Insulin-producing beta cells from stem cells: Scientists decipher early molecular mechanisms of differentiation

Jan 23, 2014
Insulin-Producing Beta Cells from Stem Cells: Scientists Decipher Early Molecular Mechanisms of Differentiation
Endodermal cells, they form organs such as lung, liver and pancreas. Credit: IDR, Helmholtz Zentrum München

The Wnt/β-catenin signaling pathway and microRNA 335 are instrumental in helping form differentiated progenitor cells from stem cells. These are organized in germ layers and are thus the origin of different tissue types, including the pancreas and its insulin-producing beta cells. With these findings, Helmholtz Zentrum München scientists have discovered key molecular functions of stem cell differentiation which could be used for beta cell replacement therapy in diabetes. The results of the two studies were published in the renowned journal Development.

The findings of the scientists of the Institute of Diabetes and Regeneration Research (IDR) at Helmholtz Zentrum München (HMGU) provide new insights into the molecular regulation of . These results reveal important target structures for regenerative therapy approaches to chronic diseases such as diabetes.

During embryonic development, organ-specific cell types are formed from pluripotent , which can differentiate into all cell types of the human body. The pluripotent cells of the embryo organize themselves at an early stage in germ layers: the endoderm, mesoderm and ectoderm. From these three cell populations different functional arise, such as , , and specific organ cells.

Various signaling pathways are important for this germ layer organization, including the Wnt/β-catenin signaling pathway. The cells of the pancreas, such as the beta cells, originate from the endoderm, the germ layer from which the gastrointestinal tract, the liver and the lungs also arise. Professor Heiko Lickert, director of the IDR, in collaboration with Professor Gunnar Schotta of LMU München, showed that the Wnt/β-catenin signaling pathway regulates Sox17, which in turn regulates molecular programs that assign to the endoderm, thus inducing an initial differentiation of the stem cells.

In another project Professor Lickert and his colleague Professor Fabian Theis, director of the Institute of Computational Biology (ICB) at Helmholtz Zentrum München, discovered an additional mechanism that influences the progenitor cells. miRNA-335, a messenger nucleic acid, regulates the endodermal transcription factors Sox17 and Foxa2 and is essential for the differentiation of cells within this germ layer and their demarcation from the adjacent mesoderm. The concentrations of the transcription factors determine here whether these cells develop into lung, liver or . To achieve these results, the scientists combined their expertise in experimental research with mathematical modeling.

"Our findings represent two key processes of stem ," said Lickert. "With an improved understanding of cell formation we can succeed in generating functional specialized cells from stem cells. These could be used for a variety of therapeutic approaches. In diabetes, we may be able to replace the defective beta cells, but regenerative medicine also offers new therapeutic options for other organ defects and diseases."

Diabetes is characterized by a dysfunction of the insulin-producing beta cells of the pancreas. Regenerative treatment approaches aim to renew or replace these cells. An EU-funded research project ('HumEn'), in which Lickert and his team are participating, shall provide further insights in the field of beta-cell replacement therapy.

The aim of research at Helmholtz Zentrum München, a partner in the German Center for Diabetes Research (DZD), is to develop new approaches for the diagnosis, treatment and prevention of major common diseases such as diabetes mellitus.

Explore further: Stem cells on the road to specialization

More information: Engert, S. et al. (2013). "Wnt/β-catenin signalling regulates Sox17 expression and is essential for organizer and endoderm formation in the mouse," Development, DOI: 10.1242/dev.088765

Yang, D. et al. (2014, epub ahead of print). "miR-335 promotes mesendodermal lineage segregation and shapes a transcription factor gradient in the endoderm," Development, DOI: 10.1242/dev.104232

Related Stories

Stem cells on the road to specialization

Jan 07, 2014

Scientists at the University of Copenhagen have gained new insight into how both early embryonic cells and embryonic stem cells are directed into becoming specialised cell types, like pancreatic and liver ...

Study reveals how to better master stem cells' fate

Oct 24, 2013

(Phys.org) —USC scientist Qi-Long Ying and a team of researchers have long been searching for biotech's version of the fountain of youth—ways to encourage embryonic stem cells (ESCs) and epiblast stem ...

Pancreatic stem cells isolated from mice

Sep 17, 2013

Scientists have succeeded in growing stem cells that have the ability to develop into two different types of cells that make up a healthy pancreas. The research team led by Dr. Hans Clevers of the Hubrecht Institute, The ...

A step closer to muscle regeneration

Dec 10, 2013

(Medical Xpress)—Muscle cell therapy to treat some degenerative diseases, including Muscular Dystrophy, could be a more realistic clinical possibility, now that scientists have found a way to isolate muscle cells from embryonic ...

Recommended for you

Sugar mimics guide stem cells toward neural fate

17 hours ago

Embryonic stem cells can develop into a multitude of cells types. Researchers would like to understand how to channel that development into the specific types of mature cells that make up the organs and other structures of ...

Researchers uncover secrets of internal cell fine-tuning

Jul 29, 2014

New research from scientists at the University of Kent has shown for the first time how the structures inside cells are regulated – a breakthrough that could have a major impact on cancer therapy development.

User comments : 1

Adjust slider to filter visible comments by rank

Display comments: newest first

DanPoynter
not rated yet Jan 26, 2014
CANCER? BLOOD DISORDER?
A stem cell transplant could be the life-saving answer.

New book:
TRANSPLANT HANDBOOK FOR PATIENTS: Replacing Stem Cells in Your Bone #Marrow.

This book helps the patient, caregiver, and family to understand the #stem cell #transplant journey.

By a 75-year old author, at 6 months since his transplant, who is setting records for recovery.
http://TransplantHandbook.com