Brain organoids reveal neuronal flaws in syndrome tied to autism – Spectrum
Posted: October 13, 2020 at 11:57 am
Electric organoid: Neurons derived from people with 22q11.2 syndrome are hyperexcitable and show calcium-signaling deficits.
Courtesy of Pasca lab
Neurons derived from people with 22q11.2 deletion syndrome, a genetic condition linked to autism, show deficits in electrical activity and calcium signaling, according to a new study1. A single gene appears to be largely responsible for these defects, the study shows.
Up to 20 percent of people who lack part or all of the chromosomal region 22q11.2 have autism. Individuals with the deletion may also have schizophrenia, seizures, heart defects, immune dysfunction or learning problems.
The new findings uncover factors that may contribute to the development of psychiatric conditions associated with 22q11.2 deletion syndrome. They could also help researchers identify new therapeutic targets, says lead author Sergiu Pasca, associate professor of psychiatry and behavioral sciences at Stanford University in California.
The syndrome is relatively common, occurring in up to 1 in 4,000 newborns, Pasca says. But researchers do not fully understand how genes in the 22q11.2 region contribute to autism or other conditions, he adds.
To solve this molecular puzzle, Pasca and his team reprogrammed skin cells from 15 people with the deletion and 15 controls into induced pluripotent stem cells. Using a technique they developed in 2015, they coaxed these cells to turn into neurons, which self-organize in a dish into spherical clusters called organoids. The organoids show some key features of the developing cerebral cortex, a brain region implicated in autism.
The neurons derived from people with 22q11.2 syndrome spontaneously fire four times as frequently as neurons derived from controls, the researchers found. And the electrical activity of the 22q cells does not set off the usual spike in calcium levels, which is crucial for neurons to exchange messages.
In some other syndromes tied to schizophrenia and autism, calcium-channel genes are mutated. But the number of channels and the speed at which they work in 22q neurons is the same as in control neurons. Instead, the 22q cells show an unusually low voltage difference across the cell membrane when they arent firing, causing the signaling defects and hyperexcitability, the researchers found.
The researchers suspected that a gene called DGCR8 might be responsible for the neuronal deficits in the organoids because it lies within 22q11.2 and is linked to abnormal electrical activity in the neurons of mice2. DGCR8 is essential for the synthesis of short RNA fragments, called microRNAs, that regulate gene expression.
Lowering DGCR8s expression levels in control neurons reproduced the abnormalities seen in 22q neurons. In contrast, boosting the genes activity in 22q neurons or treating them with antipsychotic drugs prevented them from being overly excitable and reversed their calcium-signaling defects. The study was published 28 September in Nature Medicine.
Previous studies have analyzed lab-grown neurons derived from people with schizophrenia or autism-related disorders such as Rett and fragile X syndromes. But most used only a few human-derived cell lines, says Guo-li Ming, professor of neuroscience at the University of Pennsylvania in Philadelphia. The new study, Ming says, has a total of 30 human lines thats a huge effort.
By studying brain organoids derived from so many people, the researchers were able to identify the gene that might be involved in the psychiatric conditions associated with 22q11.2 syndrome, says Sally Temple, scientific director of the Neural Stem Cell Institute in Rensselaer, New York. Whenever we have a light shining ahead, saying, This is what you should really be looking at, it means that were making progress, she says.
The study participants with 22q11.2 syndrome vary in their psychiatric diagnoses, and yet all the brain organoids derived from their cells show the same neuronal abnormalities. Thats somewhat surprising, because we know there are a lot of differences in the genetic background of different people, Ming says.
The deletion might conspire with other factors to ultimately determine which psychiatric conditions a person has, Pasca says. It could be that the deletion causes cellular defects, and once there is a stressor such as social stress, disease develops. Its also unclear whether these cellular defects are related to the high prevalence of seizures in people with 22q11.2 syndrome, he says.
The hallmarks of most neuropsychiatric conditions can change over time, says Giuseppe Testa, director of the stem cell epigenetics unit at the European Institute of Oncology in Milan, Italy. Studies that look at a larger number of people with 22q11.2 deletion syndrome or other neurodevelopmental conditions could help to elucidate the relationship between the neuronal defects observed in the lab and the psychiatric manifestations of the conditions, Testa says. The new study, however, is a great resource for understanding how the 22q11.2 deletion contributes to schizophrenia and autism, he says.
Pascas team is trying to pinpoint molecules that could open new therapeutic avenues for 22q11.2 deletion syndrome. The antipsychotics they tested restore the unusual voltage differences in the 22q neurons, but they dont address the core mechanisms responsible for psychiatric conditions linked to the syndrome, Pasca says.
Whats more, antipsychotics have many side effects, and not all individuals respond to them, he says. We need better therapies we need to identify what the key molecular players are and target those.
