Found Protein That Creates Fundamental Stem Cells in Blood

Revealing the Generation Principle of Stem Cells Producing Blood Cells like White Blood Cells
New Path for Stem Cell Treatment of Blood Diseases such as Leukemia and Hematologic Cancers

A comparison image showing normal zebrafish and Supt16h-deficient mutant zebrafish (top left) on the left, and the development of hematopoietic stem cells on the right.

[Asia Economy Reporter Junho Hwang] It has been revealed how hematopoietic stem cells, which produce blood cells such as white blood cells, red blood cells, and platelets, are generated. This research is expected to provide a new direction for regenerative therapies using hematopoietic stem cells as well as treatments for blood diseases such as leukemia and hematologic cancers.

The Molecular Genetics Team led by Research Fellow Yoonseong Lee of the Genome Homeostasis Research Group at the Institute for Basic Science, in collaboration with the University of California San Diego, announced that a type of histone chaperone protein called 'Supt16h' governs the development of hematopoietic stem cells. The research findings were published on the 24th in the international journal Nature Cell Biology.

Unveiling the Mechanism of Stem Cell Generation That Produces Blood Cells

Comparison of hematopoietic stem cell development between normal zebrafish and Supt16h-deficient mutant zebrafish.

The research team first identified genes that influence the generation of hematopoietic stem cells. They confirmed that Supt16h, one of the histone chaperone proteins that regulate histone proteins to prevent clumping or DNA strand entanglement, plays a key role in the development of hematopoietic stem cells.

This conclusion was drawn from next-generation sequencing analysis conducted on a zebrafish model, which shares genetic similarity with humans, where random mutations were induced to create defects in hematopoietic stem cells. The team explained, "We confirmed that mutations in the Supt16h gene cause loss of protein function," adding, "This means Supt16h plays a crucial role in hematopoietic stem cell development."

A New Chapter in Treating Blood Diseases Such as Leukemia and Hematologic Cancers

Schematic diagram of hematopoietic stem cell development mechanisms in normal zebrafish (left) and Supt16h mutant zebrafish

The researchers further investigated the effects of Supt16h deficiency on cell development. As a result, they found that when Supt16h levels decrease, the tumor suppressor gene p53 is excessively expressed, which in turn activates the gene phc1 that suppresses the Notch signaling pathway regulating cell development. This led to reduced expression of Notch genes and ultimately blocked the generation of hematopoietic stem cells. In other words, it was confirmed that Supt16h regulates hematopoietic stem cell generation by modulating Notch signaling through p53 mediation.

Research Fellow Yoonseong Lee stated, "This study revealed that the histone chaperone protein Supt16h controls gene expression essential for the development of specific organs and cells," adding, "We clarified that the p53-mediated Notch signaling system is important for hematopoietic stem cell development." He continued, "We expect this to be an important indicator not only for therapies using hematopoietic stem cells in regenerative medicine but also for improving treatments for blood diseases such as leukemia."

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