Using Genetic Cartography to Map Cell Lineage

Credits; TheScientist

Hematopoietic stem cells (HSC) are cellular factories that churn out blood and immune cells, but their production output varies significantly. This variation influences the success of bone marrow transplant therapies, which are heavily dependent on the quantity and type of blood cells in donor HSC transplantation. Although gene expression influences cell lineage, the regulatory mechanism remains unclear.

“This is an example where therapeutic usage precedes our understanding of the fundamental mechanism. [HSC] are clinically proved to be useful, so it really drives further research to better understand their regulation,” remarked Rong Lu, a stem cell biologist at the University of Southern California.

When investigating HSC regulation to improve immune regeneration, Lu and her team identified associations between gene activity that modulate the variety and amount of immune cell production.  Their findings, published in Science Advances, provide insights into how distinct genetic features can improve optimization of donor cell pools for therapies.

Lu wondered whether differences across individual HSC were intrinsic or influenced by their environment. To test this, the researchers infected HSC with lentivirus carrying unique genetic barcodes to track individual cells. This method enabled Lu to measure the quantity and type of cellular production.3 Lu focused on granulocytes and B cells, which are the most abundant myeloid and lymphoid immune cells, respectively.

In a one-to-multiple transplantation experiment, they injected barcoded HSC clones into a primary mouse recipient. After recovering the same stem cells, the researchers transplanted them into several other mice. Even with radiation or chemo treatment before transplantation, the blood production levels in the secondary mice remained consistent; these results implied that an inherent factor dictates blood producing capacity.

“The key technical challenge is being able to connect the cell and cell production tracking with the gene expression of the corresponding cells,” said Lu.

 

 

By Laura Tran, PhD

Article can be accessed on: The Scientist