Dystrophin deficiency impairs cell junction formation during embryonic myogenesis from pluripotent stem cells.
Mutations in the DMD gene lead to Duchenne muscular dystrophy (DMD), a severe neuromuscular disorder affecting young boys as they acquire motor functions. DMD is typically diagnosed at 2-4 years of age, but the absence of dystrophin has negative impacts on skeletal muscles before overt symptoms appear in patients, which poses a serious challenge in current standards of care. Here, we investigated the consequences of dystrophin deficiency during skeletal muscle development. We used single-cell transcriptome profiling to characterize the myogenic trajectory of human pluripotent stem cells and showed that DMD cells bifurcate to an alternative branch when they reach the somite stage. Dystrophin deficiency was linked to marked dysregulations of cell junction proteins involved in the cell state transitions characteristic of embryonic somitogenesis. Altogether, this work demonstrates that in vitro, dystrophin deficiency has deleterious effects on cell-cell communication during myogenic development, which should be considered in future therapeutic strategies for DMD.
Pubmed ID: 39040067 RIS Download
Research resources used in this publication
None foundAdditional research tools detected in this publication
- ATCC (RRID:SCR_001672)
- Fiji (RRID:SCR_002285)
- CRAN (RRID:SCR_003005)
- ZENODO (RRID:SCR_004129)
- STAR (RRID:SCR_004463)
- PRISM (RRID:SCR_005375)
- New England Biolabs (RRID:SCR_013517)
- ggplot2 (RRID:SCR_014601)
- bcl2fastq (RRID:SCR_015058)
- dplyr (RRID:SCR_016708)
- QuPath (RRID:SCR_018257)
- Monocle3 (RRID:SCR_018685)
Antibodies used in this publication
- GAPDH Antibody (RRID:AB_10001796)
- Mouse Anti-Human Dystrophin Monoclonal Antibody, Unconjugated Conjugated, Clone Dy8/6C5 (RRID:AB_442081)
- Polyclonal Rabbit Anti-Goat Immunoglobulins/HRP (RRID:AB_2617143)
- Goat Anti-Mouse Immunoglobulins/HRP (RRID:AB_2617137)
- Monoclonal Anti-alpha-Tubulin antibody produced in mouse (RRID:AB_477579)
- Vimentin Monoclonal Antibody (V9), eFluor™ 570, eBioscience (RRID:AB_11220476)
- CD324 (E-Cadherin) Monoclonal Antibody (DECMA-1), Alexa Fluor™ 488, eBioscience (RRID:AB_10671270)
- Monoclonal Anti-alpha-Actinin (Sarcomeric) antibody produced in mouse (RRID:AB_476766)
- myosin, sarcomere (MHC) antibody - Fischman, D.A.; Weill Cornell Medical College (RRID:AB_2147781)
- Donkey Anti-Goat IgG (H+L) Antibody, Alexa Fluor 488 Conjugated (RRID:AB_2534102)
- Goat anti-Mouse IgG2b Cross-Adsorbed Secondary Antibody, Alexa Fluor™ 555 (RRID:AB_2535783)
- Goat Anti-Human Hgf r Polyclonal antibody, Unconjugated (RRID:AB_355289)
Associated grants
- Agency: NIDDK NIH HHS, United States
Id: P30 DK017047 - Agency: NIAMS NIH HHS, United States
Id: U54 AR065139
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This is a list of tools and resources that we have found mentioned in this publication.
ATCC (tool)
RRID:SCR_001672
Global nonprofit biological resource center (BRC) and research organization that provides biological products, technical services and educational programs to private industry, government and academic organizations. Its mission is to acquire, authenticate, preserve, develop and distribute biological materials, information, technology, intellectual property and standards for the advancement and application of scientific knowledge. The primary purpose of ATCC is to use its resources and experience as a BRC to become the world leader in standard biological reference materials management, intellectual property resource management and translational research as applied to biomaterial development, standardization and certification. ATCC characterizes cell lines, bacteria, viruses, fungi and protozoa, as well as develops and evaluates assays and techniques for validating research resources and preserving and distributing biological materials to the public and private sector research communities.
View all literature mentionsFiji (tool)
RRID:SCR_002285
Software package as distribution of ImageJ and ImageJ2 together with Java, Java3D and plugins organized into coherent menu structure. Used to assist research in life sciences.
View all literature mentionsCRAN (tool)
RRID:SCR_003005
Network of ftp and web servers around world that store identical, up to date, versions of code and documentation for R. Package archive network for R programming language.
View all literature mentionsZENODO (tool)
RRID:SCR_004129
Repository for all research outputs from across all fields of science in any file format as well as both positive and negative results. They assign all publicly available uploads a Digital Object Identifier (DOI) to make the upload easily and uniquely citeable. They further support harvesting of all content via the OAI-PMH protocol. They promote peer-reviewed openly accessible research, and curate uploads. ZENODO allows users to create their own collection and accept or reject all uploads to it. They allow for uploading under a multitude of different licenses and access levels.
