Study demonstrates cells can acquire new functions through transcriptional regulatory network
Researchers at the RIKEN Omics Science Center (OSC) have successfully developed and demonstrated a new experimental technique for producing cells with specific functions. As an alternative to induced pluripotent stem cells, the technique promises to enable faster production of functional cells for use in cancer therapy and other areas.
Starting with the first-ever production of induced pluripotent stem cells (iPS cells) in 2006, cell reprogramming - the genetic conversion of cells from one type to another - has revolutionized stem cell research and opened the door to countless new medical applications. Inducing such reprogramming, however, is difficult, inefficient and time-consuming, involving a largely hit-or-miss process of selecting candidate genes.
In the current study, the OSC research team explored an alternative to iPS cells based on the use of transcriptional regulatory networks (TRNs), networks of transcription factors and the genes they regulate. Previous research by the team characterized the dynamic regulatory activities of such transcription factors during cellular differentiation from immature cell (monoblast) to developed (monocyte-like) cell using human acute monocytic leukemia cell lines (THP-1). Their findings led them to hypothesize that functional characteristics of the cell-type are maintained by its specific TRN.
Their new paper builds on this hypothesis, establishing a series of new methods for identifying transcription factors (TFs) for the monocyte network, which play a key role in inducing cell-specific functions. Four core TF genes of the monocyte TRN, identified using this approach, were introduced into human fibroblast cells, expression of which activated monocytic functions including phagocytosis, inflammatory response and chemotaxis. Genome-wide gene expression analysis of this reprogrammed cell showed monocyte-like gene expression profile, demonstrating that reconstruction of a functional TRN can be achieved by introducing core TRN elements into unrelated cell types.
Published in the journal PLoS ONE, the newly-developed methods open the door to a new form of direct cell reprogramming for clinical use which avoids the pitfalls of embryonic stem (ES) and induced pluripotent stem (iPS) cells, charting a course toward novel applications in regenerative medicine and drug discovery.
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Takahiro Suzuki, Mika Nakano-Ikegaya, Haruka Yabukami-Okuda, Michiel de Hoon, Jessica Severin, Satomi Saga-Hatano, Jay W. Shin, Atsutaka Kubosaki, Christophe Simon, Yuki Hasegawa, Yoshihide Hayashizaki, Harukazu Suzuki "Reconstruction of Monocyte Transcriptional Regulatory Network Accompanies Monocytic Functions in Human Fibroblasts." PLoS ONE, 2012, DOI: 10.1371/journal.pone.0033474
RIKEN is Japan's flagship research institute devoted to basic and applied research. Over 2500 papers by RIKEN researchers are published every year in reputable scientific and technical journals, covering topics ranging across a broad spectrum of disciplines including physics, chemistry, biology, medical science and engineering. RIKEN's advanced research environment and strong emphasis on interdisciplinary collaboration has earned itself an unparalleled reputation for scientific excellence in Japan and around the world.
About the RIKEN Omics Science Center (OSC)
Omics is the comprehensive study of molecules in living organisms. The complete sequencing of genomes (the complete set of genes in an organism) has enabled rapid developments in the collection and analysis of various types of comprehensive molecular data such as transcriptomes (the complete set of gene expression data) and proteomes (the complete set of intracellular proteins). Fundamental omics research aims to link these omics data to molecular networks and pathways in order to advance the understanding of biological phenomena as systems at the molecular level.
Here at the RIKEN Omics Science Center, we are developing a versatile analysis system, called the "Life Science Accelerator (LSA)", with the objective of advancing omics research. LSA is a multi-purpose, large-scale analysis system that rapidly analyzes molecular networks. It collects various genome-wide data at high throughput from cells and other biological materials, comprehensively analyzes experimental data, and thereby aims to elucidate the molecular networks of the sample. The term "accelerator" was chosen to emphasize the strong supporting role that this system will play in supporting and accelerating life science research worldwide.
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