Sequencing of The Developing Human Brain Uncovers Hundreds of Thousands of New Gene Transcripts - ScienceDaily

2024/5/26 15:11 Sequencing of the developing human brain uncovers hundreds of thousands of new gene transcripts | ScienceDaily
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Sequencing of the developing human brain uncovers Breaking this hour
hundreds of thousands of new gene transcripts

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Source: University of California - Los Angeles Health Sciences
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Summary: Researchers uncovered 214,516 unique isoforms in the developing neocor‐  Human Brain: New Gene Transcripts
tex -- over 70% of which have not been previously studied.
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HEALTH & MEDICINE
 Brain-Computer A team led by researchers at UCLA and the
Interfaces University of Pennsylvania has produced a first- Lymphoma
 Learning Disorders of-its kind catalog of gene-isoform variation in Immune System
 Brain Injury
the developing human brain. This novel dataset Anemia
provides crucial insights into the molecular basis MIND & BRAIN
 Disorders and
of neurodevelopmental and psychiatric brain Learning Disorders
Syndromes
disorders and paves the way for targeted
 Autism Child Psychology
therapies.
Parenting
 Intelligence
The research, published in Science, also details how tran‐ LIVING & WELL
 Child Development
script expression varies by cell type and maturity, finding
Parenting
 Neuroscience that changing gene-isoform expression levels can help us
Nutrition
better understand how the human brain develops.
RELATED TERMS Stress
Every cell in our body contains the same genetic informa‐
tion encoded in DNA, but it is the expression of different Strange & Offbeat
 Neocortex (brain)
proteins, encoded in mRNA transcripts, that give cells
 Memory-prediction their distinct functions. These varied proteins, or iso‐ HEALTH & MEDICINE
framework forms, mostly arise from alternative splicing -- a process

Imperceptible Sensors Made from 'Electronic
that is highly prevalent in the brain and contributes to its Spider Silk' Can Be Printed Directly on
 Retina wide range of proteins and characteristics. Human Skin
 List of cognitive biases Psychedelic Drug-Induced Hyperconnectivity

"We knew, based on our previous research, that isoform in the Brain Helps Clarify Altered Subjective
 Tipping point regulation is a key molecular feature for understanding Experiences
brain development and genetic risk for neuropsychiatric Robots' and Prosthetic Hands' Sense of
 Scientific method disorders," said Dr. Luis de la Torre-Ubieta of the Eli and Touch Could Be as Fast as Humans
Edythe Broad Center of Regenerative Medicine and Stem
 Cognition MIND & BRAIN
Cell Research at UCLA, who co-led the study alongside
 Carl Jung AI Headphones Let Wearer Listen to a Single
Person in a Crowd, by Looking at Them Just
Once
Dr. Michael Gandal, an associate professor of psychiatry Eurasian Jays Can Use 'Mental Time Travel'
Like Humans, Study Finds
and genetics in the Perelman School of Medicine at the
University of Pennsylvania. Some Mice May Owe Their Monogamy to a
Newly Evolved Type of Cell
Previously, despite its prevalence, the role of cell-type-
LIVING & WELL
specific splicing and transcript-isoform diversity in the
developing human brain had not been systematically in‐ Creating a Green Composite Material from
Japanese Washi Paper
vestigated due to limitations in prior generations of se‐
quencing technologies. Here, the researchers were able Coming out to a Chatbot?
to leverage new third-generation long-read sequencing Cats Purrfectly Demonstrate What It Takes to
technologies to capture complete RNA molecules and Trust Robots
profile the full-length transcriptome of two major regions
of the developing neocortex: the germinal zone, which
contains stem cells, and the cortical plate, which houses
newly generated neurons.
This technology allowed the researchers to uncover

214,516 unique isoforms -- over 70% of which have nev‐
er been previously studied. They then compared the two
regions of the developing brain and observed that
changes in isoform expression levels are important for
neurogenesis, differentiation and cell fate -- in essence,
the maturation of the brain.
The researchers found thousands of isoform switches

that occur during brain development, implicating previ‐
ously uncharacterized RNA-binding proteins in cellular
identity and cellular fate decisions. Their findings also elu‐
cidate genetic risk mechanisms for neurodevelopmental
and neuropsychiatric disorders, including a reassessment
of the significance and clinical relevance of thousands of
rare genetic variants.
"We found that high-confidence risk genes for autism or

neurodevelopmental disorders tend to be genes that have
more isoforms, and those isoforms are expressed differ‐
ently during neurogenesis," said de la Torre-Ubieta, an
assistant professor of psychiatry and behavioral sciences.
"This implies that dysregulation of the expression of spe‐
cific isoforms is a potential mechanism underlying these
disorders."
Scientists studying the brain often rely on publicly avail‐

