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Title:
Construction of developmental lineage relationships in the mouse mammary gland by single-cell RNA profiling | Nature Communications
Description:
The mammary epithelium comprises two primary cellular lineages, but the degree of heterogeneity within these compartments and their lineage relationships during development remain an open question. Here we report single-cell RNA profiling of mouse mammary epithelial cells spanning four developmental stages in the post-natal gland. Notably, the epithelium undergoes a large-scale shift in gene expression from a relatively homogeneous basal-like program in pre-puberty to distinct lineage-restricted programs in puberty. Interrogation of single-cell transcriptomes reveals different levels of diversity within the luminal and basal compartments, and identifies an early progenitor subset marked by CD55. Moreover, we uncover a luminal transit population and a rare mixed-lineage cluster amongst basal cells in the adult mammary gland. Together these findings point to a developmental hierarchy in which a basal-like gene expression program prevails in the early post-natal gland prior to the specification of distinct lineage signatures, and the presence of cellular intermediates that may serve as transit or lineage-primed cells. The mammary epithelium comprises two cell lineages but the heterogeneity amongst these during development is unclear. Here, the authors report single-cell RNA sequencing of the mouse mammary epithelium at four developmental stages, revealing diversity in both compartments and a transcriptional shift with puberty onset.
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cells, cell, genes, mammary, basal, luminal, pubmed, expression, fig, article, google, scholar, epithelial, cas, adult, gland, singlecell, gene, analysis, supplementary, glands, puberty, stem, clusters, population, cluster, lineage, nature, data, stages, prepubertal, central, developmental, pubertal, progenitor, mice, mouse, development, mixedlineage, scrnaseq, expressed, protein, intermediate, cancer, heterogeneity, molecular, fluidigm, weeks, krt, diestrus,
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nature portfolio privacy policy wnt/beta-catenin-responsive stem cells advertising separately index social media high-resolution scrna-seq analysis single-cell rna profiling single-cell transcriptomes reveals single-cell western blotting single-cell rna-seq reprints single-cell rna analyses open question middle medical research council single-cell datasets spanning mouse-human ortholog mapping generate tubular bi-layers reconstructing lineage hierarchies single-cell transcriptome data put single-cell studies single-cell qpcr method single-cell capture sites reveal basal lineage-priming apc anti-mouse cd31 apc anti-mouse cd45 multifactor rna-seq experiments reveal mixed-lineage clusters nanoliter-scale gel bead early post-natal gland largely hormone receptor-negative log2-rpkm values calculated post-natal mammary gland visualizing high-dimensional data post-natal gland development oncogenic yap-ccn2 pathways messenger rna level early post-natal cells high-resolution sequencing fluidigm c1 scrna-sequencing final libraries mixed-lineage states leading protein–protein interaction data early post-natal glands single-cell resolution 20 ng/ml cholera toxin single-cell suspensions distinct lineage-restricted programs freshly sorted lin–cd29locd24+
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headline:Construction of developmental lineage relationships in the mouse mammary gland by single-cell RNA profiling
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headline:Construction of developmental lineage relationships in the mouse mammary gland by single-cell RNA profiling
description:The mammary epithelium comprises two primary cellular lineages, but the degree of heterogeneity within these compartments and their lineage relationships during development remain an open question. Here we report single-cell RNA profiling of mouse mammary epithelial cells spanning four developmental stages in the post-natal gland. Notably, the epithelium undergoes a large-scale shift in gene expression from a relatively homogeneous basal-like program in pre-puberty to distinct lineage-restricted programs in puberty. Interrogation of single-cell transcriptomes reveals different levels of diversity within the luminal and basal compartments, and identifies an early progenitor subset marked by CD55. Moreover, we uncover a luminal transit population and a rare mixed-lineage cluster amongst basal cells in the adult mammary gland. Together these findings point to a developmental hierarchy in which a basal-like gene expression program prevails in the early post-natal gland prior to the specification of distinct lineage signatures, and the presence of cellular intermediates that may serve as transit or lineage-primed cells. The mammary epithelium comprises two cell lineages but the heterogeneity amongst these during development is unclear. Here, the authors report single-cell RNA sequencing of the mouse mammary epithelium at four developmental stages, revealing diversity in both compartments and a transcriptional shift with puberty onset.
