The objective of this project is to utilize high dimensional single cell approaches to delineate the spatial architecture of human bone marrow. Functions of hematopoietic stems cells are known to be modulated by signals generated by stromal cells in the bone marrow. Geographic relationships between hematopoietic cells and specific stromal cell populations are thought to be a critical component of this interaction. While studies in animal models have elucidated many of these key relationships, similar studies in human bone marrow have been limited. We therefore propose to utilize imaging mass cytometry (IMC) to directly interrogate the cellular architecture of the human bone marrow microenvironment. We will couple this approach with single cell RNA sequencing to enable the identification of novel markers of specific stromal cell populations. These findings will be leveraged to further inform the IMC approach. Within this context, we will develop a road map of normal human bone marrow, which can serve as the framework for subsequent studies of both normal and diseased hematopoietic states.

Public Health Relevance

This study will delineate the spatial hierarchy of human bone marrow, thereby providing critical information to better understand mechanisms of hematopoiesis in a variety of settings, including aging, impact of gender, and in the context of hematopoietic disorders including hematopoietic malignancies.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21HL150636-02
Application #
10115110
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Bai, C Brian
Project Start
2020-03-01
Project End
2022-02-28
Budget Start
2021-03-01
Budget End
2022-02-28
Support Year
2
Fiscal Year
2021
Total Cost
Indirect Cost
Name
Washington University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130