Scientists develop very early stage human stem cell lines for first time

cjb250 — Fri, 04 Mar 2016 08:41:37 +0000

As well as a potential source of stem cells for use in regenerative medicine, the technique could open up new avenues of research into disorders such as Down’s syndrome.

̽��ֱ��ability to derive naïve stem cells has been possible for over thirty years from mouse embryos, using a technique developed by Sir Martin Evans and Professor Matthew Kaufman during their time at Cambridge, but this is the first time this has been possible from human embryos.

Human pluripotent stem cells for use in regenerative medicine or biomedical research come from two sources: embryonic stem cells, derived from fertilised egg cells discarded from IVF procedures; and induced pluripotent stem cells, where skin cells are reprogrammed to a pluripotent form. However, these cells are already “primed” for differentiation into specific cell types. In contrast, all instructions have been erased in naïve cells, which may make it easier to direct them into any cell type of interest.

Recently naïve-like human induced pluripotent stem cells have been created by reprogramming but it has been unknown whether they can also be obtained directly from the human embryo.

When an egg cell is fertilised by a sperm, it begins to divide and replicate before the embryo takes shape. Around day five, the embryonic cells cluster together and form a structure called the ‘blastocyst’. This occurs before implantation into the uterus. ̽��ֱ��blastocyst comprises three cell types: cells that will develop into the placenta and allow the embryo to attach to the womb; and cells that form the ‘yolk sac’, which provides nutrients to the developing foetus; and the ‘epiblast’ comprising the naïve cells that will develop into the future body.

In research published today in the journal Stem Cell Reports, scientists from the Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute managed to remove cells from the blastocyst at around day six and grow them individually in culture. By separating the cells, the researchers in effect stopped them ‘talking’ to each other, preventing them from being steered down a particular path of development.

“Until now it hasn’t been possible to isolate these naïve stem cells, even though we’ve had the technology to do it in mice for thirty years – leading some people to doubt it would be possible,” explains Ge Guo, the study’s first author, “but we’ve managed to extract the cells and grow them individually in culture. Naïve stem cells have many potential applications, from regenerative medicine to modelling human disorders.”

Naïve pluripotent stem cells in principle have no restrictions on the types of adult tissue into which they can develop, which means they may have promising therapeutic uses in regenerative medicine to treat devastating conditions that affect various organs and tissues, particularly those that have poor regenerative capacity, such as the heart, brain and pancreas.

Dr Jenny Nichols, joint senior author of the study, says that one of the most exciting applications of their new technique would be to study disorders that arise from cells that contain an abnormal number of chromosomes. Ordinarily, the body contains 23 pairs of identical chromosomes (22 pairs and one pair of sex chromosomes), but some children are born with additional copies, which can cause problems – for example, children with Down’s syndrome are born with three copies of chromosome 21.

“Even in many ‘normal’ early-stage embryos, we find several cells with an abnormal number of chromosomes,” explains Dr Nichols. “Because we can separate the cells and culture them individually, we could potentially generate ‘healthy’ and ‘affected’ cell lines. This would allow us to generate and compare tissues of two models, one ‘healthy’ and one that is genetically-identical other than the surplus chromosome. This could provide new insights into conditions such as Down’s syndrome.”

̽��ֱ��research was supported by the Medical Research Council, Biotechnology and Biological Sciences Research Council, Swiss National Science Foundation and the Wellcome Trust.

Reference
Guo, G et al. Naïve pluripotent stem cells derived directly from isolated cells of the human inner cell mass; Stem Cell Reports; e-pub 3 March 2015. DOI: 10.1016/j.stemcr.2016.02.005

Scientists at the ̽��ֱ�� of Cambridge have for the first time shown that it is possible to derive from a human embryo so-called ‘naïve’ pluripotent stem cells – one of the most flexible types of stem cell, which can develop into all human tissue other than the placenta.

Until now it hasn’t been possible to isolate human naïve stem cells, even though we’ve had the technology to do it in mice for thirty years – leading some people to doubt it would be possible

Ge Guo

Colonies of human naïve embryonic stem cells grown on mouse feeder cells

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Imaging the genome: cataloguing the fundamental processes of life

jfp40 — Mon, 27 Oct 2014 16:14:11 +0000

̽��ֱ��team of researchers, led by Dr Rafael Carazo Salas from the Department of Genetics, combined high-resolution 3D confocal microscopy and computer-automated analysis of the images to survey the fission yeast genome with respect to three key cellular processes simultaneously: cell shape, microtubule organisation and cell cycle progression. Microtubules are small, tube-like structures which help cells divide and give them their structure.

Of the 262 genes whose functions the team report in a study published today in the journal Developmental Cell, two-thirds are linked to these processes for the first time and a third are implicated in multiple processes.

“More than ten years since the publication of the human genome, the so-called ‘Book of Life’, we still have no direct evidence of the function played by half the genes across all species whose genomes have been sequenced,” explains Dr Carazo Salas. “We have no ‘catalogue’ of genes involved in cellular processes and their functions, yet these processes are fundamental to life. Understanding them better could eventually open up new avenues of research for medicines which target these processes, such as chemotherapy drugs.”

Using a multi-disciplinary strategy that took the team over four years to develop, the researchers were able to manipulate a single gene at a time in the fission yeast genome and see simultaneously how this affected the three cellular processes. Fission yeast is used as a model organism as it is a unicellular organism – in other words, it consists of just one cell – whereas most organisms are multicellular, yet many of its most fundamental genes carry out the same function in humans, for example in cell development.

̽��ֱ��technique enabled the researchers not only to identify the functions of hundreds of genes across the genome, but also, for the first time, to systematically ask how the processes might be linked. For example, they found in the yeast – and, importantly, validated in human cells – a previously unknown link between control of microtubule stability and the machinery that repairs damage to DNA. Many conventional cancer therapies target microtubular stability or DNA damage, and whilst there is evidence in the scientific literature that drugs targeting both processes might interact, the reason why has been unclear.

“Both the technique and the data it produces are likely to be a very valuable resource to the scientific community in the future,” adds Dr Carazo Salas. “It allows us to shine a light into the black box of the genome and learn exciting new information about the basic building blocks of life and the complex ways in which they interact.”

All the data from the study is being published online as an open resource for researchers to use. It will be available online at www.sysgro.org.

̽��ֱ��research was largely funded by the European Research Council, the Swiss Initiative in Systems Biology and the Swiss National Foundation.

A new study at the ̽��ֱ�� of Cambridge has allowed researchers to peer into unexplored regions of the genome and understand for the first time the role played by more than 250 genes key to cell growth and development.

It allows us to shine a light into the black box of the genome and learn exciting new information about the basic building blocks of life and the complex ways in which they interact.

Dr Rafael Carazo Salas

Image credit: L. Wagstaff, E. Piddini

Cells with damage in their DNA (green) assemble abnormally stable microtubule structures (purple to white). This new link between microtubule control and the response to DNA damage, originally discovered in yeast, can be observed also in human cells.

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̽��ֱ�� of Cambridge - Swiss National Foundation

Scientists develop very early stage human stem cell lines for first time

Imaging the genome: cataloguing the fundamental processes of life