Breast cancer arises from breast epithelial cells that acquire genetic alterations leading to subsequent loss of tissue homeostasis. Several distinct epithelial subpopulations have been proposed, but complete understanding of the spectrum of heterogeneity and differentiation hierarchy in the human breast remains elusive. Here, we used single-cell mRNA sequencing (scRNAseq) to profile the transcriptomes of 25,790 primary human breast epithelial cells isolated from reduction mammoplasties of seven individuals. Unbiased clustering analysis reveals the existence of three distinct epithelial cell populations, one basal and two luminal cell types, which we identify as secretory L1- and hormone-responsive L2-type cells. Pseudotemporal reconstruction of differentiation trajectories produc one continuous lineage hierarchy that closely connects the basal lineage to the two differentiated luminal branches. Our comprehensive cell atlas provides novel insights into cellular blueprint of the human breast epithelium and will form the foundation to understand how the system goes awry during breast cancer. Overall design: Microfluidics-enabled Single Cell RNA sequencing libraries were generated for 3 adult human women using the Fluidigm C1 and sequenced on the Illumina HighSeq 2500
Single-cell landscape in mammary epithelium reveals bipotent-like cells associated with breast cancer risk and outcome.
Sex, Specimen part, Subject
View SamplesBreast cancer arises from breast epithelial cells that acquire genetic alterations leading to subsequent loss of tissue homeostasis. Several distinct epithelial subpopulations have been proposed, but complete understanding of the spectrum of heterogeneity and differentiation hierarchy in the human breast remains elusive. Here, we used single-cell mRNA sequencing (scRNAseq) to profile the transcriptomes of 25,790 primary human breast epithelial cells isolated from reduction mammoplasties of seven individuals. Unbiased clustering analysis reveals the existence of three distinct epithelial cell populations, one basal and two luminal cell types, which we identify as secretory L1- and hormone-responsive L2-type cells. Pseudotemporal reconstruction of differentiation trajectories produc one continuous lineage hierarchy that closely connects the basal lineage to the two differentiated luminal branches. Our comprehensive cell atlas provides novel insights into cellular blueprint of the human breast epithelium and will form the foundation to understand how the system goes awry during breast cancer. Overall design: Microfluidics-enabled Single Cell RNA sequencing libraries were generated for 3 adult human women using the Fluidigm C1 and sequenced on the Illumina HighSeq 2500
Single-cell landscape in mammary epithelium reveals bipotent-like cells associated with breast cancer risk and outcome.
Sex, Specimen part, Subject
View SamplesBreast cancer arises from breast epithelial cells that acquire genetic alterations leading to subsequent loss of tissue homeostasis. Several distinct epithelial subpopulations have been proposed, but complete understanding of the spectrum of heterogeneity and differentiation hierarchy in the human breast remains elusive. Here, we used single-cell mRNA sequencing (scRNAseq) to profile the transcriptomes of 25,790 primary human breast epithelial cells isolated from reduction mammoplasties of seven individuals. Unbiased clustering analysis reveals the existence of three distinct epithelial cell populations, one basal and two luminal cell types, which we identify as secretory L1- and hormone-responsive L2-type cells. Pseudotemporal reconstruction of differentiation trajectories produc one continuous lineage hierarchy that closely connects the basal lineage to the two differentiated luminal branches. Our comprehensive cell atlas provides novel insights into cellular blueprint of the human breast epithelium and will form the foundation to understand how the system goes awry during breast cancer. Overall design: Microfluidics-enabled Single Cell RNA sequencing libraries were generated for 3 adult human women using the Fluidigm C1 and sequenced on the Illumina HighSeq 2500
Single-cell landscape in mammary epithelium reveals bipotent-like cells associated with breast cancer risk and outcome.
No sample metadata fields
View SamplesTo discover novel growth factors for hematopoietic stem- and progenitor cells (HSPCs), we have assessed cytokine responses of cord blood (CB)-derived CD34+ cells in a high-content growth factor screen. We identify the immunoregulatory chemokine (C-C motif) ligand 28 (CCL28) as a novel growth factor that directly stimulates proliferation of primitive hematopoietic cells from different ontogenetic origins.