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name:ACRF Stem Cells and Cancer Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia
type:PostalAddress
type:Organization
name:Lavinia Gordon
url:http://orcid.org/0000-0003-3469-8489
affiliation:
name:The Walter and Eliza Hall Institute of Medical Research
address:
name:Australian Genome Research Facility, The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia
type:PostalAddress
type:Organization
name:Anne C. Rios
affiliation:
name:The Walter and Eliza Hall Institute of Medical Research
address:
name:ACRF Stem Cells and Cancer Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia
type:PostalAddress
type:Organization
name:The University of Melbourne
address:
name:Department of Medical Biology, The University of Melbourne, Parkville, Australia
type:PostalAddress
type:Organization
name:Stephen Wilcox
affiliation:
name:The Walter and Eliza Hall Institute of Medical Research
address:
name:Systems Biology & Personalised Medicine Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia
type:PostalAddress
type:Organization
name:Naiyang Fu
affiliation:
name:The Walter and Eliza Hall Institute of Medical Research
address:
name:ACRF Stem Cells and Cancer Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia
type:PostalAddress
type:Organization
name:The University of Melbourne
address:
name:Department of Medical Biology, The University of Melbourne, Parkville, Australia
type:PostalAddress
type:Organization
name:Kevin He Liu
affiliation:
name:The Walter and Eliza Hall Institute of Medical Research
address:
name:ACRF Stem Cells and Cancer Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia
type:PostalAddress
type:Organization
name:Felicity C. Jackling
affiliation:
name:The Walter and Eliza Hall Institute of Medical Research
address:
name:ACRF Stem Cells and Cancer Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia
type:PostalAddress
type:Organization
name:Melissa J. Davis
affiliation:
name:The Walter and Eliza Hall Institute of Medical Research
address:
name:Bioinformatics Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia
type:PostalAddress
type:Organization
name:The University of Melbourne
address:
name:Department of Biochemistry and Molecular Biology, The University of Melbourne, Parkville, Australia
type:PostalAddress
type:Organization
name:Geoffrey J. Lindeman
url:http://orcid.org/0000-0001-9386-2416
affiliation:
name:The Walter and Eliza Hall Institute of Medical Research
address:
name:ACRF Stem Cells and Cancer Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia
type:PostalAddress
type:Organization
name:The University of Melbourne
address:
name:Department of Medicine, The University of Melbourne, Parkville, Australia
type:PostalAddress
type:Organization
name:The Royal Melbourne Hospital and Peter MacCallum Cancer Centre
address:
name:Parkville Familial Cancer Centre and Department of Medical Oncology, The Royal Melbourne Hospital and Peter MacCallum Cancer Centre, Parkville, Australia
type:PostalAddress
type:Organization
name:Gordon K. Smyth
url:http://orcid.org/0000-0001-9221-2892
affiliation:
name:The Walter and Eliza Hall Institute of Medical Research
address:
name:Bioinformatics Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia
type:PostalAddress
type:Organization
name:The University of Melbourne
address:
name:School of Mathematics and Statistics, The University of Melbourne, Parkville, Australia
type:PostalAddress
type:Organization
name:Jane E. Visvader
url:http://orcid.org/0000-0001-9173-6977
affiliation:
name:The Walter and Eliza Hall Institute of Medical Research
address:
name:ACRF Stem Cells and Cancer Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia
type:PostalAddress
type:Organization
name:The University of Melbourne
address:
name:Department of Medical Biology, The University of Melbourne, Parkville, Australia
type:PostalAddress
type:Organization
email:[email protected]
PostalAddress:
name:ACRF Stem Cells and Cancer Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia
name:Department of Medical Biology, The University of Melbourne, Parkville, Australia
name:Department of Medical Biology, The University of Melbourne, Parkville, Australia
name:Bioinformatics Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia
name:ACRF Stem Cells and Cancer Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia
name:Department of Medical Biology, The University of Melbourne, Parkville, Australia
name:ACRF Stem Cells and Cancer Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia
name:Australian Genome Research Facility, The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia
name:ACRF Stem Cells and Cancer Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia
name:Department of Medical Biology, The University of Melbourne, Parkville, Australia
name:Systems Biology & Personalised Medicine Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia
name:ACRF Stem Cells and Cancer Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia
name:Department of Medical Biology, The University of Melbourne, Parkville, Australia
name:ACRF Stem Cells and Cancer Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia
name:ACRF Stem Cells and Cancer Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia
name:Bioinformatics Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia
name:Department of Biochemistry and Molecular Biology, The University of Melbourne, Parkville, Australia
name:ACRF Stem Cells and Cancer Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia
name:Department of Medicine, The University of Melbourne, Parkville, Australia
name:Parkville Familial Cancer Centre and Department of Medical Oncology, The Royal Melbourne Hospital and Peter MacCallum Cancer Centre, Parkville, Australia
name:Bioinformatics Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia
name:School of Mathematics and Statistics, The University of Melbourne, Parkville, Australia
name:ACRF Stem Cells and Cancer Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia
name:Department of Medical Biology, The University of Melbourne, Parkville, Australia
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