Figures & data
Figure 1. Putative differentiation lineage hierarchy of normal human breast. Stem cells are mostly quiescent and they rarely proliferate, but they give rise to a rapidly proliferating finite lifespan progenitor cells with multi-lineage differentiation potential. The more differentiated cell types increasingly become mitotically less active, and finally the terminally differentiated cells become post-mitotic. Among the normal breast cell types, only K18[+] cells were highly proliferative, which makes them the best candidate for the transit amplifying cells. We attempted to organize the rest of the breast cell types in a way where each differentiation step involves gain or loss of a single marker. Based on this constraint, we postulate that transit amplifying cell first loses its proliferative capacity which coincides with VDR upregulation giving rise to an oligo-potential progenitor (L6). This cell either maintains K18 expression and gains ER and AR expression, giving rise to luminal HR+ cell types (L4-5 and L9-11), or it down-regulates K18 and up-regulates K5 (L7). When this cell down-regulates VDR (L3) and up-regulates SMA and p63, it generates the typical K5[+], HR– and K18– myoeptihelial cell type (M2). As this cell down-regulates K5, it generates the second subpopulation of K5– myoepithelial cells (M1).The above model depicts one possible scenario among many. Describing the interrelatedness of the breast cell types we identified and understanding their differentiation lineage hierarchy will require in vivo and functional ex vivo experiments that are not currently possible for technical reasons.
![Figure 1. Putative differentiation lineage hierarchy of normal human breast. Stem cells are mostly quiescent and they rarely proliferate, but they give rise to a rapidly proliferating finite lifespan progenitor cells with multi-lineage differentiation potential. The more differentiated cell types increasingly become mitotically less active, and finally the terminally differentiated cells become post-mitotic. Among the normal breast cell types, only K18[+] cells were highly proliferative, which makes them the best candidate for the transit amplifying cells. We attempted to organize the rest of the breast cell types in a way where each differentiation step involves gain or loss of a single marker. Based on this constraint, we postulate that transit amplifying cell first loses its proliferative capacity which coincides with VDR upregulation giving rise to an oligo-potential progenitor (L6). This cell either maintains K18 expression and gains ER and AR expression, giving rise to luminal HR+ cell types (L4-5 and L9-11), or it down-regulates K18 and up-regulates K5 (L7). When this cell down-regulates VDR (L3) and up-regulates SMA and p63, it generates the typical K5[+], HR– and K18– myoeptihelial cell type (M2). As this cell down-regulates K5, it generates the second subpopulation of K5– myoepithelial cells (M1).The above model depicts one possible scenario among many. Describing the interrelatedness of the breast cell types we identified and understanding their differentiation lineage hierarchy will require in vivo and functional ex vivo experiments that are not currently possible for technical reasons.](/cms/asset/854a390f-2450-4336-ab6b-7d2e6c6891a9/iery_a_956096_f0001_b.jpg)
Table 1. Normal human breast cell types.