Identification of the chemokine CCL28 as a growth and survival factor for human hematopoietic stem and progenitor cells.
Specimen part
View SamplesResidence of cancer-propagating cells (CPCs) within preferential microenvironmental niches has a major part in evading therapy. However, the nature of niches involved and the mechanisms protecting CPCs remain largely unknown. We addressed these issues in mouse transplantation models of acute lymphoblastic leukemia (ALL). When the engrafted leukemic cells substantially damaged adjacent vascular structures and endosteal linings in the bone marrow (BM), after chemotherapy small foci of CPCs were retained, surrounded by sheaths of supporting cells that comprise a novel niche. We investigated patients BM biopsies and found evidence of a similar process in patients receiving induction-therapy. The efficacy of chemotherapy was enhanced by interfering with the niche formation or niche-CPC interaction. We therefore identified a therapy-induced niche that protects CPCs.
Leukemia propagating cells rebuild an evolving niche in response to therapy.
Specimen part, Treatment
View SamplesProspective isolation is critical to understand the cellular and molecular aspects of stem cell heterogeneity. Here we identify the cell surface antigen CD9 as a novel positive marker that provides a simple alternative for hematopoietic stem cell-isolation at high purity Overall design: mRNA profiles of LT and ST HSCs
The tetraspanin CD9 affords high-purity capture of all murine hematopoietic stem cells.
Subject
View SamplesLineage negativ Sca1+ Kit+ bone marrow cells (containing putative hematopoietic stem cells) subfractionation based on CD34 and FLT3 identifies three functionally destinc subpopulations (LSKCD34-FLT3-, LSKCD34+FLT3- & LSKCD34+FLT3+).
Molecular evidence for hierarchical transcriptional lineage priming in fetal and adult stem cells and multipotent progenitors.
No sample metadata fields
View SamplesDuring development a specialised subset of endothelial cells, the haemogenic endothelium, undergo an endothelial-to-haematopoietic transition. This process critically involves the transcription factor Runx1. Here we have isolated a specific subpopulation of endothelial cells using a Runx1 enhancer-reporter transgenic mouse line (23GFP). We have compared the gene expression profile of this population to non-23GFP expressing endothelial cells and CD41 expressing haematopoietic progenitor cells to assess whether 23GFP expression marks a biologically distinct subset of endothelium.
Early dynamic fate changes in haemogenic endothelium characterized at the single-cell level.
Specimen part
View SamplesTumor relapse is associated with dismal prognosis, but responsible biological principles remain incompletely understood. To isolate and characterize relapse-inducing cells, we used genetic engineering and proliferation-sensitive dyes in patient-derived xenografts of acute lymphoblastic leukemia (ALL). We identified a rare subpopulation that resembled relapse-inducing cells with combined properties of long-term dormancy, treatment resistance, and stemness. Single-cell and bulk expression profiling revealed their similarity to primary ALL cells isolated from pediatric and adult patients at minimal residual disease (MRD). Therapeutically adverse characteristics were reversible, as resistant, dormant cells became sensitive to treatment and started proliferating when dissociated from the in vivo environment. Our data suggest that ALL patients might profit from therapeutic strategies that release MRD cells from the niche. Overall design: Gene expression profiles from two PDX ALL Samples (ALL-199 & ALL-265) were generated for either dormant (LRC) vs. dividing (non-LRC) cells or drug treated vs. non-treated cells. For single cell analysis one mouse were analyzed for each condition.
Characterization of Rare, Dormant, and Therapy-Resistant Cells in Acute Lymphoblastic Leukemia.
Specimen part, Treatment, Subject
View SamplesGene expression analysis of early thymic progenitors and thymus seeding progenitors
The earliest thymic T cell progenitors sustain B cell and myeloid lineage potential.
Sex, Age, Specimen part, Disease
View Samples