# SHP2's Regulation of the Bone Marrow Stroma and Hematopoietic Crosstalk

> **NIH NIH R01** · RHODE ISLAND HOSPITAL · 2024 · $493,310

## Abstract

(PLEASE KEEP IN WORD, DO NOT PDF) (Enter the text here that is the new abstract information for your application. This section must be no longer than 30 lines of text.)
It has been reported that depletion of RUNX21 or LepR2 in mesenchymal stem/progenitor cells (MSPCs) reduces bone mass and increases bone marrow (BM) adipocytes (BMA), and that PDGFRβ activation drives MSPC expansion and BM vasculogenesis, finally influencing hematopoiesis3. Our preliminary data show that mice lacking SHP2 in the Osterix+ stromal progenitor cells (O+SPCs) have similarly increased BMA and BM vasculature and skewed lymphopoiesis. We have not yet determined the molecular mechanism(s) by which SHP2 exerts its influence on O+SPCs and hematopoietic cells. However, the phenotypic similarity of mice lacking SHP2, RUNX2, LepR, or PDGFR in O+SPCs leads us to hypothesize that SHP2 influences the osteogenic, adipogenic and/or stromogenic fate of O+SPCs by modifying the transcription activity of RUNX2 and the kinase activity of PDGFR, and that altered BM O+SPCs change the cellular and molecular constituents of the BM niche and subsequently hematopoiesis. To test this novel hypothesis, we will complete two specific aims. In Aim 1 we will interrogate the impact of SHP2 depletion on RUNX2 transcriptional activity in O+SPCs, while in Aim 2 we will determine the effect of SHP2 depletion on stromogenic differentiation of O+SPCs and hematopoisis in vitro and in vivo. O+SPCs participate in BM hematopoietic niche construction and maintenance, and both SHP2 and RUNX2 influence O+SPCs. This innovative study will yield foundational information regarding SHP2’s regulatory role in O+SPCs and its consequent role in hematopoiesis and BM vasculogenesis. This information will significantly advance our understanding of the effect and importance of crosstalk between BM stromal cells and hematopoietic cells, and hematopoietic malignancy.

## Key facts

- **NIH application ID:** 10826307
- **Project number:** 1R01DK138630-01
- **Recipient organization:** RHODE ISLAND HOSPITAL
- **Principal Investigator:** Wentian Yang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $493,310
- **Award type:** 1
- **Project period:** 2024-08-15 → 2027-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10826307

## Citation

> US National Institutes of Health, RePORTER application 10826307, SHP2's Regulation of the Bone Marrow Stroma and Hematopoietic Crosstalk (1R01DK138630-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10826307. Licensed CC0.

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