Nav: Home

Original cell type does not affect iPS cell differentiation to blood

July 28, 2016

Cell reprogramming involves making one cell type into another. In theory, all cells can be reprogrammed, but there is evidence that the original cell (founder cell) influences the type of cell to which it can be reprogrammed. In general, founder cells are easy to acquire from a donor and come in one of four types: fibroblasts, keratinocytes, peripheral and umbilical cord blood, and dental pulp cells. Labs from around the world have made iPS cell lines using different founder cells. The potential influence of founder cells is profound for regenerative medicine and other medical applications, since they suggest that the cell line should be selected based on the desired cell type.

Another factor that could also contribute to the efficiency of iPS cell line differentiation is the method with which the iPS cells were made. Many methods are used, but the most common, according to Associate Professor Yoshinori Yoshida at CiRA are "retrovirus, episomal plasmids and Sendai virus."

Blood describes a diverse group of cells that includes those that carry oxygen, heal wounds, and fight off infection, and the production of clinical grade blood has remained a major goal of reprogramming science. Some scientists have argued that to acquire hematopoietic cells, the best founder cells are coincidently hematopoietic cells. To investigate the contribution of founder cells in cell differentiation to hematopoietic cells, the Yoshida lab investigated an unprecedented number of iPS cell lines made using all of the above founder cells and reprogramming methods. .

Interestingly, the group found neither of these factors has a significant effect. Instead, they show the expression of certain genes and DNA methylations were better indicators of the efficiency at which a cell line could be differentiated into the hematopoietic lineage. "We found the IFG2 gene marks the beginning of reprogramming to hematopoietic cells", said Dr. Masatoshi Nishizawa, a hematologist in the Yoshida lab and first author of the new study. The researchers show that higher expression of the growth hormone IFG2, or insulin-like growth factor 2, is indicative of iPS cells initiating their conversion into hematopoietic cells. Even though IFG2 itself is not directly related to hematopoiesis, its uptake corresponded to an increase in the expression of genes that are.

Although IFG2 marked the beginnings of differentiation to hematopoietic lineage, the completion of differentiation was marked by the methylation profiles of the iPS cell DNA. "DNA methylation has an effect on a cell staying pluripotent or differentiating," explained Associate Professor Yoshida. The completion of differentiation correlated with less aberrant methylation during the reprogramming process. Blood founder cells showed a much lower propensity for aberrant methylation than did other founder cells, which could explain why in the past scientists attributed the founder cell to the effectiveness of differentiating iPS cells to the hematopoietic lineage.

These findings reveal molecular factors that can be used to evaluate the differentiation potential of different cell lines, which should expedite the progress of iPS cells to clinical use. Nishizawa expects this work to act as a basis to evaluate cell lines for the preparation of other cell types. "I think each cell type will have its own special patterns," he said.
-end-


Center for iPS Cell Research and Application - Kyoto University

Related Genes Articles:

Insomnia genes found
An international team of researchers has found, for the first time, seven risk genes for insomnia.
Genes affecting our communication skills relate to genes for psychiatric disorder
By screening thousands of individuals, an international team led by researchers of the Max Planck Institute for Psycholinguistics, the University of Bristol, the Broad Institute and the iPSYCH consortium has provided new insights into the relationship between genes that confer risk for autism or schizophrenia and genes that influence our ability to communicate during the course of development.
The fate of Neanderthal genes
The Neanderthals disappeared about 30,000 years ago, but little pieces of them live on in the form of DNA sequences scattered through the modern human genome.
Face shape is in the genes
Many of the characteristics that make up a person's face, such as nose size and face width, stem from specific genetic variations, reports John Shaffer of the University of Pittsburgh in Pennsylvania, and colleagues, in a study published on Aug.
Study finds hundreds of genes and genetic codes that regulate genes tied to alcoholism
Using rats carefully bred to either drink large amounts of alcohol or to spurn it, researchers at Indiana and Purdue universities have identified hundreds of genes that appear to play a role in increasing the desire to drink alcohol.
Reading between the genes
For a long time dismissed as 'junk DNA,' we now know that also the regions between the genes fulfill vital functions.
The silence of the genes
Research led by Dr. Keiji Tanimoto from the University of Tsukuba, Japan, has brought us closer to understanding the mechanisms underlying the phenomenon of genomic imprinting.
Why some genes are highly expressed
The DNA in our cells is folded into millions of small packets, like beads on a string, allowing our two-meter linear DNA genomes to fit into a nucleus of only about 0.01 mm in diameter.
Activating genes on demand
A new approach developed by Harvard geneticist George Church, Ph.D., can help uncover how tandem gene circuits dictate life processes, such as the healthy development of tissue or the triggering of a particular disease, and can also be used for directing precision stem cell differentiation for regenerative medicine and growing organ transplants.
Controlling genes with light
Researchers at Duke University have demonstrated a new way to activate genes with light, allowing precisely controlled and targeted genetic studies and applications.

Related Genes Reading:

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Digital Manipulation
Technology has reshaped our lives in amazing ways. But at what cost? This hour, TED speakers reveal how what we see, read, believe — even how we vote — can be manipulated by the technology we use. Guests include journalist Carole Cadwalladr, consumer advocate Finn Myrstad, writer and marketing professor Scott Galloway, behavioral designer Nir Eyal, and computer graphics researcher Doug Roble.
Now Playing: Science for the People

#529 Do You Really Want to Find Out Who's Your Daddy?
At least some of you by now have probably spit into a tube and mailed it off to find out who your closest relatives are, where you might be from, and what terrible diseases might await you. But what exactly did you find out? And what did you give away? In this live panel at Awesome Con we bring in science writer Tina Saey to talk about all her DNA testing, and bioethicist Debra Mathews, to determine whether Tina should have done it at all. Related links: What FamilyTreeDNA sharing genetic data with police means for you Crime solvers embraced...