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HemaCare Immune Cells Facilitate Study on Gene Activation During Stem Cell Development

Jan 15, 2019 10:04:00 AM / by Nancy Andon, MSc

Genes under magnifying glass-1A recent independent study cites using HemaCare-sourced immune cells to investigate a protein involved in gene activation during hematopoietic stem cell (HSC) development. [1]

The study, published by scientists at the Yokohama Institute in Japan, is focused on the function of a protein known as RUNX1. The reason RUNX1 is of particular interest is that it’s implicated in the development of a number of different types of cancer, including breast cancer, skin cancer, and acute myeloid leukemia. [2] In the latter case, defects in the gene that codes for the RUNX1 protein disrupt stem cell differentiation. This means that instead of normal development into mature cell types, there is a massive build-up of blast cells in the bone marrow, which is the hallmark of leukemia. Scientists have known since 2001 [3] that the RUNX1 protein is involved in the differentiation of hematopoietic stem cells into mature blood cells. But in order to target RUNX1’s role in cancer development, researchers need a much more in-depth knowledge of exactly how the protein is exerting its function.

The work at the Yokohama Institute is focused on investigating both how mistakes in a gene can cause defects that result in diseases like cancer, as well as how mistakes in the proteins that regulate a gene can cause disease. As a stem cell develops, it will need to turn different genes on and off to make sure it matures into the correct cell line; for example, an immune cell rather than a red blood cell. One of the key ways this is accomplished is called “methylation”.  Basically, small chemical tags called “methyl groups” are attached to individual genes. The presence of this tag keeps the gene turned off. Removing the tag through “demethylation” turns that gene on, so that it can play its role in the cell’s development.

The authors surmised that the RUNX1 protein was somehow using this mechanism to direct gene expression during stem cell development. To puzzle out exactly what was going on, the group obtained HSCs, as well as two well-characterized immune cells types, CD3+ T cells and CD19+ B cells, both sourced from HemaCare. HSCs can form T cells and B cells during normal development when specific genes are turned on. Careful experimentation showed that the RUNX1 protein was actually recruiting DNA-regulating proteins in the HSCs to specific methylation sites. This activity helped control development of the HSCs into different cell types. This is the first direct evidence of the involvement of RUNC1 in site-specific gene regulation.

Unearthing the details of stem cell development helps scientists pinpoint when and where something goes wrong. Understanding how cancer and other diseases develop at the cellular level will give us additional and potentially better ways of fighting these diseases.

Reference:

  1. Suzuki T, et al. RUNX1 regulates site specificity of DNA demethylation by recruitment of DNA demethylation machineries in hematopoietic cells. Blood Advances. 1:1699-1711. 2017.
  2. Koboldt DC. Comprehensive molecular portraits of human breast tumours. Nature. Nature Publishing Group. 490 (7418): 61–70. 2012.
  3. Okuda T, et al. RUNX1/AML1: a central player in hematopoiesis. International Journal of Hematology. 74 (3): 252–7. Oct. 2001.

Topics: genes, Stem Cells

Nancy Andon, MSc

Written by Nancy Andon, MSc

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