Heterogeneity of Human Breast Stem and Progenitor Cells as Revealed by Transcriptional Profiling.
Heterogeneity of Human Breast Stem and Progenitor Cells as Revealed by Transcriptional Profiling.
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通过转录分析揭示了人乳房和祖细胞的异质性。
DOI：
10.1016/j.stemcr.2018.03.001
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发表时间：
2018-05-08
影响因子：
5.9
通讯作者：
Wicha MS
中科院分区：
文献类型：
--
作者：
Colacino JA;Azizi E;Brooks MD;Harouaka R;Fouladdel S;McDermott SP;Lee M;Hill D;Madden J;Boerner J;Cote ML;Sartor MA;Rozek LS;Wicha MS
在发育过程中，乳腺经历由干细胞驱动的广泛重塑。乳腺癌也是由以CD 44 + CD 24 low/−或醛脱氢酶（ALDH）表达为特征的癌症干细胞分层组织和驱动的。这些标志物鉴定了间充质和上皮细胞群，两者都能够引发肿瘤。对非癌性乳腺中的这些人群知之甚少。根据RNA测序，ALDH+和ALDH− CD 44 + CD 24 −人乳腺细胞分别具有上皮样和间充质样特征，流式细胞术显示一些细胞共表达ALDH+和CD 44 + CD 24 −。在单细胞水平，这些细胞具有最大的乳腺球形成能力，并表达高水平的干细胞和上皮-间充质转化相关基因，包括ID 1，SOX 2，TWIST 1和ZEB 2。我们进一步鉴定了单个ALDH+细胞，其具有表达与侵袭性三阴性乳腺癌相关的基因的混合上皮/间充质表型。这些结果突出了单细胞分析，以表征组织异质性，即使在标记富集的人群中，并确定定义这种异质性的基因和途径。ALDH+和CD 44 + CD 24 −乳腺细胞的分离和RNA-seq与癌症不同，ALDH+和CD 44 + CD 24 −群体中存在大量重叠ALDH+细胞的单细胞分析鉴定了意想不到的亚群结构混合上皮/间充质ALDH+细胞具有癌症样表达特征在这篇文章中，Colacino及其同事使用流式细胞术分选群体和单细胞分析来研究人类乳腺干细胞。他们在单细胞水平上发现了意想不到的表型和功能异质性，包括具有混合上皮/间充质表型和三阴性乳腺癌样基因表达模式的ALDH+干细胞亚群。
During development, the mammary gland undergoes extensive remodeling driven by stem cells. Breast cancers are also hierarchically organized and driven by cancer stem cells characterized by CD44+CD24low/− or aldehyde dehydrogenase (ALDH) expression. These markers identify mesenchymal and epithelial populations both capable of tumor initiation. Less is known about these populations in non-cancerous mammary glands. From RNA sequencing, ALDH+ and ALDH−CD44+CD24− human mammary cells have epithelial-like and mesenchymal-like characteristics, respectively, with some co-expressing ALDH+ and CD44+CD24− by flow cytometry. At the single-cell level, these cells have the greatest mammosphere-forming capacity and express high levels of stemness and epithelial-to-mesenchymal transition-associated genes including ID1, SOX2, TWIST1, and ZEB2. We further identify single ALDH+ cells with a hybrid epithelial/mesenchymal phenotype that express genes associated with aggressive triple-negative breast cancers. These results highlight single-cell analyses to characterize tissue heterogeneity, even in marker-enriched populations, and identify genes and pathways that define this heterogeneity. Isolation and RNA-seq of ALDH+ and CD44+CD24− breast cells Unlike in cancer, there is substantial overlap in ALDH+ and CD44+CD24− populations Single-cell analysis of ALDH+ cells identifies unexpected subpopulation structure Hybrid epithelial/mesenchymal ALDH+ cells have a cancer-like expression signature In this article, Colacino and colleagues use flow-cytometry-sorted populations and single-cell analyses to investigate human mammary stem cells. They discover unexpected phenotypic and functional heterogeneity at the single-cell level, including a subpopulation of ALDH+ stem cells with a hybrid epithelial/mesenchymal phenotype and triple-negative breast cancer-like gene expression pattern.
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影响因子：
10.5
作者：
Dontu, G;Abdallah, WM;Wicha, MS
通讯作者：
Wicha, MS
影响因子：
3.8
作者：
Kakarala, Madhuri;Brenner, Dean E.;Korkaya, Hasan;Cheng, Connie;Tazi, Karim;Ginestier, Christophe;Liu, Suling;Dontu, Gabriela;Wicha, Max S.
通讯作者：
Wicha, Max S.
影响因子：
23.9
作者：
Choudhury, Sibgat;Almendro, Vanessa;Polyak, Kornelia
通讯作者：
Polyak, Kornelia
影响因子：
5.9
作者：
Honeth, Gabriella;Schiavinotto, Tommaso;Dontu, Gabriela
通讯作者：
Dontu, Gabriela
DOI：
10.1186/bcr2590
发表时间：
2010
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Holm K;Hegardt C;Staaf J;Vallon-Christersson J;Jönsson G;Olsson H;Borg A;Ringnér M
通讯作者：
Ringnér M