More of a good thing is not always better -- and certainly not if you are a stem cell

November 19, 2015

Stem cell research led by the Babraham Institute has uncovered key new knowledge about how placental stem cells switch between maintaining a stem cell identity to setting off down the route to becoming specialised cell types.

Intuitively, one would think that more of a good thing should be even better - specifically in the context of factors that maintain the self-renewing character of a stem cell. However, research from the Babraham Institute in association with the Centre for Trophoblast Research has found that this is certainly not the case for trophoblast stem cells from which the fundamental cell types of the placenta are derived. In looking at transcription factors - key orchestrators of the genes expressed in any given cell - the Babraham team observed that it is not simply their presence or absence that determines the stem cell state, but the finely tuned balance between them.

Two distinct populations of stem cells can be derived from the very early mammalian embryo; embryonic stem cells (ESC) which give rise to the embryo itself and their counterparts; trophoblast stem cells (TSCs) which give rise to major structures of the placenta.

In order to unpick the intricacies of the molecular mechanisms that underlie the self-renewal state of TSCs, the researchers used a multi-faceted approach looking at protein interactions, gene expression and genome binding. The researchers focused on three key transcription factors that they found interact physically with each other - Elf5, Eomes and Tfap2c. Each of these three factors is individually required to make a TSC. However, intriguingly, maintaining TSC identity did not simply depend on their sheer presence - it also critically depended on their relative abundance in proportion to each other. Thus, too much of Elf5 or Tfap2c in proportion to Eomes triggered TSCs to differentiate. The data reveal that the switch between retaining the self-renewing ability of TSCs and the onset of differentiation occurs when the triplet of transcription factors begins to operate as a duo.

Dr Myriam Hemberger, group leader in the Epigenetics programme at the Babraham Institute and senior author on the research paper published in Genes & Development said: "Our knowledge of the regulation of self-renewal and differentiation in trophoblast stem cells lags far behind that of ESCs yet this knowledge is critically important to better understand normal placental development - a prerequisite for embryo survival. Our insights reveal a role for Elf5 as a molecular switch governing the balance between TSC proliferation and differentiation, thereby explaining how the same transcription factors can drive different outcomes for the cell - simply by altering their relative abundance.

"At a practical level, our research explains why it is rather difficult to maintain mouse TSCs in culture and likely also why approaches to derive the same stem cell population from the human placenta have not been successful to date. Our work provides fundamental insights to facilitate that aim, a major goal that lies at the heart of our collaborative efforts with the Centre for Trophoblast Research".

Better understanding of how placental stem cells are regulated will help researchers to identify and obtain these cells from human placentas. These would be a fundamentally important research tool to provide a better understanding of the earliest stages in pregnancy when the foundations for a functional placenta are laid down; importantly, it is these early phases in development that - when abnormal - underlie the most common pregnancy complications.
This research was supported by the BBSRC, Centre for Trophoblast Research, University of Cambridge and the Wellcome Trust.

Babraham Institute

Related Stem Cells Articles from Brightsurf:

SUTD researchers create heart cells from stem cells using 3D printing
SUTD researchers 3D printed a micro-scaled physical device to demonstrate a new level of control in the directed differentiation of stem cells, enhancing the production of cardiomyocytes.

More selective elimination of leukemia stem cells and blood stem cells
Hematopoietic stem cells from a healthy donor can help patients suffering from acute leukemia.

Computer simulations visualize how DNA is recognized to convert cells into stem cells
Researchers of the Hubrecht Institute (KNAW - The Netherlands) and the Max Planck Institute in Münster (Germany) have revealed how an essential protein helps to activate genomic DNA during the conversion of regular adult human cells into stem cells.

First events in stem cells becoming specialized cells needed for organ development
Cell biologists at the University of Toronto shed light on the very first step stem cells go through to turn into the specialized cells that make up organs.

Surprising research result: All immature cells can develop into stem cells
New sensational study conducted at the University of Copenhagen disproves traditional knowledge of stem cell development.

The development of brain stem cells into new nerve cells and why this can lead to cancer
Stem cells are true Jacks-of-all-trades of our bodies, as they can turn into the many different cell types of all organs.

Healthy blood stem cells have as many DNA mutations as leukemic cells
Researchers from the Princess Máxima Center for Pediatric Oncology have shown that the number of mutations in healthy and leukemic blood stem cells does not differ.

New method grows brain cells from stem cells quickly and efficiently
Researchers at Lund University in Sweden have developed a faster method to generate functional brain cells, called astrocytes, from embryonic stem cells.

NUS researchers confine mature cells to turn them into stem cells
Recent research led by Professor G.V. Shivashankar of the Mechanobiology Institute at the National University of Singapore and the FIRC Institute of Molecular Oncology in Italy, has revealed that mature cells can be reprogrammed into re-deployable stem cells without direct genetic modification -- by confining them to a defined geometric space for an extended period of time.

Researchers develop a new method for turning skin cells into pluripotent stem cells
Researchers at the University of Helsinki, Finland, and Karolinska Institutet, Sweden, have for the first time succeeded in converting human skin cells into pluripotent stem cells by activating the cell's own genes.

Read More: Stem Cells News and Stem Cells Current Events is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to