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A Simple Yet Potent Trigger For Stem Cell Pluripotency

Feb 4, 2014 3:00:22 PM / by Maria

While generating induced Pluripotent Stem Cells (iPSCs) may have caused researchers some stress over the years, a new finding suggests that putting some stress on their cells instead could make their lives surprisingly easier. It turns out that external stressors like physical damage or low pH can lead a cell to have stem cell properties including pluripotency, making the process of cellular reprogramming faster and more efficient than ever before.

A mouse embryo injected with cells capable of stem cell properites like pluripotency through stress, tagged with a fluorescent protein. Mouse embryo injected with pluripotent GFP-tagged STAP cells. Image credit: Haruko Obokata.

The recently discovered phenomenon called Stimulus-Triggered Acquisition of Pluripotency (STAP) may allow scientists to easily reprogram cells into pluripotent stem cells for a variety of purposes. Obokata et al. found that different types of somatic cells could be used to generate these STAP cells when strong but unusual stimuli are introduced [1]. By uncovering this remarkable plasticity of differentiated somatic cells, this group has dramatically changed the game for stem cell researchers and the field of regenerative medicine.

Low pH Triggers Somatic Cell to Stem Cell Pluripotency Conversion

Showing that stimuli as simple as low pH, physical squeezing (trituration), and cell membrane damage (from a bacterial toxin) could all independently lead a cell toward pluripotency seems somewhat miraculous. Because the results were so unbelievable, Obokata et al. had a lot to prove. Purified lymphocytes were used first to demonstrate the incredible ability of a transient low pH to effectively generate STAP cells expressing pluripotency-related markers proteins and genes. Methylation was decreased at promoters of genes involved in cellular reprogramming, Oct4 and Nanog, suggesting that the epigenetic status at these genes was reprogrammed considerably within the treated cells. The pluripotent cells could also be differentiated into three-germ-layer derivatives and visceral endoderm-like epithelium. Other somatic cells that were successfully triggered into pluripotency (with varying efficiency) using low pH as a stimuli include those from tissues of the brain, fat, skin, bone marrow and more.

Embryos resulting from blastocysts injected with STAP cells show effective incorporation and contribution to chimeric embryos through germline transmission. The chimeric mice showed normal birth and development, with STAP cells contributing to all tissues examined, indicating that these pluripotent cells are able to successfully differentiate into germ-cell lineages in addition to all somatic-cell lineages in vivo.

The use of lymophocytes as the focus of this study is not surprising.  Hematopoietic cell lineages have been involved in many of the milestones of stem cell biology.  Hematopoietic cells are easily isolated in large numbers from patients and present ideal cell populations for manipulation.  At HemaCare, we've been collecting human blood samples for over 35 years.  We've refined collection and processing of hematopoietic cells for research and clinical applications.  We're excited to see this breakthrough and we've got the technology to support the advancement of applications in this area.  We provide a variety biological products for your research, including high quality human lymphocytes, making the generation of iPSCs even easier!

Although many questions remain about these STAP cells and stem cell pluripotency in general, this new approach will certainly help the field move towards answering them.

References:

[1] Obokata, H. et al. Nature 505, 641–647 (2014)

Topics: Assay Development, cellular reprogramming, iPSCs, lymphocytes, somatic cells, Stem Cells, Basic Research

Maria

Written by Maria

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