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A single-cell time-lapse of mouse prenatal development from gastrula to birth.

Nature | 2024

The house mouse (Mus musculus) is an exceptional model system, combining genetic tractability with close evolutionary affinity to humans1,2. Mouse gestation lasts only 3 weeks, during which the genome orchestrates the astonishing transformation of a single-cell zygote into a free-living pup composed of more than 500 million cells. Here, to establish a global framework for exploring mammalian development, we applied optimized single-cell combinatorial indexing3 to profile the transcriptional states of 12.4 million nuclei from 83 embryos, precisely staged at 2- to 6-hour intervals spanning late gastrulation (embryonic day 8) to birth (postnatal day 0). From these data, we annotate hundreds of cell types and explore the ontogenesis of the posterior embryo during somitogenesis and of kidney, mesenchyme, retina and early neurons. We leverage the temporal resolution and sampling depth of these whole-embryo snapshots, together with published data4-8 from earlier timepoints, to construct a rooted tree of cell-type relationships that spans the entirety of prenatal development, from zygote to birth. Throughout this tree, we systematically nominate genes encoding transcription factors and other proteins as candidate drivers of the in vivo differentiation of hundreds of cell types. Remarkably, the most marked temporal shifts in cell states are observed within one hour of birth and presumably underlie the massive physiological adaptations that must accompany the successful transition of a mammalian fetus to life outside the womb.

Pubmed ID: 38355799 RIS Download

Research resources used in this publication

None found

Antibodies used in this publication

None found

Associated grants

  • Agency: NHGRI NIH HHS, United States
    Id: R01 HG010632
  • Agency: NHGRI NIH HHS, United States
    Id: UM1 HG011586
  • Agency: NIH HHS, United States
    Id: UM1 OD023222

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This is a list of tools and resources that we have found mentioned in this publication.


AnimalTFDB (tool)

RRID:SCR_001624

A comprehensive transcription factor (TF) database in which they identified and classified all the genome-wide TFs in 50 sequenced animal genomes (Ensembl release version 60). In addition to TFs, it also collects transcription co-factors and chromatin remodeling factors of those genomes, which play regulatory roles in transcription. Here they defined the TFs as proteins containing a sequence-specific DNA-binding domain (DBD) and regulating target gene expression. Currently, the AnimalTFDB classifies all the animal TFs into 72 families according to their conserved DBDs. Gene lists of transcription factors, transcription co-factors and chromatin remodeling factors of each species are available for downloading.

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STAR (tool)

RRID:SCR_004463

Software performing alignment of high-throughput RNA-seq data. Aligns RNA-seq reads to reference genome using uncompressed suffix arrays.

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HTSeq (tool)

RRID:SCR_005514

THIS RESOURCE IS NO LONGER IN SERVICE. Documented on February 28,2023. Software Python package that provides infrastructure to process data from high-throughput sequencing assays. While the main purpose of HTSeq is to allow you to write your own analysis scripts, customized to your needs, there are also a couple of stand-alone scripts for common tasks that can be used without any Python knowledge.

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Tangram (tool)

RRID:SCR_006152

A C / C++ command line toolbox for structural variation (SV) detection that reports mobile element insertions (MEI). It takes advantage of both read-pair and split-read algorithms and is extremely fast and memory-efficient. Powered by the Bamtools API, it can call SV events on multiple BAM files (a population) simutaneously to increase the sensitivity on low-coverage dataset.

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Mouse Genome Informatics (MGI) (tool)

RRID:SCR_006460

International database for laboratory mouse. Data offered by The Jackson Laboratory includes information on integrated genetic, genomic, and biological data. MGI creates and maintains integrated representation of mouse genetic, genomic, expression, and phenotype data and develops reference data set and consensus data views, synthesizes comparative genomic data between mouse and other mammals, maintains set of links and collaborations with other bioinformatics resources, develops and supports analysis and data submission tools, and provides technical support for database users. Projects contributing to this resource are: Mouse Genome Database (MGD) Project, Gene Expression Database (GXD) Project, Mouse Tumor Biology (MTB) Database Project, Gene Ontology (GO) Project at MGI, and MouseCyc Project at MGI.

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Trim Galore (tool)

RRID:SCR_011847

Software tool to automate quality and adapter trimming as well as quality control, with some added functionality to remove biased methylation positions for RRBS sequence files for directional, non-directional or paired-end sequencing. Wrapper around Cutadapt and FastQC to consistently apply adapter and quality trimming to FastQ files, with extra functionality for Reduced Representation Bisulfite Sequencing data.

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ggplot2 (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.

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bcl2fastq (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.

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