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. 2021 Jun 3;9:668851. doi: 10.3389/fcell.2021.668851

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Copyright © 2021 Mohan, Raj Rajan, Mohan, Kollenchery Puthenveettil and Maliekal.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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The heterogeneity in cancer stem cells (CSCs). The different populations identified in breast CSCs and their markers are represented. The non-dividing Quiescent population, Progenitor population, Progenitor-like population, and the differentiated non-CSC population express a gradient of pluripotent, mesenchymal/epithelial and proliferative markers. The Quiescent population expresses a high level of pluripotent transcriptional factors and a moderate level of mesenchymal markers. With differentiation, the level of pluripotent markers comes down. The Progenitor population starts to express proliferative markers, CD44 and epithelial markers in very low levels. The Progenitor-like population co-expresses mesenchymal and epithelial markers manifesting a gradual increase in hybrid-epithelial-mesenchymal transition (EMT) phenotype. This population also expresses CSC markers ALDH1A1/A3 and ABCG2 contributing to drug-resistance. Non-CSCs lose the expression of pluripotent and other CSC markers except for CD44. The proliferative markers, epithelial markers, and mesenchymal markers are at maximum expression level in this population. This population can metastasize, but cannot initiate tumor until they dedifferentiate into CSCs.