Environmental factors instruct lineage choice of blood progenitor cells

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 environmental factors influence human development. Likewise, the same 'nature vs. nurture' issue is debated by hematologists and stem cell researchers: Is multipotent progenitor cell differentiation 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, progenitor cells 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 stem cells."

Original publication: Rieger MA, Hoppe PS, Smejkal BM, Eitelhuber AC & Schroeder T (2009): Hematopoietic cytokines can instruct lineage choice. Science 325:217-218

Directed by Professor Magdalena Götz, the Institute of Stem Cell Research at Helmholtz Zentrum München combines research on stem cells of the nervous system, the hematopoietic system and of the endoderm. Especially in view of clinical applications, the objective of the Institute is to elucidate the underlying mechanisms for the specification of stem cells in order to utilize these in a targeted manner to repair damaged cells.

Helmholtz Zentrum München is the German Research Center for Environmental Health. As leading center oriented toward Environmental Health, it focuses on chronic and complex diseases which develop from the interaction of environmental factors and individual genetic disposition. Helmholtz Zentrum München has around 1680 staff members. The head office of the center is located in Neuherberg to the north of Munich on a 50-hectare research campus. Helmholtz Zentrum München belongs to the Helmholtz Association, Germany's largest research organization, a community of 16 scientific-technical and medical-biological research centers with a total of 26,500 staff members.

Sven Winkler, Helmholtz Zentrum München – German Research Center for Environmental Health, Ingolstädter Landstr. 1, 85764 Neuherberg, Germany. Phone: +49(0)89-3187-3946. Fax +49(0)89-3187-3324, email: presse@helmholtz-muenchen.de