able catalogs of genes and gene transcripts. However,
human brain tissue, particularly embryonic tissue, is diffi‐
cult to access, restricting the comprehensiveness of
these datasets. For this study, the researchers obtained
six developing human neocortex tissue samples repre‐
senting the mid-gestation period, or 15 to 17 weeks post-
conception. This developmental time point in the human
brain is a critical window during which the complexity of
our brain -- the most sophisticated organ in our body --
begins to emerge.
"These tissue samples enabled a striking level of novel

transcript discovery," Gandal said. "And because these
databases haven't incorporated or represented these crit‐
ical time points, we can dramatically expand our under‐
standing of how genes are regulated in the context of hu‐
man brain development."
The findings from the study have strong therapeutic impli‐

cations and could be clinically actionable, the researchers
said. Uncovering new transcripts could pave the way for
identifying novel treatment approaches in gene therapy
trials or targeted therapeutic trials for individuals harbor‐

ing rare mutations associated with psychiatric or neu‐
rodevelopmental disorders.
In the nearer term, the data also has direct implications in

improving our ability to make genetic diagnoses of neu‐
rodevelopmental disorders. Because the study found sev‐
eral thousand genetic variants that are more impactful
than previously thought, families or individuals carrying
those variants can better understand how their children
might be predisposed to certain disorders.
Gandal has shared the dataset with several colleagues at

the Children's Hospital of Philadelphia, which has a large
population of children with rare neurodevelopmental dis‐
orders or undiagnosed disorders in development.
Physicians there are already using this resource to help
better interpret neurogenetics diagnostically.
"I'm really excited to leverage this resource to help pa‐

tients," said Gandal, who is also a practicing psychiatrist.
"Having this knowledge brings us one step closer to be‐
ing able to develop targeted treatments and understand
genetic mechanisms in a much more specific way."
Other UCLA authors include Ashok Patowary, Pan Zhang,

Celine K. Vuong, Xinzhou Ge, Kangcheng Hou, Minsoo
Kim, Michael Margolis, Bogdan Pasaniuc and Jingyi
Jessica Li. Connor Jops, Naihua Gong, Daniel Vo,
Xusheng Wang and Chunyu Liu contributed to this study.
The research was supported by the Simons Foundation

Autism Research Initiative, the National Institute of Mental
Health, the National Science Foundation and the UCLA
Medical Scientist Training Program.
Story Source:
Materials provided by University of California - Los Angeles Health Sciences. Original

written by Ani Vahradyan. Note: Content may be edited for style and length.
Journal Reference:
1. Ashok Patowary, Pan Zhang, Connor Jops, Celine K. Vuong, Xinzhou Ge, Kangcheng
Hou, Minsoo Kim, Naihua Gong, Michael Margolis, Daniel Vo, Xusheng Wang,
Chunyu Liu, Bogdan Pasaniuc, Jingyi Jessica Li, Michael J. Gandal, Luis de la Torre-
Ubieta. Developmental isoform diversity in the human neocortex informs neu‐
ropsychiatric risk mechanisms. Science, 2024; 384 (6698) DOI: 10.1126/sci‐
ence.adh7688
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University of California - Los Angeles Health Sciences. "Sequencing of the developing

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240523205011.htm>.
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2024/5/26 15:11 Sequencing of the developing human brain uncovers hundreds of thousands of new gene transcripts | ScienceDaily

Your source for the latest research news

New! Sign up for our free email newsletter.

Science News from research organizations  Print  Email  Share

Sequencing of the developing human brain uncovers Breaking this hour

hundreds of thousands of new gene transcripts

 'Electronic Spider Silk' Printed On Human Skin

Share: abegd  Origins of the Proton's Spin

 Symbiotic Bacteria Communicate With Plants

 Learning Disorders of-its kind catalog of gene-isoform variation in Immune System

framework forms, mostly arise from alternative splicing -- a process

 List of cognitive biases Psychedelic Drug-Induced Hyperconnectivity

This technology allowed the researchers to uncover

The researchers found thousands of isoform switches

"We found that high-confidence risk genes for autism or

Scientists studying the brain often rely on publicly avail‐

"These tissue samples enabled a striking level of novel

The findings from the study have strong therapeutic impli‐

trials or targeted therapeutic trials for individuals harbor‐

In the nearer term, the data also has direct implications in

Gandal has shared the dataset with several colleagues at

"I'm really excited to leverage this resource to help pa‐

Other UCLA authors include Ashok Patowary, Pan Zhang,

The research was supported by the Simons Foundation

Medical Scientist Training Program.

Materials provided by University of California - Los Angeles Health Sciences. Original

Cite This Page:

University of California - Los Angeles Health Sciences. "Sequencing of the developing

Explore More from ScienceDaily

The Gene to Which We Owe Our Big Brain

Key Processes in Early Brain Development Revealed

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