Seminars

PhD Graduate Seminar-Ellenore Koren
06/07/2021 13:00

Stem Cells: a Matter of Life and Death

Stem

cells ( play a pivotal role in fueling homeostasis and regeneration While

much focus has been given to self renewal and differentiation pathways regulating

SC fate, little is known regarding the specific mechanisms utilized for their

elimination During my Ph D I determined that the pro apoptotic protein ARTS

(a Septin 4 isoform) is highly expressed in cells comprising the intestinal SC (

niche and that its deletion protects cells from undergoing apoptosis As a result,

the Sept 4 /ARTS crypt displays heightened proliferation and, in culture, generates

massive cystic organoids due to enhanced Wnt/β catenin signaling Importantly, mice

deleted for Sept 4 /ARTS exhibit resistance against intestinal damage in a manner

dependent upon ISCs Finally, I was able to show that ARTS interacts with XIAP in

intestinal crypt cells and that deletion of XIAP can abrogate Sept 4 /ARTS

dependent phenotypes in an epistatic manner (Koren et al Nature Communications,

2018 These results indicate that ISCs utilize specific apoptotic proteins for their

elimination representing a unique therapeutic target

Currently

I am testing distinct compounds that have been identified via high

throughput in vitro and in silico screening platforms, for their potential to

therapeutically block the ARTS/ XIAP interface It is my greatest hope that my findings

may one day serve as a staple for human disease treatments

In

the skin, the presence of a distinct SC population that maintains the interfollicular

epidermis ( is highly debated We found that basal keratinocytes marked by Thy 1

do not express T cell markers, express a unique transcriptional profile, cycle

significantly slower than basal epidermal progenitors and display significant

expansion potential in vitro Multicolor lineage tracing analyses and mathematical

modeling reveals that Thy 1 basal keratinocytes do not compete neutrally alike IFE

progenitors and contribute long term to both epidermal replenishment and wound

repair Importantly, ablation of Thy 1 cells in T cell deficient mice strongly impairs

these processes, thus indicating the non redundant function of Thy 1 SCs in the

epidermis Taken together, these findings indicate the existence of a distinct slow

cycling SC population that plays a critical role in epidermal homeostasis and

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