Ground-breaking study provides scientists with a critical new understanding of stem cell development

Written by Elena Conroy

UCLA researchers develop pioneering method to define the different stages of stem cell reprogramming.

UCLA researchers at the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research (LA, USA) established a first-of-its-kind methodology that defines the unique stages by which specialized cells are reprogrammed into induced Pluripotent Stem Cells (iPSC). The study was recently published in Cell.

Reprogramming a cell is a long process and largely inefficient, with typically less than one percent of the primary skin or blood cells successfully completing the journey to becoming an iPSC. The exact stages a cell goes through during the reprogramming process is poorly understood. However, uncovering the mechanisms of the process is essential, as iPSCs hold great promise in the field of regenerative medicine. “This research has broad impact, because by deepening our understanding of cell reprogramming we have the potential to improve disease modeling and the generation of better sources of patient-specific specialized cells suitable for replacement therapy,” explained Plath, professor of biological chemistry at the Center. “This can ultimately benefit patients with new and better treatments for a wide range of diseases.”

The research team developed a roadmap of the reprogramming process using detailed time-course analyses. They induced the reprogramming of skin cells into iPSC, then observed and analyzed the process of transformation at the single-cell level. Plath’s team found that the changes that happen in cells during reprogramming occur in a sequential stage-by-stage manner, and that these stages were the same across all the different reprogramming systems and different cell types analyzed.

“The exact stage of reprogramming of any cell can now be determined,” explained Vincent Pasque from the Plath group. “This study signals a big change in thinking, because it provides simple and efficient tools for scientists to study stem cell creation in a stage-by-stage manner. Most studies to date ignore the stages of reprogramming, but we can now seek to better understand the entire process on both a macro and micro level.”

Plath’s team further discovered that the stages of reprogramming are not simply the reversed sequence of stages of embryo development as some resist a change until late during reprogramming to iPSCs.

“This reflects how cells do not like to change from one specialized cell type to another and resist a change in cell identity,” stated Pasque. “Resistance to reprogramming also helps to explain why reprogramming takes place only in a very small proportion of the starting cells.”

Plath’s group plans future studies to actively isolate specific cell types during specific stages of reprogramming and hope the research will encourage further investigation into the characteristics of iPSC development.


Pasque V, Tchieu J, Karnik R et al. X Chromosome Reactivation Dynamics Reveal Stages of Reprogramming to Pluripotency. Cell, 159 (7) , 1681 — 1697 doi: [Epubahead of print] (2015); UCLA Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research press release: