Junhong Choi
@choijunhong.bsky.social
PI at MSKCC. Synthetic (Developmental) Biology + Molecular Recording + Genomics Tech Dev. Words like physicality of information make my heart go a little faster.
We’re still thinking about what this means for actual embryonic development, but it’s exciting to observe such effects in a tractable stem-cell-derived model! Huge thanks to everyone in the @jshendure.bsky.social lab—especially Jay—for supporting this project from start to finish! (13/13)
May 27, 2025 at 2:57 PM
We’re still thinking about what this means for actual embryonic development, but it’s exciting to observe such effects in a tractable stem-cell-derived model! Huge thanks to everyone in the @jshendure.bsky.social lab—especially Jay—for supporting this project from start to finish! (13/13)
This reminds us of “transiently heritable” traits seen in other contexts, such as cellular reprogramming (doi.org/10.1038/s415...) and drug resistance in cancer (doi.org/10.1016/j.ce... the clonal bias can shape their fate decisions and cellular phenotypes. (12/13)
Single-cell mapping of lineage and identity in direct reprogramming - Nature
Combinatorial tagging of single cells using expressed DNA barcodes, delivered by a lentiviral vector, is used to track individual cells and reconstruct their lineages and trajectories during cell fate...
doi.org
May 27, 2025 at 2:57 PM
This reminds us of “transiently heritable” traits seen in other contexts, such as cellular reprogramming (doi.org/10.1038/s415...) and drug resistance in cancer (doi.org/10.1016/j.ce... the clonal bias can shape their fate decisions and cellular phenotypes. (12/13)
Even after resetting spatial context, we saw persistent clonal biases—suggesting an intrinsic, heritable factor shaping fate decisions, independent of spatial cues like Wnt signaling. (11/13)
May 27, 2025 at 2:57 PM
Even after resetting spatial context, we saw persistent clonal biases—suggesting an intrinsic, heritable factor shaping fate decisions, independent of spatial cues like Wnt signaling. (11/13)
In this “tree-of-trees” experiment, we dissociated a monoclonal colony into single cells (resetting spatial context) and used them to generate separate gastruloids. (10/13)
May 27, 2025 at 2:57 PM
In this “tree-of-trees” experiment, we dissociated a monoclonal colony into single cells (resetting spatial context) and used them to generate separate gastruloids. (10/13)
Previous works (e.g., by Michelle doi.org/10.1016/j.de... and by Harry doi.org/10.1038/s415...) suggested spatial context plays a big role in gastruloids fate decisions. So we designed a two-epoch experiment to test that… (9/13)
Recording morphogen signals reveals mechanisms underlying gastruloid symmetry breaking - Nature Cell Biology
Toettcher, McNamara and colleagues use synthetic ‘signal-recording’ gene circuits on mouse gastruloids and find that cell sorting rearranges patchy domains of Wnt activity into a single pole, which de...
doi.org
May 27, 2025 at 2:57 PM
Previous works (e.g., by Michelle doi.org/10.1016/j.de... and by Harry doi.org/10.1038/s415...) suggested spatial context plays a big role in gastruloids fate decisions. So we designed a two-epoch experiment to test that… (9/13)
Together, we found: Cell fates can diverge as early as the first cell division! Sister cells can follow drastically different paths—e.g., one lineage becomes mostly somites, another mostly neurons! (8/13)
May 27, 2025 at 2:57 PM
Together, we found: Cell fates can diverge as early as the first cell division! Sister cells can follow drastically different paths—e.g., one lineage becomes mostly somites, another mostly neurons! (8/13)
Once we knew monoclonal lineage recording worked, we teamed up with @cxqiu.bsky.social—an amazing and generous computational biologist—to dive into the lineage trees. (7/13)
May 27, 2025 at 2:57 PM
Once we knew monoclonal lineage recording worked, we teamed up with @cxqiu.bsky.social—an amazing and generous computational biologist—to dive into the lineage trees. (7/13)
(Side note: Sam also used this approach to generate monoclonal embryoid bodies for perturbation screening with @sdomcke.bsky.social and @cxqiu.bsky.social.) bsky.app/profile/sdom... (6/13)
Expanding Perturb-seq-like screens to multicellular systems also increases the complexity of confounding effects. We encountered this when we perturbed all TFs in mosaic embryoid bodies (EBs) and develop a scalable solution by barcoding monoclonal individuals. 🧵 www.biorxiv.org/content/10.1...