Here is the original post:
Brain organoids reveal neuronal flaws in syndrome tied to autism - Spectrum
- A dive into the genetic history of India, and the role of vitamin A in skin repair - Science - March 12th, 2024
- Vitamin A could have a key role in both stem cell biology and wound healing: Study - Medical Dialogues - March 12th, 2024
- Fiona M. Watt receives the 2024 ISSCR Achievement Award for her seminal work with skin stem cells - EurekAlert - February 13th, 2024
- Eggs from men, sperm from women: Stem cell therapy may just turn reproduction upside down! - The Economic Times - January 20th, 2024
- Herbosa: Clinic under probe after skin treatments linked to womans death - Philstar.com - January 20th, 2024
- These Will Be the Biggest Skin-Care Trends of 2024 - Allure - December 25th, 2023
- Defence Mechanisms: Four ways your body is protecting you every time you fall sick - indulgexpress - May 13th, 2023
- Treat Yourself to a Spa Day With a $100 Deal on $600 Worth of Products From Elemis, 111SKIN, Nest & More - E! NEWS - May 13th, 2023
- Cell-Based Regenerative Medicine Market Size to Witness Rapid Growth at a CAGR of 15% by 2032 | insightSLICE - EIN News - May 5th, 2023
- Best EGF Serum (Epidermal Growth Factor Serum) In 2023: Discover the Ultimate In Skin Rejuvenation - Outlook India - April 18th, 2023
- 7-year-old vows to find a cure for brother in need of bone marrow transplant - WJLA - February 26th, 2023
- 10th Annual Regenerative Medicine Essentials Course and World Stem Cell Summit Return to Live with Virtual Option in 2023 - Newswise - February 10th, 2023
- Leukaemia signs and symptoms: How to detect, treat the aggressive blood cancer - Hindustan Times - February 10th, 2023
- Adult stem cell - Wikipedia - December 28th, 2022
- Stem cells: a brief history and outlook - Science in the News - December 28th, 2022
- What are totipotent stem cells & what can they do? - The Niche - December 28th, 2022
- Certain Foods Discovered to Increase Stem Cells, Cell Regeneration - December 28th, 2022
- Skin Cell - The Definitive Guide | Biology Dictionary - December 28th, 2022
- Women are using menstrual blood for skincare here's why I think beauty has gone too far this time - VOGUE India - December 4th, 2022
- Mesenchymal Stem Cells | Properties, Process, Functions, & Therapies - November 26th, 2022
- Childbirth - Wikipedia - November 26th, 2022
- Unlocking the Mysteries of Brain Regeneration Groundbreaking Study Offers New Insight - SciTechDaily - September 30th, 2022
- TikTok Made Me Buy It: The Creamy Concealer That Instantly Veils Dark Circles and Hyperpigmentation - Vogue - September 30th, 2022
- Here Is Why You Heal Slower As You Age - Health Digest - September 30th, 2022
- A glimpse into Indian consumers expectations for cosmetic treatments and consumption insights - The Financial Express - September 30th, 2022
- Propanc Biopharma Targets Pancreatic & Ovarian Cancers for PRP Clinical Studies with Combined Markets to Reach Over $14.3 Billion by 2027 -... - September 30th, 2022
- Hair-bearing human skin generated entirely from pluripotent stem cells - September 13th, 2022
- FACTORFIVE Skincare The Power of Stem Cells for Skin - September 13th, 2022
- Stem cells: Sources, types, and uses - Medical News Today - September 13th, 2022
- Hematopoietic Stem Cells | Hematopoiesis | Properties & Functions - September 13th, 2022
- Top 3 grants in regenerative medicine: July 2022 - RegMedNet - September 13th, 2022
- Beauty maybe be skin deep, but AI finds revenue on the faces surface - Biometric Update - September 13th, 2022
- September is Blood Cancer Awareness Month: All You Need to Know - News18 - September 13th, 2022
- 10 Facts That Prove Memory Is Not What You Think - Listverse - September 13th, 2022
- Seagen, Astellas and Merck Announce Results of Clinical Trial Investigating PADCEV (enfortumab vedotin-ejfv) with KEYTRUDA (pembrolizumab) and PADCEV... - September 13th, 2022
- NYC Dermatologist, Dr. Julie Russak, launches first Anti-Aging Wellness Program of its kind in the U.S. - PR Web - September 13th, 2022
- Curbing COVID-Related Hair Loss: Russak Dermatology's Hair Restoration Therapy - PR Web - August 11th, 2022
- Jennifer Aniston And Sandra Oh Swear By This Moisturizer That Shoppers Say Created Permanent Changes To Their Skin - Suggest - August 11th, 2022
- Victoria Beckham and Kim Kardashian are fans of Augustinus Baders skincare range - and you can get 20% off - The Mirror - August 11th, 2022
