Cell reports

Using Stem Cell Models to Study Heart Disease Caused by RBM20 Deficiency and Finding That Increasing RBM20 May Help Treatment

CRISPR Gene Editing Weekly Brief ↗PubMed ↗DOI ↗

Updated

Abstract

Three RBM20 mutations were introduced into induced pluripotent stem cells, leading to impaired function in heart cells derived from these mutations.

  • iPSC-derived heart cells exhibited defects in splicing of RBM20 target genes, calcium handling, and contractility, mirroring symptoms of dilated cardiomyopathy.
  • A specific mutation, Pro633Leu, was identified as disease-causing based on exome sequencing of patient genomes and displayed similar cardiac dysfunction.
  • Treatment with all-trans retinoic acid increased RBM20 expression and corrected the observed defects in splicing, calcium handling, and contractility in heart cells with RBM20 mutations.
  • Pharmacological upregulation of RBM20 could represent a potential therapeutic approach for patients with specific RBM20 mutations associated with dilated cardiomyopathy.

Simplified

Full Text

We can’t show the full text here under this license.
View Full Text ↗

Funding

Competing interests

Declaration of Interests L.M.S. is co-founder and shareholder of Sophia Genetics. F.B., H.S., W.W., and L.M.S. have submitted a patent application on “Methods of treatment, genetic screening, and disease models for heart conditions associated with RBM20 deficiency.” M.M. is a shareholder of Vala Science.
PubMed

Related papers

Sep '17
Severe heart muscle disease caused by RBM20 S635A mutation modeled using patient stem cell–derived heart cells
top 10% journal
cited by 101 papers
research support, non-u.s. gov't
Nov '15
Using human stem cells to model heart muscle structure and function problems in inherited RBM20 dilated cardiomyopathy
cited by 90 papers
research support, n.i.h., extramural
Nov '22
Accurate gene editing of harmful RBM20 mutations improves dilated heart disease
top 1% journal
cited by 141 papers
research support, n.i.h., extramural
Jun '22
Targeting serine production as a new treatment approach for enlarged heart disease
top 1% journal
cited by 65 papers
research support, n.i.h., extramural

What Lands in Your Inbox Each Week:

  • 📚7 fresh studies
  • 📝plain-language summaries
  • ✅direct links to original studies
  • 🏅top journal indicators
  • 📅weekly delivery
  • 🧘‍♂️always free

Recent issues from the crispr gene editing brief

issue #49
A base editor corrected a dangerous immune mutation with 90% efficiency in patient stem cells
6 days ago7 studies
issue #48
CRISPR base editors delivered to rat brains reduced Huntington's protein fragments and improved movement
1 week ago7 studies
issue #47
AI tool uses AlphaFold3 to pinpoint exactly which gene editor residues cause off-target cuts
2 weeks ago7 studies
issue #46
A new delivery trick pushed prime editing efficiency up to 2.9-fold without extra off-target edits
3 weeks ago7 studies
issue #45
Scientists built humanized antibody mice in 8 weeks instead of over a year
4 weeks ago7 studies
issue #44
Scientists mapped 11,692 gene knockdowns in stem cells — all in one atlas
5 weeks ago7 studies
issue #43
A rat virus enzyme boosted gene editing efficiency by 1.88x at hard-to-edit DNA sites
6 weeks ago7 studies
issue #42
A single dose edited 49% of liver cells in mice — without a virus
7 weeks ago7 studies
issue #41
CRISPR gene therapy eliminates blood transfusions in 91% of β-thalassemia patients
8 weeks ago7 studies
issue #40
90% of CRISPR guide RNA modified with new chemistry maintains full gene editing power
9 weeks ago7 studies
explore the archive
See more issues from the crispr gene editing brief