# Mitochondrial Regulation of Hematopoietic Stem Cells

> **NIH NIH R01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2022 · $689,625

## Abstract

Hematopoietic stem cells (HSCs) reside in the bone marrow (BM), are quiescent, can self-renew, and generate
all lineages of the hematopoietic system. A coherent picture of how steady-state function and homeostatic
responses of HSCs are regulated has not emerged yet, however. Furthermore, although progress has been
made in this area, reliable renewal or even maintenance of HSCs in vitro remains challenging, but would have
major translational implications. A particular gap is our understanding of the organellar cell biology of HSCs. One
organelle of which role in HSCs is unclear is the mitochondrion. Preferential use of glycolysis in stem cells
suggests that mitochondrial respiration is more dispensable for HSCs than for progenitors. These findings raise
the question whether mitochondria play roles in HSCs that are not directly related to ATP production, such as
intermediary metabolism, epigenetics, apoptosis and intracellular calcium handling. Mitochondria dynamics, the
fusion and fission of mitochondria, play a central role in the coordination of mitochondrial function. The fusion
machinery consists of two partially redundant and interacting outer membrane GTPases, mitofusins (MFN) 1
and 2, and the inner membrane GTPase, OPA1. We observed that mitofusins show redundant and non-
redundant as well as cell-intrinsic and cell-extrinsic roles that profoundly and specifically impact HSCs. We also
found that HSCs are endowed with elevated mitochondrial mass and attenuated mitophagy, and that all mitofusin
mutants with severe phenotypes also had reduced mitochondrial mass in HSCs, but not in mature hematopoietic
cells. The goal of this proposal is to elucidate the underlying mechanisms and harness mitochondrial dynamics
to achieve more efficient maintenance of HSC in vitro.

## Key facts

- **NIH application ID:** 10375950
- **Project number:** 2R01HL135039-05
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** HANS-WILLEM E SNOECK
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $689,625
- **Award type:** 2
- **Project period:** 2017-01-17 → 2025-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10375950

## Citation

> US National Institutes of Health, RePORTER application 10375950, Mitochondrial Regulation of Hematopoietic Stem Cells (2R01HL135039-05). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10375950. Licensed CC0.

---

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