Single-cell RNA-Seq reveals cell heterogeneity and hierarchy within mouse mammary epithelia
© 2018 Sun et al..
The mammary gland is very intricately and well organized into distinct tissues, including epithelia, endothelia, adipocytes, and stromal and immune cells. Many mammary gland diseases, such as breast cancer, arise from abnormalities in the mammary epithelium, which is mainly composed of two distinct lineages, the basal and luminal cells. Because of the limitation of traditional transcriptome analysis of bulk mammary cells, the hierarchy and heterogeneity of mammary cells within these two lineages remain unclear. To this end, using single-cell RNA-Seq coupled with FACS analysis and principal component analysis, we determined gene expression profiles of mammary epithelial cells of virgin and pregnant mice. These analyses revealed a much higher heterogeneity among the mammary cells than has been previously reported and enabled cell classification into distinct subgroups according to signature gene markers present in each group. We also identified and verified a rare CDH5+ cell subpopulation within a basal cell lineage as quiescent mammary stem cells (MaSCs). Moreover, using pseudo-temporal analysis, we reconstructed the developmental trajectory of mammary epithelia and uncovered distinct changes in gene expression and in biological functions of mammary cells along the developmental process. In conclusion, our work greatly refines the resolution of the cellular hierarchy in developing mammary tissues. The discovery of CDH5+ cells as MaSCs in these tissues may have implications for our understanding of the initiation, development, and pathogenesis of mammary tumors.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2018 |
|---|---|
| Erschienen: |
2018 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:293 |
|---|---|
| Enthalten in: |
The Journal of biological chemistry - 293(2018), 22 vom: 01. Juni, Seite 8315-8329 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Sun, Heng [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
Biomarker |
|---|
| Anmerkungen: |
Date Completed 16.01.2019 Date Revised 05.02.2021 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1074/jbc.RA118.002297 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM283144491 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM283144491 | ||
| 003 | DE-627 | ||
| 005 | 20231225035800.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2018 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1074/jbc.RA118.002297 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n0943.xml |
| 035 | |a (DE-627)NLM283144491 | ||
| 035 | |a (NLM)29666189 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Sun, Heng |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Single-cell RNA-Seq reveals cell heterogeneity and hierarchy within mouse mammary epithelia |
| 264 | 1 | |c 2018 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 16.01.2019 | ||
| 500 | |a Date Revised 05.02.2021 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2018 Sun et al. | ||
| 520 | |a The mammary gland is very intricately and well organized into distinct tissues, including epithelia, endothelia, adipocytes, and stromal and immune cells. Many mammary gland diseases, such as breast cancer, arise from abnormalities in the mammary epithelium, which is mainly composed of two distinct lineages, the basal and luminal cells. Because of the limitation of traditional transcriptome analysis of bulk mammary cells, the hierarchy and heterogeneity of mammary cells within these two lineages remain unclear. To this end, using single-cell RNA-Seq coupled with FACS analysis and principal component analysis, we determined gene expression profiles of mammary epithelial cells of virgin and pregnant mice. These analyses revealed a much higher heterogeneity among the mammary cells than has been previously reported and enabled cell classification into distinct subgroups according to signature gene markers present in each group. We also identified and verified a rare CDH5+ cell subpopulation within a basal cell lineage as quiescent mammary stem cells (MaSCs). Moreover, using pseudo-temporal analysis, we reconstructed the developmental trajectory of mammary epithelia and uncovered distinct changes in gene expression and in biological functions of mammary cells along the developmental process. In conclusion, our work greatly refines the resolution of the cellular hierarchy in developing mammary tissues. The discovery of CDH5+ cells as MaSCs in these tissues may have implications for our understanding of the initiation, development, and pathogenesis of mammary tumors | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a CDH5+ cell | |
| 650 | 4 | |a biomarker | |
| 650 | 4 | |a breast cancer | |
| 650 | 4 | |a cell differentiation | |
| 650 | 4 | |a development | |
| 650 | 4 | |a mammary gland | |
| 650 | 4 | |a mammary stem cells (MaSCs) | |
| 650 | 4 | |a single cell RNA-seq | |
| 650 | 4 | |a stem cells | |
| 650 | 7 | |a Biomarkers |2 NLM | |
| 700 | 1 | |a Miao, Zhengqiang |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Xin |e verfasserin |4 aut | |
| 700 | 1 | |a Chan, Un In |e verfasserin |4 aut | |
| 700 | 1 | |a Su, Sek Man |e verfasserin |4 aut | |
| 700 | 1 | |a Guo, Sen |e verfasserin |4 aut | |
| 700 | 1 | |a Wong, Chris Koon Ho |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Xiaoling |e verfasserin |4 aut | |
| 700 | 1 | |a Deng, Chu-Xia |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t The Journal of biological chemistry |d 1945 |g 293(2018), 22 vom: 01. Juni, Seite 8315-8329 |w (DE-627)NLM000004995 |x 1083-351X |7 nnns |
| 773 | 1 | 8 | |g volume:293 |g year:2018 |g number:22 |g day:01 |g month:06 |g pages:8315-8329 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1074/jbc.RA118.002297 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 293 |j 2018 |e 22 |b 01 |c 06 |h 8315-8329 | ||