# Molecular regulation of native hematopoiesis

> **NIH NIH R01** · BOSTON CHILDREN'S HOSPITAL · 2022 · $722,872

## Abstract

SUMMARY
Decades of work have established a paradigm for hematopoietic regeneration and maintenance based on the
activity of multipotent hematopoietic stem cells (HSCs) at its apex. Our understanding of the fundamental
properties of HSCs and progenitor populations has been historically based on notions derived from
transplantation assays. Data over the last few years, however, have challenged the most fundamental aspects
of models based on these studies, and have raised biological questions that are of direct clinical relevance in
the hematology field. Additionally, it is now clear that intrinsic heterogeneity exists among seemingly pure
populations of HSCs and downstream progenitors. How the functionally distinct behavior of these
stem/progenitor cells is molecularly regulated and how individual clone size is controlled over time represent
important biological questions relevant to our understanding of normal and diseased hematopoiesis. Over the
past five years, my lab has developed novel single cell-based lineage tracing systems to study hematopoietic
biology in the non-transplanted individual, which we refer to as native hematopoiesis. With these tools, we
have shown that important biological differences exist between the source of hematopoietic cells and their
outcomes when comparing transplantation versus native blood physiology. More recently, we have coupled
lineage output readouts with molecular measurements at the single cell level, allowing us to identify
transcriptional features of stem/progenitor cells that carry distinct functional outcomes. In this renewal
application, we aim to utilize these high-resolution lineage-tracing tools to further characterize drivers of
functional HSC heterogeneity and aging in native hematopoiesis. First, we will functionally and
molecularly characterize a novel transcriptional regulator of the native HSC state, which we have identified
using our singe cell screens. Second, we will utilize a combination of single cell lineage tracing,
transcriptomics, and epigenomics to understand the molecular changes and clonal fluctuations that occur
during the aging process in the mouse. Third, we will adapt our single cell molecular tracing strategies to
characterize human hematopoiesis in a surrogate native state, and to identify potential novel regulators of
human HSC behavior. Our comprehensive and interdisciplinary studies will shed led on the cellular and
molecular mechanisms driving hematopoiesis in situ. Moreover, these studies will inform efforts to enhance
hematopoietic regeneration and prevent pre-malignant clonal hematopoiesis.

## Key facts

- **NIH application ID:** 10321680
- **Project number:** 5R01HL128850-06
- **Recipient organization:** BOSTON CHILDREN'S HOSPITAL
- **Principal Investigator:** Fernando Camargo
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $722,872
- **Award type:** 5
- **Project period:** 2016-02-15 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10321680

## Citation

> US National Institutes of Health, RePORTER application 10321680, Molecular regulation of native hematopoiesis (5R01HL128850-06). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10321680. Licensed CC0.

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