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NIH grant 1DP2EB041714-01: Decoding Cell-Fate Decisions Through Molecular Recording
Institute: {'code': 'EB', 'abbreviation': 'NIBIB', 'name': 'National Institute of Biomedical Imaging and Bioengineering', 'admin_org_id': '12500035', 'admin_funding_url': ''}. PI: Junhong Choi. Award: $843125.
Start: 2026-09-30T00:00:00.
Project Summary
Deciphering how combinations of intrinsic and extrinsic cues determine cell fates is a
fundamental challenge in developmental biology, with broad implications for regenerative
medicine and cancer. While single-cell genomics technologies can profile cell states in detail,
current approaches cannot reconstruct how prior events—such as signaling pathway
activations, transient gene expression changes, or cell-cell interactions—shape developmental
outcomes. Here we propose to create a new class of single-cell genomic recording technologies
that integrate past cellular histories with present states captured by single-cell profiling. We will
design modular synthetic circuits that permanently encode diverse biological events—lineage
history, signaling activity, transient transcript expression, microenvironmental interactions, and
CRISPR-based genetic perturbations—as retrievable DNA edits. These records will enable the
retrospective reconstruction of developmental trajectories at single-cell resolution, revealing how
combinations of past cellular events program final cell type. As a proof of concept, we will apply
this system to the directed differentiation of human pluripotent stem cells into pancreatic islets, a
clinically relevant model for treating Type 1 diabetes. This approach will reveal how transient
cellular events affect cell-fate decisions and establish a broadly applicable platform for recording
and reconstructing sequences of cellular events that determine the final cell fate.document fetched 2026-10-15 02:48