Characterization of primary mammary epithelial cells with loss of BRCA1at a single cell level

Abstract Background Heterogeneity within the mouse mammary epithelium and potential lineage relationships have been recently explored by single-cell RNA profiling. To further understand how cellular diversity changes during mammary ontogeny, we profiled single cells from nine different developmental stages spanning late embryogenesis, early postnatal, prepuberty, adult, mid-pregnancy, late-pregnancy, and post-involution, as well as the transcriptomes of micro-dissected terminal end buds (TEBs) and subtending ducts during puberty. Methods The single cell transcriptomes of 132,599 mammary epithelial cells from 9 different developmental stages were determined on the 10x Genomics Chromium platform, and integrative analyses were performed to compare specific time points. Results The mammary rudiment at E18.5 closely aligned with the basal lineage, while prepubertal epithelial cells exhibited lineage segregation but to a less differentiated state than their adult counterparts. Comparison of micro-dissected TEBs versus ducts showed that luminal cells within TEBs harbored intermediate expression profiles. Ductal basal cells exhibited increased chromatin accessibility of luminal genes compared to their TEB counterparts suggesting that lineage-specific chromatin is established within the subtending ducts during puberty. An integrative analysis of five stages spanning the pregnancy cycle revealed distinct stage-specific profiles and the presence of cycling basal, mixed-lineage, and 'late' alveolar intermediates in pregnancy. Moreover, a number of intermediates were uncovered along the basal-luminal progenitor cell axis, suggesting a continuum of alveolar-restricted progenitor states. Conclusions This extended single cell transcriptome atlas of mouse mammary epithelial cells provides the most complete coverage for mammary epithelial cells during morphogenesis to date. Together with chromatin accessibility analysis of TEB structures, it represents a valuable framework for understanding developmental decisions within the mouse mammary gland.

Download Full-text

Domain-Directed Polymerase Chain Reaction Capable of Distinguishing Bacterial from Host DNA at the Single-Cell Level: Characterization of a Systematic Method to Investigate Putative Bacterial Infection in Idiopathic Disease

Analytical Biochemistry ◽

10.1006/abio.1996.9896 ◽

1997 ◽

Vol 244 (2) ◽

pp. 328-339 ◽

Cited By ~ 21

Author(s):

C.R. Steinman ◽

B. Muralidhar ◽

G.J. Nuovo ◽

P.M. Rumore ◽

D. Yu ◽

...

Keyword(s):

Polymerase Chain Reaction ◽

Bacterial Infection ◽

Single Cell ◽

Single Cell Level ◽

Cell Level ◽

Chain Reaction ◽

Systematic Method ◽

Polymerase Chain ◽

Idiopathic Disease

Download Full-text

Single-cell analysis of somatic mutation burden in mammary epithelial cells of pathogenic BRCA1/2 mutation carriers

Journal of Clinical Investigation ◽

10.1172/jci148113 ◽

2022 ◽

Author(s):

Shixiang Sun ◽

Kristina Brazhnik ◽

Moonsook Lee ◽

Alexander Y. Maslov ◽

Yi Zhang ◽

...

Keyword(s):

Epithelial Cells ◽

Single Cell ◽

Somatic Mutation ◽

Single Cell Analysis ◽

Mammary Epithelial Cells ◽

Mammary Epithelial ◽

Cell Analysis ◽

Mutation Carriers ◽

Mutation Burden

Download Full-text

Single Cell RNA Sequencing of Human Milk-Derived Cells Reveals Sub-Populations of Mammary Epithelial Cells with Molecular Signatures of Progenitor and Mature States: a Novel, Non-invasive Framework for Investigating Human Lactation Physiology

Journal of Mammary Gland Biology and Neoplasia ◽

10.1007/s10911-020-09466-z ◽

2020 ◽

Author(s):

Jayne F. Martin Carli ◽

G. Devon Trahan ◽

Kenneth L. Jones ◽

Nicole Hirsch ◽

Kristy P. Rolloff ◽

...

