Super super cool work! Do you have a sense of what the chemical compositions of these long lived lesions might be?

It takes a village to do human research, so many thanks to all those mentioned, as well as terrific co-first Brooke Huisman; our mentor Diane Mathis; Yuan Fang, Ian McGill, Katie Kohlsaat, Ji Myung Lee; Sasha Opotowsky for the initial spark, & the team @cp-immunity.bsky.social. All feedback welcome!

We hope that these data build a foundation for future studies of mimetic cells in humans and across the evolutionary tree. Mutations in AIRE of course cause APECED, but it feels like we’ve only scratched the surface of central tolerance in human health and disease.

W/ Sara Rubin & Wilson Gomarga in Len Zon’s lab, we also profiled thymi from zebrafish. Remarkably, zebrafish possess mimetic cells analogous to mammals despite >400M years of divergence. They also have fun fish-specific mimetics like gill ionocytes that regulate ion balance in aquatic life.

We defined new human mimetic cells, including ones mirroring kidney β-intercalated cells, cochlear hair cells, and DRG sensory neurons. We also discovered FEZF2+ neuroendocrine cells, which may mechanistically explain prior work from Takaba et al suggesting a role for Fezf2 in thymic tolerance.

Humans have an amazingly diverse mimetic cell repertoire with many similarities to mice. Interestingly, though, representation of certain mimetics varied widely between species: for instance, muscle mimetics expanded 25x in humans vs mice, whereas tuft mimetics contracted 25x.

With the help of wonderful collaborators @bostonchildrens.bsky.social (Meena Nathan, Pedro del Nido & team), we isolated mimetic cells from human thymi resected during cardiac corrective surgery and analyzed their composition/profiles using bulk and scRNA-seq.

Most of our prior work was in mice, but studies from Bautista et al and Park et al had suggested that humans possess mimetic cells, too. And as an MD/PhD, I wanted to know what was happening in people! So, we set out to comprehensively catalog human mimetic cells.

We previously discovered that thymic epithelial cells can mimic diverse cell types from throughout the body. These “mimetic cells” preview our tissues to T cells, teach self/non-self discrimination, and prevent autoimmunity.
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