image: Rong Lu (left) and Michael Elowitz
Credit: Cristy Lytal/USC Stem Cell and Caltech
Is it possible to study the production of blood and immune cells inside the bone marrow? For the first time ever, the answer is yes, thanks to a new approach pioneered by USC Stem Cell scientist Rong Lu and Caltech synthetic biologist Michael B. Elowitz, together with co-investigators Carlos Lois and Lior Pachter at Caltech.
The new approach will enable the scientists to study the blood-producing stem and progenitor cells, also called hematopoietic stem and progenitor cells (HSPCs), within the difficult-to-access bone marrow—without needing to extract the cells. The goal is to glean insight into how the spatial arrangements of HSPCs influences their activity, interactions, and production of blood and immune cells.
Supported by a prestigious NIH Director’s Transformative Research Award for $8.1 million, their research project will enhance our understanding of blood cell regeneration within the native environment in the body. Their findings could inform efforts to optimize bone marrow transplantation and provide insights into a diverse array of health conditions, ranging from cancer to heart disease to chronic liver disease.
Lu and Elowitz began their collaboration in 2020, when USC Stem Cell awarded them a $200,000 Broad Innovation Award, designed to bring together teams of engineers and scientists from USC and Caltech.
With support from the NIH’s Director’s Transformative Research Award, the team will continue their investigation on the spatial organization of HSPCs, which generate millions of blood and immune cells every second. In healthy individuals, HSPCs produce an ideal balance of various blood and immune cell types, allowing the body to perform many functions, including transporting oxygen and nutrients and fending off germs and cancers.
HSPCs reside in the bone marrow, which is a tightly packed, semi-fluid collection of dozens of cell types. Because bone marrow lacks a rigid structure and resides inside bone cavities, it’s difficult to observe and study the complex and ever shifting spatial relationships and interactions between its resident HSPCs.
By leveraging a new technology called MEMOIR that tracks the relationships of cells, new transgenic mice, and computational approaches, the scientists will pinpoint the locations of specific HSPCs and other bone marrow cell types, while simultaneously gathering information about their interactions and lineage relationships. This could link cell-cell interactions of HSPCs with their proliferation and differentiation, providing important insights into why certain HSPCs are dominant in replenishing the majority of blood and immune cells after bone marrow transplantation.
“We’re excited to apply these new technologies to study the complex interactions of HSPCs within the context of their native environment in the bone marrow,” said Elowitz, who is the Roscoe Gilkey Dickinson Professor of Biology and Bioengineering at Caltech, and a Howard Hughes Medical Institute Investigator.
Lu, an associate professor of stem cell biology and regenerative medicine, biomedical engineering, medicine, and gerontology at the Keck School of Medicine of USC added: “This research will provide unprecedented insights into how spatial context might determine which HSPCs are dominant in producing blood and immune cells. These insights have the potential to advance our understanding of the diseases that can develop when some HSPCs become too dominant, such as leukemia, as well as to guide efforts to improve bone marrow transplantation.”
The Transformative Research Award promotes cross-cutting, interdisciplinary approaches and is open to individuals or teams who propose research that could potentially create or challenge existing paradigms. The award is managed by the High-Risk, High-Reward Research program, which recognizes exceptionally creative scientists pursuing highly innovative research with the potential for broad impact in biomedical, behavioral, or social sciences. The program is supported by the NIH Common Fund, which pursues major opportunities and gaps in biomedical research that require NIH-wide collaboration to succeed.
Through the Transformative Research Award, Lu and Elowitz’s project will be supported by NIH grant R01 DK143671-01.
“We’re so proud that these shining stars, Drs. Lu and Elowitz, have received the prestigious NIH Director’s Transformative Research Award,” said Charles (Chuck) Murry, Chair of the Department of Stem Cell Biology and Regenerative Medicine, and Director of the Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at USC. “Theirs is one of several innovative collaborations that USC Stem Cell enjoys with our neighbors at Caltech. It’s emblematic of our commitment to working across disciplines and across institutions to accelerate scientific discovery, and it’s exactly what we need to be doing more of.”