Mass Cytometric Analysis Reveals Viable Activated Caspase-3+ Luminal Progenitors in the Normal Adult Human Mammary Gland
This week we profile a recent publication in Cell Reports from Dr. Connie Eaves (above, right),
David Knapp (below, first), Nagarajan Kannan (below, second), and Davide Pellacani (above, left) at the Terry Fox Laboratories.
Can you provide a brief overview of your lab’s current research focus?
The current research focus of the Eaves’ lab is to develop and deploy a variety of single cell analysis and in vitro and in vivo clonal tracking strategies to elucidate the diversity of molecular states of cells that maintain the integrity of normal human breast and blood forming tissues throughout development and aging, and to determine the first critical events that lead to their malignant transformation in defined prospectively analyzed de novo models.
What is the significance of the findings in this publication?
This publication makes two primary significant contributions to the field. The first is the development and description of a reproducible protocol for simultaneously quantifying the levels of 40 different surface and/or intracellular proteins on thousands to millions of individually assessed primary adherent human cells using mass cytometry. This will now make it possible for this technology to be applied to many other normal solid tissues or tumours which have previously not been accessible to this type of single-cell proteomic analysis. The second major finding is the discovery of a subset of luminal progenitors (LP) that show evidence of an activated apoptotic program that, at least in some cells can be reversed and enable the cells to recover extensive proliferative ability.
What are the next steps for this research?
Next steps for this research would be to determine how prevalent this reversible apoptotic process is among the entire normal human LP population and whether this is related to their acquisition of short telomeres and accumulated DNA damage and whether it might also be a feature of some malignant breast cancer cells and possibly linked to therapy resistance.
This research was funded by:
D.J.H.F.K. was supported by a Vanier Scholarship. N.K. was supported by CBCF-BC/Yukon and MITACS Elevate Postdoctoral Fellowships. Most of the antibodies used in this study were kindly provided by the Fluidigm Corporation. The study was supported by grants to C.J.E. from the Canadian Cancer SocietyResearch Institute.