# Deletion of von-Hippel Lindau gene in Dmp1 expressing cells impairs hematopoiesis

> **NIH NIH F31** · UNIVERSITY OF CALIFORNIA, MERCED · 2021 · $36,901

## Abstract

PROJECT SUMMARY
My long-term objective is to characterize the microenvironment that influences hematopoiesis in the context of
altered bone homeostasis. Hematopoietic stem cells (HSCs) continuously replenish blood cells by differentiation
and maturation into either the lymphoid or myeloid lineage. Lymphoid lineage cells include B lymphocytes
are required for the production of antibodies that are crucial for a robust adaptive immune response, while
myeloid lineage cells include erythrocytes (red blood cells), platelets essential to stop bleeding,
granulocytes and macrophages which are crucial components of innate immunity. The microenvironment in the
bone marrow (BM) that supports conventional B cell (also called “B2” cells) development and myeloid
development has been described (3-9), but the detailed contributions of the microenvironment that maintain
and that regulate B cell development and myeloid-erythroid development in the bone marrow remain
unknown. My aim is to fill the scientific knowledge gap on the microenvironmental niches that influence the
maintenance and function of B cells, myeloid cells and erythrocytes. In the course of this study to examine
the effects of altered bone homeostasis on immune cell development, my laboratory discovered that B cell
development was severely impaired in mice in which a hypoxia response pathway gene, von-Hippel Lindau
(Vhl), is conditionally deleted in osteocytes (10). I hypothesize that Vhl-deficiency in osteocytes results in
structural and molecular changes in the BM microenvironments that insufficiently produces niche cells
and cytokines required to appropriately support hematopoiesis in the BM. In support of this hypotheses, my
preliminary analyses suggest that deletion of Vhl in osteocytes results in a decrease of endothelial cells,
mesenchymal stem cells and osteoblasts. My project objective is to further characterize the osteocyte-
regulated microenvironmental influences on the development and maintenance of 1) B lymphocytes and 2)
myeloid-erythroid development due to Vhl deficiency. I plan to utilize immunoassays, co-culture methods,
and transplantation strategies to characterize the Vhl deficient bone marrow microenvironment. This
information could be applied to future studies of the effects of irradiation, myeloablative conditioning, or
bone-building drugs on bone marrow niches and immune cell development.

## Key facts

- **NIH application ID:** 10234889
- **Project number:** 1F31AI154815-01A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, MERCED
- **Principal Investigator:** Betsabel Chicana
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $36,901
- **Award type:** 1
- **Project period:** 2021-08-17 → 2022-08-16

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10234889

## Citation

> US National Institutes of Health, RePORTER application 10234889, Deletion of von-Hippel Lindau gene in Dmp1 expressing cells impairs hematopoiesis (1F31AI154815-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10234889. Licensed CC0.

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