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Transcriptomic Analysis of Breast Cancer Stem Cells and Development of a pALDH1A1:mNeptune Reporter System for Live Tracking
Author(s) -
Bidan Nadège,
BailleulDubois Justine,
Duval Jérémy,
Winter Marie,
Denoulet Marie,
Hannebicque Karine,
ElSayed Ihsan Y.,
Ginestier Christophe,
Forissier Violaine,
CharafeJauffret Emmanuelle,
Macario Ma,
Matsunaga Yukiko T,
Meignan Samuel,
Anquez François,
Julien Sylvain,
Bonnefond Amélie,
Derhourhi Mehdi,
Le Bourhis Xuefen,
Lagadec Chann
Publication year - 2019
Publication title -
proteomics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.26
H-Index - 167
eISSN - 1615-9861
pISSN - 1615-9853
DOI - 10.1002/pmic.201800454
Subject(s) - transcriptome , breast cancer , tracking (education) , stem cell , biology , computational biology , cancer stem cell , cancer research , cancer , microbiology and biotechnology , gene , genetics , gene expression , psychology , pedagogy
Many solid cancers are hierarchically organized with a small number of cancer stem cells (CSCs) able to regrow a tumor, while their progeny lacks this feature. Breast CSC is known to contribute to therapy resistance. The study of those cells is usually based on their cell‐surface markers like CD44 high /CD24 low/neg or their aldehyde dehydrogenase (ALDH) activity. However, these markers cannot be used to track the dynamics of CSC. Here, a transcriptomic analysis is performed to identify segregating gene expression in CSCs and non‐CSCs, sorted by Aldefluor assay. It is observed that among ALDH‐associated genes, only ALDH1A1 isoform is increased in CSCs. A CSC reporter system is then developed by using a far red‐fluorescent protein (mNeptune) under the control of ALDH1A1 promoter. mNeptune‐positive cells exhibit higher sphere‐forming capacity, tumor formation, and increased resistance to anticancer therapies. These results indicate that the reporter identifies cells with stemness characteristics. Moreover, live tracking of cells in a microfluidic system reveals a higher extravasation potential of CSCs. Live tracking of non‐CSCs under irradiation treatment show, for the first time, live reprogramming of non‐CSCs into CSCs. Therefore, the reporter will allow for cell tracking to better understand the implication of CSCs in breast cancer development and recurrence.