@dmichelson.bsky.social
MD/PhD student at Harvard/MIT, fascinated by immune tolerance and autoimmunity
Beautiful work by @mmr2.bsky.social unlocking a new layer of immune regulation in the CNS โ check it out!
29.01.2025 14:11 โ ๐ 5 ๐ 1 ๐ฌ 1 ๐ 0Super super cool work! Do you have a sense of what the chemical compositions of these long lived lesions might be?
16.01.2025 00:06 โ ๐ 1 ๐ 0 ๐ฌ 1 ๐ 0It 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!
27.12.2024 16:30 โ ๐ 2 ๐ 0 ๐ฌ 1 ๐ 0We 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 weโve only scratched the surface of central tolerance in human health and disease.
27.12.2024 16:30 โ ๐ 0 ๐ 0 ๐ฌ 1 ๐ 0
Whole-mount imaging of a zebrafish with thymus fluorescently labeled by lck-GFP and muscle fluorescently labeled by mylpfa-mCherry
Phylogenetic tree showing evolutionary divergence among lampreys, zebrafish, mice and humans
UMAP plot showing zebrafish mimetic cells including muscle, tuft cells, ionocytes, hair cells, neuroendocrine cells, ciliated cells and assorted other subtypes
W/ Sara Rubin & Wilson Gomarga in Len Zonโs 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.
27.12.2024 16:30 โ ๐ 0 ๐ 0 ๐ฌ 1 ๐ 0
Heatmap showing marker genes of various human mimetic cells
Dotplot showing lineage-defining transcription factors expressed in various human mimetic cells
We defined new human mimetic cells, including ones mirroring kidney ฮฒ-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.
27.12.2024 16:30 โ ๐ 1 ๐ 0 ๐ฌ 1 ๐ 0
UMAP plot with clusters of mimetic cells including ionocytes, muscle, keratinocytes, various neuroendocrine cells, cochlear hair cells and tuft cells as well as Aire-stage, immature, cycling and transitional mTECs
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.
27.12.2024 16:30 โ ๐ 1 ๐ 0 ๐ฌ 1 ๐ 0
Flow cytometry plots showing gating of human mimetic cells
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.
27.12.2024 16:30 โ ๐ 1 ๐ 0 ๐ฌ 1 ๐ 0Most 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.
27.12.2024 16:30 โ ๐ 1 ๐ 0 ๐ฌ 1 ๐ 0
We previously discovered that thymic epithelial cells can mimic diverse cell types from throughout the body. These โmimetic cellsโ preview our tissues to T cells, teach self/non-self discrimination, and prevent autoimmunity.
www.cell.com/cell/fulltex...
www.annualreviews.org/content/jour...
Excited to share our latest work on the thymus, out @cp-immunity.bsky.social! We define thymic mimetic cells in humans and show they are an evolutionarily ancient part of adaptive immunity. Terrific collab w Cardiac Surgery @bostonchildrens.bsky.social and Len Zon's lab
www.cell.com/immunity/abs...
Testing.. is this thing on? Hi @bsky.app !
19.12.2024 03:31 โ ๐ 4 ๐ 0 ๐ฌ 0 ๐ 0
