Thrilled to share our new paper in @CellStemCell, where we turn programmed cell death into a tool for building better tissues. (1/8): cell.com/cell-stem-cell/full…
Mohammad Taheri retweeted
1/10 What if building tissues requires not only adding the right cells, materials or ECMs, but removing the wrong ones too? (free link at 10/10)
#Development builds through both construction and elimination. Yet tissue engineering largely focuses on addition. We do not have a #subtractive framework in our synthetic in. whereas tissues operate far from the constraints exist in vivo.
Our new @CellStemCell paper explores the missing half: "Subtractive Tissue Engineering" is how we named it. #development #celldeath #syntheticbiology #systemsbiology #embryogenesis #organoids #NAMs #human #stemcells🧵
ALT Programmable subtraction for tissue engineering
Thanks to @MoEbrahimkhani and @samira_kiani1 for their guidance and mentorship, @xiang_1905 for three years of relentless work on this, @MokhtariTahere for her instrumental help with constructing the genetic circuits, and the rest of our coauthors. (8/8)
In embryoids, apoptosis restricted to cells occupying the prospective lumen enhanced cavitation. (7/8)
In liver organoids, clearing away immature hepatocyte-like cells enhanced maturity, while a microRNA gate protected endothelium and preserved the vascular network. (6/8)
SynBITE senses cell state through promoter activity or microRNA signatures, processes those inputs through logic gates, and triggers apoptosis in the populations that don’t match. All of this happens as morphogenesis takes place. (5/8)
Building this required an actuator tailored to function in stem cell derived systems. We made an enhanced version of iCasp9 with low background activity and a broad dynamic range, where killing requires two small molecules instead of one. (4/8)
We address this with subtractive multicellular engineering: clearing away aberrant cells during the morphogenesis of multicellular systems. Our platform, SynBITE, does this with genetic circuits that integrate logic computation and regulated apoptosis. (3/8)
Multicellular organisms prune aberrant cells during development via apoptosis, sculpting structures and refining composition as tissues form. Engineered equivalents are absent from how we build organoids and embryoids, so abberant cells persist. (2/8)
Mohammad Taheri retweeted
it's a pleasure to share our lab preprint on “Modelling Human Post-Implantation Development via
Extra-Embryonic Niche Engineering” ! It is timely considering recent works reported from labs of @MZG_Lab @jacob_hanna @ISSCR #ISSCR2023. See below. I hope you will enjoy the work!
Mohammad Taheri retweeted
It is my pleasure to present the preprint for my graduate research in the @MoEbrahimkhani lab until this point, out now in biorxiv, modelling the human bilaminar disc through gastrulation and beyond!
biorxiv.org/content/10.1101/…