View all literature mentionsSTAR (tool)
RRID:SCR_004463
Software performing alignment of high-throughput RNA-seq data. Aligns RNA-seq reads to reference genome using uncompressed suffix arrays.
View all literature mentionsPRISM (tool)
RRID:SCR_005375
THIS RESOURCE IS NO LONGER IN SERVICE. Documented on May 5,2022.Tool that predicts interactions between transcription factors and their regulated genes from binding motifs. Understanding vertebrate development requires unraveling the cis-regulatory architecture of gene regulation. PRISM provides accurate genome-wide computational predictions of transcription factor binding sites for the human and mouse genomes, and integrates the predictions with GREAT to provide functional biological context. Together, accurate computational binding site prediction and GREAT produce for each transcription factor: 1. putative binding sites, 2. putative target genes, 3. putative biological roles of the transcription factor, and 4. putative cis-regulatory elements through which the factor regulates each target in each functional role.
View all literature mentionsggplot2 (tool)
RRID:SCR_014601
Open source software package for statistical programming language R to create plots based on grammar of graphics. Used for data visualization to break up graphs into semantic components such as scales and layers.
View all literature mentionsbcl2fastq (tool)
RRID:SCR_015058
Conversion software that both demultiplexes data and converts BCL files generated by Illumina sequencing systems to standard FASTQ file formats for downstream analysis.
View all literature mentionsdplyr (tool)
RRID:SCR_016708
Software tool for working with data frame like objects, both in memory and out of memory. It is a grammar of data manipulation, providing a consistent set of verbs that help you solve the most common data manipulation challenges: mutate, select, filer, summerise, arrange.
View all literature mentionsQuPath (tool)
RRID:SCR_018257
Open Source software package for digital pathology image analysis. Used for whole slide image analysis and digital pathology. Provides researchers with batch processing and scripting functionality, and extensible platform with which to develop and share new algorithms to analyze complex tissue images.
View all literature mentionsMonocle3 (tool)
RRID:SCR_018685
Software analysis toolkit for single cell RNA-seq. Used for single cell RNA-Seq experiments. Unsupervised algorithm that increases temporal resolution of transcriptome dynamics using single-cell RNA-Seq data collected at multiple time points.
View all literature mentionsGAPDH Antibody (antibody)
RRID:AB_10001796
This polyclonal targets GAPDH
View all literature mentionsMouse Anti-Human Dystrophin Monoclonal Antibody, Unconjugated Conjugated, Clone Dy8/6C5 (antibody)
RRID:AB_442081
This monoclonal targets Human Dystrophin
View all literature mentionsPolyclonal Rabbit Anti-Goat Immunoglobulins/HRP (antibody)
RRID:AB_2617143
This polyclonal targets Goat immunoglobulins of all classes
View all literature mentionsGoat Anti-Mouse Immunoglobulins/HRP (antibody)
RRID:AB_2617137
This polyclonal targets Immunoglobulins
View all literature mentionsMonoclonal Anti-alpha-Tubulin antibody produced in mouse (antibody)
RRID:AB_477579
This monoclonal targets α-tubulin
View all literature mentionsVimentin Monoclonal Antibody (V9), eFluor™ 570, eBioscience (antibody)
RRID:AB_11220476
This monoclonal targets Vimentin
View all literature mentionsCD324 (E-Cadherin) Monoclonal Antibody (DECMA-1), Alexa Fluor™ 488, eBioscience (antibody)
RRID:AB_10671270
This monoclonal targets CD324 (E-Cadherin)
View all literature mentionsMonoclonal Anti-alpha-Actinin (Sarcomeric) antibody produced in mouse (antibody)
RRID:AB_476766
This monoclonal targets alpha-Actinin (Sarcomeric)
View all literature mentionsmyosin, sarcomere (MHC) antibody - Fischman, D.A.; Weill Cornell Medical College (antibody)
RRID:AB_2147781
This monoclonal targets myosin, sarcomere (MHC)
View all literature mentionsDonkey Anti-Goat IgG (H+L) Antibody, Alexa Fluor 488 Conjugated (antibody)
RRID:AB_2534102
This unknown targets IgG (H+L)
View all literature mentionsGoat anti-Mouse IgG2b Cross-Adsorbed Secondary Antibody, Alexa Fluor™ 555 (antibody)
RRID:AB_2535783
This polyclonal secondary targets IgG2b
View all literature mentionsGoat Anti-Human Hgf r Polyclonal antibody, Unconjugated (antibody)
RRID:AB_355289
This polyclonal targets Human HGF R
View all literature mentions
