# The role of macrophages during hematopoietic stem cell emergence

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2020 · $190,487

## Abstract

Project Summary
In all vertebrate animals studied, the homeostasis of adult blood and immune cells is ultimately
maintained by rare subsets of hematopoietic stem cells (HSCs). During a brief window during
embryonic development, these HSCs arise de novo from hemogenic endothelium comprising the floor
of the dorsal aorta (DA) in a process that appears to be conserved amongst all vertebrates. A more
complete understanding of the signaling pathways that instruct HSC emergence could in principle
inform in vitro approaches utilizing pluripotent precursors to create patient-specific HSCs. This would
enable autologous transplantation strategies to combat a multitude of disorders including
hematopoietic neoplasms, solid cancers, immune deficiencies, and anemia without the currently
common complications of immune rejection or graft-versus-host disease. Despite decades of efforts,
this goal has not yet been achieved, in part due to an incomplete understanding of the native
molecular cues needed to establish HSC fate.
 The signaling events underlying the developmental specification of hemogenic endothelium
remain poorly understood. We recently made the surprising discovery that proinflammatory signaling,
in the absence of infection, is required for proper HSC emergence. These findings led us to study the
Progranulin factors, which serve to regulate the inflammatory response in other settings. Our
preliminary data indicate that the Progranulin-a protein is required for normal HSC development.
Interestingly, during this temporal window Pgrna is expressed only by macrophages. Our preliminary
data suggest that a specific macrophage subset derived from the erythromyeloid progenitor
expresses Pgrna. These findings suggest that a specific population of macrophages is required for
the normal development of HSCs through the function of Pgrna. These are novel findings indicating
that the lineal ontogeny of macrophages dictates specific functions, and will better inform us as to
how the embryo generates HSC fate.
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## Key facts

- **NIH application ID:** 9825509
- **Project number:** 5R21AI137575-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** David Traver
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $190,487
- **Award type:** 5
- **Project period:** 2018-11-19 → 2020-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9825509

## Citation

> US National Institutes of Health, RePORTER application 9825509, The role of macrophages during hematopoietic stem cell emergence (5R21AI137575-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9825509. Licensed CC0.

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