Barcoded monoclonal embryoids are a potential solution to confounding bottlenecks in mosaic organoid screens
Genetic screens in organoids hold tremendous promise for accelerating discoveries at the intersection of genomics and developmental biology. Embryoid bodies (EBs) are self-organizing multicellular str...
www.biorxiv.org
May 27, 2025 at 2:57 PM
(Side note: Sam also used this approach to generate monoclonal embryoid bodies for perturbation screening with @sdomcke.bsky.social and @cxqiu.bsky.social.) bsky.app/profile/sdom... (6/13)
To solve this, Sam developed a robust protocol to create “monoclonal gastruloids”—gastruloids seeded from a single cell. These were ideal for DNA Typewriter lineage reconstruction! (5/13)
May 27, 2025 at 2:57 PM
To solve this, Sam developed a robust protocol to create “monoclonal gastruloids”—gastruloids seeded from a single cell. These were ideal for DNA Typewriter lineage reconstruction! (5/13)
However, conventional gastruloids start with 300–500 cells, and that’s a problem for us—lineage tracing from 500 cells gives you 500 independent trees, masking clonal info from earlier developmental events. (4/13)
May 27, 2025 at 2:57 PM
However, conventional gastruloids start with 300–500 cells, and that’s a problem for us—lineage tracing from 500 cells gives you 500 independent trees, masking clonal info from earlier developmental events. (4/13)
Mouse 3D gastruloids seemed like the perfect testbed—they mimic key features of early mammalian development in both shape and cell types. (Image from Turner @gastruloids.bsky.social & Martinez Arias @amartinezarias.bsky.social : doi.org/10.1002/bies...) (3/13)
May 27, 2025 at 2:57 PM
Mouse 3D gastruloids seemed like the perfect testbed—they mimic key features of early mammalian development in both shape and cell types. (Image from Turner @gastruloids.bsky.social & Martinez Arias @amartinezarias.bsky.social : doi.org/10.1002/bies...) (3/13)
We previously showed that DNA Typewriter can record high-resolution lineage trees in cultured cells (HEK293T). www.nature.com/articles/s41... But could we use it to study how clonal memory shapes cell fate decisions during development? (2/13)
A time-resolved, multi-symbol molecular recorder via sequential genome editing - Nature
A DNA memory device, DNA Typewriter, uses sequential prime editing to record the order of multiple cellular events.
www.nature.com
May 27, 2025 at 2:57 PM
We previously showed that DNA Typewriter can record high-resolution lineage trees in cultured cells (HEK293T). www.nature.com/articles/s41... But could we use it to study how clonal memory shapes cell fate decisions during development? (2/13)
Thank you for kind words!!
May 7, 2025 at 12:41 PM
Thank you for kind words!!
We are very thankful to Jay Shendure @jshendure.bsky.social and the lab for fostering our views that led to this review, @cp-trendsgenetics.bsky.social for all their help, and the funding agencies (NHGRI, NCI, and @damonrunyon.org) that made this work (and our previous works) possible! (2/2)
May 6, 2025 at 2:39 PM
We are very thankful to Jay Shendure @jshendure.bsky.social and the lab for fostering our views that led to this review, @cp-trendsgenetics.bsky.social for all their help, and the funding agencies (NHGRI, NCI, and @damonrunyon.org) that made this work (and our previous works) possible! (2/2)