Figure 2.

The hierarchy in CSCs. Our analysis on the available literature on single-cell analyses conducted in breast cancer has revealed that the expression of pluripotency markers without CD44 marks the Quiescent CSC, while CD44 along with moderate expression of pluripotency markers define the Progenitor CSC population. These cells gradually lose the expression of pluripotency markers and gain the expression of ABCG2 and ALDH1A1 to get converted to Progenitor-like CSC population. According to the niche factors, these cells can be converted to the drug-resistant-CSCs or metastasis initiating cells (MICs). When this Progenitor-like CSC population loses all the CSC markers except CD44, they are converted to the Proliferating non-CSCs. The Quiescent cells, Progenitor cells, and Progenitor-like cells are considered as CSCs or tumor-initiating cells (TICs), which exhibit tumor initiation potential. The Progenitor like population having hybrid EMT phenotype might be the drug-resistant CSCs and MICs. The proliferating population with hybrid EMT might be highly metastatic, and they can remain dormant at distant sites. These cells are the seeds of recurrence at a different site. They might initiate tumor if they acquire stemness depending on the metastatic niche.