# Mechanical regulation of hematopoiesis

> **NIH NIH F32** · UT SOUTHWESTERN MEDICAL CENTER · 2024 · $74,284

## Abstract

PROJECT SUMMARY
 Mechanical loading of bones is important for healthy hematopoiesis and immune function. The bone
marrow is sensitive to loading-induced changes in interstitial flow and shear stress. The Leptin receptor-
expressing (LepR+) stromal cells in the bone marrow support both hematopoiesis and osteogenesis. Load-
bearing exercise promotes the maintenance of lymphoid progenitors in the bone marrow by promoting
signaling of the mechanosensitive ion channel Piezo1 in a subset of these cells: peri-arteriolar Osteolectin
expressing (Oln+) cells. The hypothesis of this proposal is that another mechanically regulated ion channel,
TREK1, contributes to the regulation of hematopoiesis and osteogenesis in the bone marrow. Trek1, an
outwardly rectifying potassium channel that is activated by mechanical stretch and pressure, is expressed by
most peri-arteriolar Oln+LepR+ cells and by a subset of other LepR+ cells. No one has investigated whether
TREK1 regulates hematopoiesis or osteogenesis under physiological conditions. In Aim 1, I propose to test
whether Trek1 expression in peri-arteriolar Oln+LepR+ cells and peri-sinusoidal Oln-LepR+ cells regulates
hematopoiesis in the bone marrow. In Aim 2, I propose to test whether Trek1 expression in peri-arteriolar
Oln+LepR+ cells and peri-sinusoidal Oln-LepR+ cells regulates osteogenesis in the bone marrow and whether
this is modulated by mechanical loading. In Aim 3, I will test whether Trek1 expression defines a biologically or
spatially distinct subset of LepR+ stromal cells in the bone marrow. I will test how the deficiency of Trek1
affects hematopoietic stem/progenitor cell frequency, osteogenesis, and bone marrow reconstitution capacity.
Outcomes of the proposed studies will indicate whether Trek1 modulates hematopoiesis or osteogenesis in
response to mechanical loading and whether Trek1-expressing cells perform distinct functions in the bone
marrow niche.

## Key facts

- **NIH application ID:** 10997137
- **Project number:** 1F32HL168918-01A1
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** Jasmine Shirazi
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $74,284
- **Award type:** 1
- **Project period:** 2024-09-01 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10997137

## Citation

> US National Institutes of Health, RePORTER application 10997137, Mechanical regulation of hematopoiesis (1F32HL168918-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10997137. Licensed CC0.

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