Environmental factors instruct lineage choice of blood progenitor cells

Jul 15, 2009

The research team led by Dr. Timm Schroeder, stem cell researcher at Helmholtz Zentrum Muenchen, Germany, has developed a new bioimaging method for observing the differentiation of hematopoietic progenitor cells (HPC) at the single-cell level. With this method the researchers were able to prove for the first time that not only cell-intrinsic mechanisms, but also external environmental factors such as growth factors can control HPC lineage choice directly.

The findings, published in the current issue of the prestigious journal Science, provide an essential building block for understanding the molecular mechanisms of hematopoiesis and are an important prerequisite for optimizing therapeutic stem cell applications.

For decades scientists from various disciplines have discussed to what respective extent genetic predisposition and influence human development. Likewise, the same 'nature vs. nurture' issue is debated by hematologists and stem cell researchers: Is multipotent progenitor influenced solely by cell-intrinsic mechanisms or is it also influenced by the environment of the cell? What role do growth factors such as cytokines play? Do they influence HPC lineage choice directly or do they merely regulate the survival of the cell after the lineage choice has been made? Despite the immense importance of cytokines for day-to-day clinical research - and not least their far-reaching significance commercially - this issue has been one of the key unknown factors in the stem cell biology of blood.

"This is simply because until now we did not have the suitable technology to observe the processes of cell differentiation and to measure them quantitatively," explained Dr. Timm Schroeder, research group leader at the Institute of Stem Cell Research of Helmholtz Zentrum München. "We didn't know exactly what happens during this time span," Dr. Schroeder said. "That is why until now we could not prove what role cytokines play."

With the new bioimaging techniques developed by Dr. Schroeder's team, could be observed for a longer period and on the single-cell level. Depending on the kind of cytokines present, after a few days the HPC cultures contained only one cell type. The question remained unanswered whether this was a consequence of direct cytokine regulation or merely the result of sorting out "erroneously differentiated" cells by cell death. Using the new bioimaging techniques for continuous single-cell observation, Dr. Michael Rieger and students in Dr. Schroeder's research group showed for the first time that no cell death could be detected during the entire cell differentiation process. This proves unambiguously that HPC lineage choices can be steered by external environmental factors such as in this case by cytokines. The hematopoietic progenitor cells are "instructed" by cytokines.

"These findings confirm that signaling pathways that are activated by cytokine receptors influence the lineage choices of the cells," Dr. Schroeder said. "The new method offers us the unique chance to observe the effect of all the molecules involved in the differentiation process separately and to better understand their role. This is an important requirement for optimizing the therapeutic use of ."

Source: Helmholtz Zentrum München

Explore further: A novel therapy for sepsis?

add to favorites email to friend print save as pdf

Related Stories

Last step leading to blood cell formation elucidated

Apr 01, 2009

A team of scientists led by Dr. Timm Schroeder of Helmholtz Zentrum Muenchen, Germany, has proved the existence of hemogenic endothelial cells. The findings answer the question -- unsolved until now -- of how blood cells ...

'Fingerprints' help find genes involved in differentiation

Nov 14, 2007

A database that includes the molecular profiles of the major components of the blood system – including the stem cells and the cells differentiated from them – enabled researchers at Baylor College of Medicine (BCM) in ...

Enzyme plays key role in cell fate

Jun 04, 2008

The road to death or differentiation follows a similar course in embryonic stem cells, said researchers at Baylor College of Medicine in Houston in a report that appears online today in the journal Cell Stem Cell.

Forever young: Differentiation blocked in tumor stem cells

Jan 07, 2008

A new comparison of normal stem cells and cancer stem cells reveals that the cancer stem cells are abnormally trapped at an early stage of development. The research, published by Cell Press in the January issue of Cancer Ce ...

Recommended for you

A novel therapy for sepsis?

4 hours ago

A University of Tokyo research group has discovered that pentatraxin 3 (PTX3), a protein that helps the innate immune system target invaders such as bacteria and viruses, can reduce mortality of mice suffering ...

Cellular protein may be key to longevity

Sep 15, 2014

Researchers have found that levels of a regulatory protein called ATF4, and the corresponding levels of the molecules whose expression it controls, are elevated in the livers of mice exposed to multiple interventions ...

Gut bacteria tire out T cells

Sep 15, 2014

Leaky intestines may cripple bacteria-fighting immune cells in patients with a rare hereditary disease, according to a study by researchers in Lausanne, Switzerland. The study, published in The Journal of Experimental Me ...

User comments : 0