Keyword(s):

Epithelial Cells ◽

Human Milk ◽

Single Cell ◽

Rna Sequencing ◽

Mammary Epithelial Cells ◽

Mammary Epithelial ◽

Molecular Signatures ◽

Human Lactation ◽

Non Invasive ◽

Single Cell Rna Sequencing

Download Full-text

Isolation and characterization of individual functionally reactive cytotoxic T lymphocytes: conjugation, killing and recycling at the single cell level

European Journal of Immunology ◽

10.1002/eji.1830051205 ◽

1975 ◽

Vol 5 (12) ◽

pp. 818-822 ◽

Cited By ~ 130

Author(s):

D. Zagury ◽

Jacky Bernard ◽

Noelle Thierness ◽

M. Feldman ◽

G. Berke

Keyword(s):

T Lymphocytes ◽

Single Cell ◽

Cytotoxic T Lymphocytes ◽

Single Cell Level ◽

Cell Level ◽

Isolation And Characterization

Download Full-text

Characterization of the development of the mouse cochlear epithelium at the single cell level

Nature Communications ◽

10.1038/s41467-020-16113-y ◽

2020 ◽

Vol 11 (1) ◽

Cited By ~ 14

Author(s):

Likhitha Kolla ◽

Michael C. Kelly ◽

Zoe F. Mann ◽

Alejandro Anaya-Rocha ◽

Kathryn Ellis ◽

...

Keyword(s):

Single Cell ◽

Single Cell Level ◽

Cell Level

Download Full-text

Identification and characterization of CCAAT/Enhancer Binding proteindelta (C/EBPdelta) target genes in G0 growth arrested mammary epithelial cells

BMC Molecular Biology ◽

10.1186/1471-2199-9-83 ◽

2008 ◽

Vol 9 (1) ◽

pp. 83 ◽

Cited By ~ 11

Author(s):

Yingjie Zhang ◽

Tong Liu ◽

Pearlly Yan ◽

Tim Huang ◽

Jim DeWille

Keyword(s):

Epithelial Cells ◽

Target Genes ◽

Mammary Epithelial Cells ◽

Mammary Epithelial ◽

Identification And Characterization

Download Full-text

Cross-Tissue Characterization of Heterogeneities of Mesenchymal Stem Cells and Their Differentiation Potentials

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.781021 ◽

2021 ◽

Vol 9 ◽

Author(s):

Wenhong Hou ◽

Li Duan ◽

Changyuan Huang ◽

Xingfu Li ◽

Xiao Xu ◽

...

Keyword(s):

Single Cell ◽

Umbilical Cord ◽

Stromal Cells ◽

Tissue Characterization ◽

Single Cell Level ◽

Rna Seq ◽

Cell Level ◽

Cell Sources ◽

Cell Subpopulations

Mesenchymal stem/stromal cells (MSCs) are promising cell sources for regenerative medicine and the treatment of autoimmune disorders. Comparing MSCs from different tissues at the single-cell level is fundamental for optimizing clinical applications. Here we analyzed single-cell RNA-seq data of MSCs from four tissues, namely umbilical cord, bone marrow, synovial tissue, and adipose tissue. We identified three major cell subpopulations, namely osteo-MSCs, chondro-MSCs, and adipo/myo-MSCs, across all MSC samples. MSCs from the umbilical cord exhibited the highest immunosuppression, potentially indicating it is the best immune modulator for autoimmune diseases. MSC subpopulations, with different subtypes and tissue sources, showed pronounced differences in differentiation potentials. After we compared the cell subpopulations and cell status pre-and-post chondrogenesis induction, osteogenesis induction, and adipogenesis induction, respectively, we found MSC subpopulations expanded and differentiated when their subtypes consist with induction directions, while the other subpopulations shrank. We identified the genes and transcription factors underlying each induction at the single-cell level and subpopulation level, providing better targets for improving induction efficiency.

Download Full-text