# Mapping the unique features of fetal and neonatal hematopoietic stem and progenitor cells conferring susceptibility to inflammation and infection

> **NIH NIH K08** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2020 · $166,956

## Abstract

PROJECT SUMMARY
 Neonatal sepsis is a significant global health burden, with 1.4 million newborns dying annually and many
more with substantial lifelong health problems as a consequence of inflammation and infection. Neonates are
uniquely susceptible to sepsis in part due to an immune response that fails to adequately control invading
pathogens. In particular, the marked neutropenia characteristic of the neonatal response to infection is a primary
contributor to mortality in newborns that rarely occurs in adults. Adult hematopoietic stem cells (HSCs) sit at the
top of the hematopoietic hierarchy, giving rise to all lineages of the blood system including neutrophils, and
responding to inflammatory signals to regenerate the blood system according to demand. This is achieved
through the dynamic production of different multipotent progenitor (MPP) subsets with distinct baseline
predispositions toward certain lineages of blood cells but substantial plasticity such that their relative frequency
and lineage potentiality is modified by inflammatory signals. Whether fetal and neonatal HSCs give rise to similar
MPP subsets, and whether these perinatal MPP subsets respond to inflammation to rebuild the blood system in
the same way as adult populations is not known. This is a fundamental gap in our understanding of perinatal
hematopoiesis that significantly impairs our ability to diagnose and treat neonatal sepsis. This proposal
represents a four year career development plan aimed at filling that gap in two important ways. First, the research
strategy proposed in this application will establish a comprehensive roadmap of perinatal HSC/MPP biology
using mouse models as a template for future analyses of human HSC/MPP populations for translational studies.
In Specific Aim 1, we will evaluate HSC/MPP function in the fetus and neonate through in vitro assays and in
vivo transplantation approaches to assess their lineage contributions and regenerative potential, and use
unbiased RNA-seq transcriptomic profiling to investigate the molecular mechanisms regulating their function
during unperturbed development. In Specific Aim 2, we will determine the ability of perinatal HSC/MPPs to
mount an emergency myelopoietic response to inflammation and infection by dissecting individual responses to
key inflammatory cytokines such as IL-1, IL-6, IFNa, and TNFa and employing in vivo models of LPS and Group
B Streptococcus (GBS) chorioamnionitis and early onset sepsis. Second, the career development and training
activities outlined in this proposal will position the PI, Dr. Amélie Collins, for a life-long independent research
career investigating how the unique properties of perinatal hematopoiesis contribute to neonatal morbidities and
mortality. Dr. Collins is a neonatologist and Assistant Professor of Pediatrics at Columbia University Irving
Medical Center with significant background in immunology and human neonatal conditions. She will complement
that expertise with training...

## Key facts

- **NIH application ID:** 10127172
- **Project number:** 1K08DK124657-01A1
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Amelie Collins
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $166,956
- **Award type:** 1
- **Project period:** 2020-09-15 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10127172

## Citation

> US National Institutes of Health, RePORTER application 10127172, Mapping the unique features of fetal and neonatal hematopoietic stem and progenitor cells conferring susceptibility to inflammation and infection (1K08DK124657-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10127172. Licensed CC0.

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