# Mitochondrial regulation of hematopoietic stem cells

> **NIH NIH R01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2020 · $450,213

## Abstract

Hematopoietic stem cells (HSCs) reside in the bone marrow (BM), are quiescent, can self renew, and
generate all lineages of the hematopoietic system. Despite significant progress in our understanding of
mechanisms involved in self-renewal, differentiation and quiescence, a coherent picture of how these
mechanisms act in concert to regulate steady-state function and homeostatic responses of HSCs in vivo has
not emerged yet. Furthermore, reliable renewal of HSCs in vitro has not been achieved, while there is
overwhelming evidence that HSC self-renewal occurs in vivo. This implies that despite the identification of
dozens of cytokines and of more than 200 genes that affect HSC function in knockout studies, and despite the
publication of multiple studies on genome-wide expression and epigenetic signatures, significant gaps in our
understanding remain. A particular gap is our understanding of the organellar cell biology of HSCs. HSCs rely
predominantly on glycolytic ATP production, while many mature cells use mitochondrial oxidative
phosphorylation (OXPHOS). Preferential use of glycolysis in stem cells suggests that mitochondrial respiration
is more dispensable for HSCs than for progenitors, a notion supported by experimental data. These findings
raise the question whether mitochondria play a role in HSCs that is not directly related to ATP production. In
addition to ATP production, mitochondria are also required for several biosynthetic pathways and intermediary
metabolism, apoptosis and intracellular calcium homeostasis. We show in our preliminary data that
mitochondria are regulated in an exceptional fashion in HSCs, and that interfering with this regulation affects
HSC function, at least in part by buffering intracellular calcium (Cai2+), which we found to be strikingly low in
HSCs compared to progenitors and non-hematopoietic cells. The goal of is the proposal is to better define
regulation of mitochondria in HSC, its impact on Cai2+, and HSC on maintenance, identity and function.

## Key facts

- **NIH application ID:** 9844490
- **Project number:** 5R01HL135039-04
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** HANS-WILLEM E SNOECK
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $450,213
- **Award type:** 5
- **Project period:** 2017-01-17 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9844490

## Citation

> US National Institutes of Health, RePORTER application 9844490, Mitochondrial regulation of hematopoietic stem cells (5R01HL135039-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9844490. Licensed CC0.

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