hard-to-treat asthma be triggered by a persistent infection? Dr. David Hahn presents the scientific evidence and compelling case histories that led him to his surprising conclusion. He describes the treatment protocol he has used successfully. Find out if your asthma might be cured once and for all instead of managed. View Details
The Allergy and Asthma Cure: A Complete 8-Step Nutritional Program
by Fred Pescatore M.D. (Author)
Free yourself of allergies and asthma once and for all with Dr. Pescatore's breakthrough program
"" Dr. Fred Pescatore's The Allergy and Asthma Cure reveals a unique and revolutionary understanding of the underlying conditions of allergy and asthma-from food triggers to the environment to nutritional deficiencies. His integrative program of both alternative and traditional treatments can dramatically improve health and vitality, safely and soundly. This book will have a prominent place in my library and I highly recommend it! ""
-Ann Louise Gittleman, Ph.D., C.N.S., author of the... View Details
Breathe to Heal: Break Free From Asthma (Learn Buteyko) (Breathing Normalization)
by Sasha Yakovleva (Author), K.P. Buteyko MD-PhD (Author), A.E. Novozhilov MD (Author), Victor Lunn-Rockliffe (Illustrator), Arash Akhgari (Illustrator), Jane E. Brody (Illustrator), Thomas Fredricksen (Illustrator), Ira J. Packman (Illustrator), Jean Boles (Illustrator)
Understand Asthma & Breathing Problems. Stop fighting against asthma attacks and breathing difficulties! Say "Goodbye" to breathing problems! This book will help asthma sufferers to establish natural and wholesome breathing patterns and prevent asthma attacks. It will provide you with the information you need to tame your or your child's breathing difficulties naturally by improving the function of the respiratory system. It contains comprehensive instructions on the Breathing Normalization method based on the discovery by Dr. Buteyko in 1952 in Russia. Since then, this commonly called... View Details
Healing the New Childhood Epidemics: Autism, ADHD, Asthma, and Allergies: The Groundbreaking Program for the 4-A Disorders
by Kenneth Bock (Author), Cameron Stauth (Author)
Autism is an epidemic: It has spiked 1,500 percent in the last twenty years. ADHD, asthma and allergies have also skyrocketed over the same time period. One of these conditions now strikes one in every three children in America. But there is hope. Leading medical innovator Kenneth Bock, M.D., has helped change the lives of more than a thousand children, and in this important book, with a comprehensive program that targets all four of the 4-A disorders, he offers help to children everywhere. This is the book that finally puts hope within reach.
Doctors have generally overlooked the... View Details
Asthma For Dummies
by William E. Berger (Author), Jackie Joyner-Kersee (Foreword)
The incidence of asthma is rising dramatically in the United States and across the globe. Asthma affects 17 million people in the U.S. and is the most common chronic childhood disease. If you or someone you love suffers from asthma, you know that there is no cure—however, with proper care, asthmatics can lead normal, active, and fulfilling lives. Now you can breathe easy with this plain-English guide, which clearly explains the prevention, diagnosis, symptoms, and treatment of the disease.
Asthma For Dummies will help asthma sufferers and their loved ones get a strong handle on... View Details
Reversing Asthma: Breathe Easier with This Revolutionary New Program
by Richard N. Firshein (Author)
Comprehensive, balanced and up-to-the minute, Reversing Asthma is destined to be the new bible for asthma treatment - giving asthma sufferers new knowledge and new choices for overcoming this frightening and debilitating disease. View Details
Allergy and Asthma: Practical Diagnosis and Management (LANGE Clinical Medicine)
by Massoud Mahmoudi (Author)
Clear, authoritative guidance for your day-to-day allergy and asthma practice
Allergy and Asthma: Practical Diagnosis and Management is a concise guide that puts the most salient insights in allergy medicine right at your fingertips. Written by a leading allergy clinician, along with more than 40 nationally recognized expert contributors, this resource is perfect for front-line general practitioners, especially primary care physicians and allied health care providers. Inside, you'll find the most clinically relevant information on the pathophysiology, diagnosis,... View Details
ASTHMA: A Fresh Approach To Dealing With Asthma
by Ronnie Smith (Author)
What Everyone Needs To Know About This Fresh Approach To Dealing With Asthma... The most brilliant minds in the fields of health, medicine and psychology have tried and failed to find the solution to Asthma. Now, a new approach based on going back to nature rather than man-made medicine is gaining ground throughout the world. This "fresh approach" was initially laughed at and thought to be a joke. But when people started to have incredible results with it the laughter stopped. Now more and more research is gradually being done on this new nutritional approach to dealing with this... View Details
Asthma: Relax, You're Not Going to Die: Breathe More Easily with Safe and Effective Natural Therapies
by Jonathan M. Berkowitz (Author)
The natural approach presented in this handbook seeks to help sufferers of asthma to breathe more easily. While drugs have proved lifesaving for many people, the long-term answer for asthma sufferers is in learning how to embrace a healthy lifestyle. Jonathan Berkowitz shows how dietary changes, exercise, environmental controls, supplements and herbs can alleviate your symptoms safely and effectively, without the side effects of conventional drugs. Berkowitz is an asthmatic as well as a physician. View Details
Asthma: How To Get Asthma Free Naturally (asthma cure, asthma free naturally, asthma educator study guide, wheezing, asthma treatment, asthma attacks, hayfever)
by Vicki Joy (Author)
Do you suffer with asthma attacks? Are you looking for asthma treatment that can help you get asthma free naturally? Have you wondered if there is an asthma cure? This book is about natural remedies that can provide relief for asthma symptoms, and reduce the frequency and severity of asthma attacks. In this book you will learn about: What Is Asthma? What Causes An Asthma Attack? Asthma and Diet Natural Remedies for Asthma Over 20 million реорlе in thе United States can't tаkе brеаthing fоr granted because thеу аrе suffering from a chronic rеѕрirаtоrу аilmеnt саllеd... View Details