New And Complex Circuitry Revealed By Global View Of Blood Cell Development

January 28, 2011

BlankNew And Complex Circuitry Revealed By Global View Of Blood Cell Development

22 Jan 2011

A small pool of stem cells replenishes the human body with about 200 billion new

blood cells daily. But the elaborate circuitry that determines if a cell will

develop into a T cell, red blood cell, or one of the nine or more other blood

cell types remains largely unknown. A research team led by scientists from the

Broad Institute and Brigham and Women's Hospital has taken a systematic approach

to help decipher this circuitry, compiling a comprehensive catalog of the

factors that determine a blood cell's fate. Their work appears in the January 21

issue of Cell.

The researchers found that blood cells are directed by a multitude of

transcription factors, proteins that turn on and off genes. While many previous

studies have focused on individual transcription factors or types of blood

cells, this study examined the expression and regulation of all transcription

factors throughout blood development. The findings point to densely,

interconnected circuits that control this process, suggesting that the wiring

for blood cell fate is far more complex than previously thought.

" One assumption in the field had been that there are a small number of

transcription factors that orchestrate this process, " said Aviv Regev, a Broad

Institute core member and co-senior corresponding author of the study. " Some

people have always thought there would be a lot of factors and that it would

just take time to find them. It turns out there are more masters than we would

have thought. "

The researchers looked globally at how the expression of all 20,000 or so genes

in the genome change as blood stem cells become specialized cell types (a

process known as differentiation). They discovered that while a small fraction

of genes are uniquely expressed in a single type of cell, other genes are more

broadly expressed - present in a variety of cell types but at varying levels.

Some of these genes are turned on in the blood stem cells and switched off at

certain points in development while others are reused in several parallel

developmental branches. The researchers found about 80 of these patterns of

variable genes, called modules. Each kind of specialized cell has a unique

profile, or combination, of these modules.

Looking at the genes modulated in the course of healthy cell development could

give researchers clues about what events lead to blood cancers, such as

leukemia, a disease where differentiation has gone wrong.

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