# Development of the resident macrophage lineage in mouse and human

> **NIH NIH R01** · SLOAN-KETTERING INST CAN RESEARCH · 2024 · $709,136

## Abstract

Title:
Development of the resident macrophage lineage in mouse and human
Summary/abstract
Our long-range goal in our previous funded RO1 application was to elucidate mechanisms that underlie the
development and specification of embryo-derived tissue-resident macrophages in mice. Our program of work
aimed to understand how the identities and functions of resident macrophages are specified and to provide tools
and concepts to identify pathophysiological mechanisms underlying their roles in developmental, inflammatory,
degenerative and tumoral diseases. This work allowed us to identify key novel functions of resident macrophages
and mechanisms that underly these functions and to develop new genetically tractable models which pave the
way for our current project. Yet, a comprehensive understanding of the developmental origin and functions
of mammalian resident macrophages, which has essential implications for genetic and pharmacological
investigations of their specialized functions, still faces several important challenges, which are identified
and addressed in this renewal proposal. 1) The development of resident macrophage in mice cannot be
directly extrapolated to humans because the earlier steps of extraembryonic hematopoiesis and macrophage
development present with differences among vertebrates, for example between Zebrafish and mice, and are
overall poorly understood. Notably, 2) the early hemato-endothelial progenitor(s) that give rise to EMPs and
HSCs are still elusive, which impairs our ability to fully characterize resident macrophages. In addition, 3) it is
important to elucidate the roles of individual LDTFs and their subset-specific combinations for the control of
tissue-specific functions of macrophages, because, in addition to identify molecular mechanisms that underly
macrophage functions, these studies have the potential to unveil therapeutic strategies for leveraging
macrophage functions in human. We propose to take advantage of novel genetic tools to identify the hemato-
endothelial progenitors that generate the macrophage lineage in mice (AIM1), to identify conserved
macrophages progenitors in human using a genetically tractable model for hematopoietic differentiation in human
induced pluripotent stem cell (hiPSC)-derived embryoid bodies, and to take advantage of this versatile in vitro
model to characterize the role of macrophage LDTFs in the control of macrophage tissue-specific functions
(AIM2). We expect that our results will provide a robust experimental basis to transform and improve our
understanding of the cellular, genetic, and molecular determinants of resident-macrophage development in mice
and, importantly, in human, and provide important genetic tools for the molecular understanding and
manipulation of their functions in physiology and diseases.

## Key facts

- **NIH application ID:** 10767992
- **Project number:** 5R01AI130345-07
- **Recipient organization:** SLOAN-KETTERING INST CAN RESEARCH
- **Principal Investigator:** Frederic Geissmann
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $709,136
- **Award type:** 5
- **Project period:** 2017-02-08 → 2027-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10767992

## Citation

> US National Institutes of Health, RePORTER application 10767992, Development of the resident macrophage lineage in mouse and human (5R01AI130345-07). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10767992. Licensed CC0.

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