# Towards Understanding Molecular Mechanisms of Human Hematopoietic Stem Cells' Quiescence

> **NIH NIH R01** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2022 · $338,000

## Abstract

SUMMARY/ABSTRACT
Hematopoietic stem cells (HSCs) produce all blood lineages and replenish blood in response to loss or injury
throughout life. HSCs like most adult stem cells, are mainly quiescent. Quiescence is proposed to protect
HSCs from replicative and metabolic stress that would otherwise impact health and longevity, thereby
enabling them to maintain tissue homeostasis and allowing for the repair of defective/damaged tissue during
their lifetime. Progress in HSC-based therapies is partly hindered by lack of reliable approaches to modulate
HSC quiescence and activity. Thus, understanding the core molecular mechanisms of HSC quiescence is
fundamental for improving HSC health and longevity and has major translational implications for the clinic.
By applying a new approach based on mitochondrial membrane potential (MMP), we identified the most
dormant subsets of both human and mouse HSCs. Using this approach, we recently discovered that
lysosomal activity is pivotal for the maintenance of mouse HSC quiescence. Our findings suggest that
lysosomes dynamically regulate the hematopoietic stem cell switch between quiescent and active states.
Here, we propose to investigate lysosomal function and the effects of modulation of lysosomal activity on the
potency of human HSCs. These studies are likely to provide means towards extending the availability of
human HSCs. Overall, translation of our findings to human HSCs will build the foundation towards advancing
cell therapy.

## Key facts

- **NIH application ID:** 10346063
- **Project number:** 1R01HL161567-01
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** SAGHI GHAFFARI
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $338,000
- **Award type:** 1
- **Project period:** 2022-02-15 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10346063

## Citation

> US National Institutes of Health, RePORTER application 10346063, Towards Understanding Molecular Mechanisms of Human Hematopoietic Stem Cells' Quiescence (1R01HL161567-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10346063. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*