- How your intestines repair and renew themselves - Futurity: Research News - August 3rd, 2022
- Bone marrow imaging reveals the migration dynamics of neonatal hematopoietic stem cells | Communications Biology - Nature.com - August 3rd, 2022
- Global Stem Cells Group Expands Its Stem Cell Therapy and Regenerative Medicine Centers to Indonesia - GlobeNewswire - August 3rd, 2022
- NuFace Is Having a Major Sale During Amazon Prime Day 2022 See Deals on Trinity, NuBody, and More - Allure - July 17th, 2022
- Global Stem Cell Manufacturing Market Value Projected To Reach USD 21.71 Billion By 2029, Registering A CAGR Of 9.1% - Digital Journal - July 17th, 2022
- The 'Benjamin Button' effect: Scientists can reverse aging in mice. The goal is to do the same for humans - KITV Honolulu - July 17th, 2022
- Why do some women struggle to breastfeed? A UCSC researcher on what we know, and don't - Lookout Santa Cruz - July 17th, 2022
- What if we could genetically dial back our skin? - The Week - June 28th, 2022
- Reviewers Are Calling This Hydrating Stem Cell Cream Miraculous - Us Weekly - June 28th, 2022
- UVR Promotes Keratinocyte Phagocytosis and Skin Pigmentation Through T | CCID - Dove Medical Press - June 28th, 2022
- 'A new Alzheimer's treatment is on the horizon': Cell therapy reverses dementia-like syndrome in dogs - BioPharma-Reporter.com - June 28th, 2022
- What Is Vegan Collagen? And the 6 Best Products to Try - VegNews - June 28th, 2022
- Shock Wave Uses and Benefits The Horse - TheHorse.com - June 28th, 2022
- Chao Discusses Stratifying and Treating Patients With Graft-Vs-Host Disease - Targeted Oncology - June 28th, 2022
- Elucidating the developmental origin of life-sustaining adrenal glands | Penn Today - Penn Today - May 24th, 2022
- All Things Hot In The Beauty Space In The Month Of May | Femina.in - Femina - May 24th, 2022
- Anti-Aging Products and Therapies Market Size Estimated to Reach $93.2 Billion by 2027 - Digital Journal - April 2nd, 2022
- Learning from the single cell: A new technique to unravel gene regulation - EurekAlert - April 2nd, 2022
- Sailing the Genome in Search of Safe Harbors - Technology Networks - April 2nd, 2022
- 7 Easy Ways to Transition Your Skin Care Routine for Spring - Vancouver Magazine - April 2nd, 2022
- INTERNATIONAL STEM CELL CORP MANAGEMENT'S DISCUSSION AND ANALYSIS OF FINANCIAL CONDITION AND RESULTS OF OPERATIONS (form 10-K) - Marketscreener.com - April 2nd, 2022
- Syrian refugee is thriving five years after last-gasp gene therapy - STAT - STAT - December 9th, 2021
- Benefits of Pulsed Laser-based Skin Therapy - Newswise - December 9th, 2021
- Mesoblast has long been the one poster child for stem cell therapy. Now Cynata and other ASX stocks have e ... - Stockhead - December 9th, 2021
- In This Issue - pnas.org - December 9th, 2021
- UNM research team finds lungfish cocoon is living tissue with antimicrobial functions - UNM Newsroom - December 9th, 2021
- Mini-brain model of frontotemporal dementia demonstrates the stages of dysfunction that lead to cell death - National Institute on Aging - November 7th, 2021
- A major research project to advance regenerative therapy for epidermolysis bullosa (EB) using transgenic stem cells - PR Web - November 7th, 2021
- 15 Best Peptide Skin-Care Products 2021 for Smoother, Firmer, and Plumper Skin - Allure - November 7th, 2021
- Lab-Growing Everything Might Be The Only Way To Attain A Sustainable World - Intelligent Living - November 7th, 2021
- Common But Overlooked Causes for Hair Loss - The Cherokee Scout - November 7th, 2021
- How To Look Less Tired According To Experts | Grazia - Grazia - November 7th, 2021
- Losing Your Hair? You Might Blame the Great Stem Cell Escape. - The New York Times - October 5th, 2021
- Stem cells may be the key to saving white rhinos from extinction - Sciworthy - October 5th, 2021
- The Best Skincare Treatments For Time-Crunched Moms (Or Anyone Else Who Only Has Five Minutes To Spare) - Forbes - October 5th, 2021
- Stanford neuroscientist's 'assembloids' pave the way for innovative brain research - Scope - October 5th, 2021
- 3 of the Best Fall Beauty Buys - Pursuitist - October 5th, 2021
- Can Obesity Lead to Hair Fall? Here's What The Research Says - India.com - October 5th, 2021
- 12 of the best face serums 2021 - Medical News Today - October 5th, 2021
- The Number 1 Serum in the U.S. Is on Sale at SaksAlong With Other Never-Discounted Buys - Well+Good - October 5th, 2021
- Man discovers nasty red rash on his hands and elbows is potentially fatal - The Mirror - October 5th, 2021