Scientists reprogram blood cells into blood stem cells in mice

PUBLIC RELEASE DATE:

24-Apr-2014

Contact: Irene Sege irene.sege@childrens.harvard.edu 617-919-3110 Boston Children's Hospital

BOSTON (April 24, 2014)Researchers at Boston Children's Hospital have reprogrammed mature blood cells from mice into blood-forming hematopoietic stem cells (HSCs), using a cocktail of eight genetic switches called transcription factors. The reprogrammed cells, which the researchers have dubbed induced HSCs (iHSCs), have the functional hallmarks of HSCs, are able to self-renew like HSCs, and can give rise to all of the cellular components of the blood like HSCs.

The findings mark a significant step toward one of the most sought-after goals of regenerative medicine: the ability to produce HSCs suitable for hematopoietic stem cell transplantation (HSCT) from other cell types, in particular more mature or differentiated cells.

The research team, led by Derrick J. Rossi, PhD, of Boston Children's Program in Cellular and Molecular Medicine, reported their work today online in the journal Cell.

HSCs are the basic starting material for HSCTs, regardless of their source (bone marrow, umbilical cord blood, peripheral blood). The success of any individual patient's HSCT is tied to the number of HSCs available for transplant: the more cells, the more likely the transplant will take hold. However, HSCs are quite rare.

"HSCs only comprise about one in every 20,000 cells in the bone marrow," says Rossi. "If we could generate autologous HSCs from a patient's other cells, it could be transformative for transplant medicine and for our ability to model diseases of blood development."

In their study, Rossi and his collaborators, including lead author Jonah Riddell, PhD, screened gene expression in 40 different types of blood and blood progenitor cells from mice. From this screen they identified 36 transcription factorsgenes that control when other genes are turned on and offthat are expressed exclusively in HSCs, not in cells that arise from them.

"Blood cell production invariably goes in one direction: from stem cells, to progenitors, to mature effector cells," Rossi explains. "We wanted to reverse the process and derive HSCs from differentiated blood cells using transcription factors that we found were specific to HSCs."

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Scientists reprogram blood cells into blood stem cells in mice