# Tracking clonal dynamics during hematopoiesis: mechanistic insight via modeling and data analysis

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2021 · $185,418

## Abstract

PROJECT SUMMARY/ABSTRACT:
Understanding hematopoiesis, the formation and maintenance of blood and much of the adaptive immune
system is essential for understanding blood diseases and clinical approaches such as stem cell/gene therapy
and bone marrow transplantation. A long term goal is to disentangle and quantify the dynamics of how an
hematopoietic stem cell (HSC) generates the myriad of different cell lineages in blood. Specifically, we wish to
evaluate experimental observations and data to deduce the different possible stem and progenitor niches, infer
the developmental “tree” structure, deduce the main regulation mechanisms, and estimate time scales within
hematpoiesis. In order to achieve these goals and link observations and data to mechanistic insight, we must
first achieve the specific aims of (I) developing both stochastic and deterministic cell count and clone count
models for hematopoiesis of barcoded HSCs, (ii) incorporate mechanisms of temporal variability into the
models, (iii) develop a probabilistic framework for clonal distributions in small blood samples, and (iv)
implement statistical tests of our models against data. Our hypothesis is that barcoding/tagging experiments
can be treated at the lowest order of approximation using a “neutral'' base model, upon which refinements can
be made to incorporate additional complexities such as cellular heterogeneity. The strategy is significant
because it allows us to formulate a high-dimensional mathematical framework that will be a general starting
point for analyzing long term clonal tracking experiments in which up to thousands of clone lineages are
tracked. The research is innovative for addressing high-dimensional clonal tracking data and advancing
parsimonious, yet informed multiscale models that allow inference of hematopoietic mechanisms.

## Key facts

- **NIH application ID:** 10122987
- **Project number:** 5R01HL146552-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** TOM CHOU
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $185,418
- **Award type:** 5
- **Project period:** 2019-04-15 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10122987

## Citation

> US National Institutes of Health, RePORTER application 10122987, Tracking clonal dynamics during hematopoiesis: mechanistic insight via modeling and data analysis (5R01HL146552-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10122987. Licensed CC0.

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