# MEMOIR: Recording, and in situ readout of cell lineage and transcriptional history

> **NIH NIH R01** · CALIFORNIA INSTITUTE OF TECHNOLOGY · 2020 · $1,389,186

## Abstract

Abstract
How do the cell fates, lineages, and molecular histories of individual cells control the development and
physiological function of tissues? This problem is of central importance throughout biomedical science.
However, progress has long been limited by two seemingly intractable, and inter-related, challenges: First, we
still have no method to determine the tree of lineage relationships among cells in developing tissues within
their native spatial context. Second, we have no way to determine the sequence of extracellular signals and
intracellular molecular events experienced by each cell in the developing tissue as it differentiates. Time-lapse
imaging has been the principal go-to method to image biological processes in living systems. However, a large
number of systems in biology and medicine do not permit live cell imaging methods because they are
inaccessible or optically opaque, such as mouse brains and embryos. Thus, there is a crucial need to develop
powerful new methods that can achieve inference of lineage information and cellular event histories from static
end-point measurements. Here we propose to develop a platform that enables cells to record lineage and
dynamic gene expression histories in their own genomes, within complex developing tissues. This platform will
combine two recently developed tools: first, genome editing tools that can “record” lineage information or
cellular events into the genome, and second, a single molecule microscopy based in situ technology called
sequential multiplexed Fluorescence In situ Hybridization (seqFISH) that can read out the recorded information
in single cells without dissecting them out from tissues. We call this method MEMOIR (Memory through
Enhanced Mutagenesis with Optical In situ Readout). Akin to using sequence variation for phylogenetic tree
analysis, this method will allow us to reconstruct the lineage tree for a population of cells as well as the
signaling event history within those cells based on the hierarchy of mutations incorporated into the target
region. We have performed the proof-of-principle experiments in mouse embryonic stem cells (mESCs) and
will extend the work to mouse embryos. We envision that MEMOIR will allow us to map lineages and signaling
events directly in complex tissues such as the brain and track cells in metastatic tumors.

## Key facts

- **NIH application ID:** 9967121
- **Project number:** 5R01MH116508-04
- **Recipient organization:** CALIFORNIA INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** Long Cai
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $1,389,186
- **Award type:** 5
- **Project period:** 2017-09-20 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9967121

## Citation

> US National Institutes of Health, RePORTER application 9967121, MEMOIR: Recording, and in situ readout of cell lineage and transcriptional history (5R01MH116508-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9967121. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*