Release Date: 15 April 2022   ▪   Modified: 29 April 2024   ▪   Views: 761

Single-cell transcriptional landscape of human embryonic limb development

Data files
Download all files

Too many files!

You can download upto 1000 files at a time. For downloading a higher number of files, please use our alternative downloading methods.

  • Sarah Teichmann
    Sarah Teichmann
    Email: st9@sanger.ac.uk
    Role: investigator
    Affiliation: Wellcome Sanger Institute
    1
  • Peng He
    Peng He
    Email: brianpenghe@gmail.com
    Role: data analyst;submitter
    Affiliation: Wellcome Sanger Institute
    2
  • Hongbo Zhang
    Hongbo Zhang
    Email: zhanghongbo@mail.sysu.edu.cn
    Role: investigator
    Affiliation: Sun Yat-Sen University
    3
  • Bao Zhang
    Bao Zhang
    Email: zhangbao1991@hotmail.com
    Role: data analyst
    Affiliation: Sun Yat-Sen University
    4
  • Shuaiyu Wang
    Shuaiyu Wang
    Email: shuaiyu_wang@163.com
    Role: experiment performer
    Affiliation: Sun Yat-Sen University
    5
  • 1 Wellcome Sanger Institute
    Address: Wellcome Genome Campus, Hinxton, Saffron Walden CB10 1SA
  • 2 Wellcome Sanger Institute
    Address: Wellcome Genome Campus, Hinxton, Saffron Walden CB10 1SA
  • 3 Sun Yat-Sen University
    Address: 135 Xingang W Rd, Binjiang Road, Haizhu District, Guangzhou, Guangdong Province, China
  • 4 Sun Yat-Sen University
    Address: 135 Xingang W Rd, Binjiang Road, Haizhu District, Guangzhou, Guangdong Province, China
  • 5 Sun Yat-Sen University
    Address: 135 Xingang W Rd, Binjiang Road, Haizhu District, Guangzhou, Guangdong Province, China
AccessionE-MTAB-8813
Study typeRNA-seq of coding RNA from single cells efo
OrganismHomo sapiens
DescriptionHuman limbs emerge during the fourth post-conception week as mesenchymal buds, which develop into fully formed limbs over the subsequent months. This process is orchestrated by numerous temporally and spatially restricted gene expression programmes, making congenital alterations in phenotype common. Decades of work with model organisms have defined the fundamental mechanisms underlying vertebrate limb development, but an in-depth characterization of this process in humans has yet to be performed. Here we detail human embryonic limb development across space and time using single-cell and spatial transcriptomics. We demonstrate extensive diversification of cells from a few multipotent progenitors to myriad differentiated cell states, including several novel cell populations. We uncover two waves of human muscle development, each characterized by different cell states regulated by separate gene expression programmes, and identify musculin (MSC) as a key transcriptional repressor maintaining muscle stem cell identity. Through assembly of multiple anatomically continuous spatial transcriptomic samples using VisiumStitcher, we map cells across a sagittal section of a whole fetal hindlimb. We reveal a clear anatomical segregation between genes linked to brachydactyly and polysyndactyly, and uncover transcriptionally and spatially distinct populations of the mesenchyme in the autopod. Finally, we perform single-cell RNA sequencing on mouse embryonic limbs to facilitate cross-species developmental comparison, finding substantial homology between the two species.
Publication Bao Zhang, Peng He, John E. G. Lawrence, Shuaiyu Wang, Elizabeth Tuck, Brian A. Williams, Kenny Roberts, Vitalii Kleshchevnikov, Lira Mamanova, Liam Bolt, Krzysztof Polanski, Tong Li, Rasa Elmentaite, Eirini S. Fasouli, Martin Prete, Xiaoling He, Nadav Yayon, Yixi Fu, Hao Yang, Chen Liang, Hui Zhang, Raphael Blain, Alain Chedotal, David R. FitzPatrick, Helen Firth, Andrew Dean, Omer Ali Bayraktar, John C. Marioni, Roger A. Barker, Mekayla A. Storer, Barbara J. Wold, Hongbo Zhang & Sarah A. Teichmann. A human embryonic limb cell atlas resolved in space and time doi https://doi.org/10.1038/s41586-023-06806-x PMID 38057666
Human limbs emerge during the fourth post-conception week as mesenchymal buds, which develop into fully formed limbs over the subsequent months. This process is orchestrated by numerous temporally and spatially restricted gene expression programmes, making congenital alterations in phenotype common. Decades of work with model organisms have defined the fundamental mechanisms underlying vertebrate limb development, but an in-depth characterization of this process in humans has yet to be performed. Here we detail human embryonic limb development across space and time using single-cell and spatial transcriptomics. We demonstrate extensive diversification of cells from a few multipotent progenitors to myriad differentiated cell states, including several novel cell populations. We uncover two waves of human muscle development, each characterized by different cell states regulated by separate gene expression programmes, and identify musculin (MSC) as a key transcriptional repressor maintaining muscle stem cell identity. Through assembly of multiple anatomically continuous spatial transcriptomic samples using VisiumStitcher, we map cells across a sagittal section of a whole fetal hindlimb. We reveal a clear anatomical segregation between genes linked to brachydactyly and polysyndactyly, and uncover transcriptionally and spatially distinct populations of the mesenchyme in the autopod. Finally, we perform single-cell RNA sequencing on mouse embryonic limbs to facilitate cross-species developmental comparison, finding substantial homology between the two species.
Detailed sample information and links to data view table
Protocols show table
Samples
Sample count25
Experimental Designsdevelopment or differentiation design efo, cell type comparison design efo, cell component comparison design efo
Experimental Factorsindividual
Experimental Factors
Source Characteristics
Assays and Data
Assay count25
TechnologySequencing assay
Assay by MoleculeRNA assay
Processed Data
MAGE-TAB Files
MINSEQE Score
Exp. Design
Protocols
Variables
Processed
Raw