Image from Salk Institute
New research suggests the type of founder cell used to generate induced pluripotent stem cells (iPSCs) does not affect the iPSCs’ ability to differentiate into hematopoietic cells.
Instead, researchers found 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.
The team reported these findings in Cell Stem Cell.
The researchers assessed the hematopoietic differentiation capacities of 35 iPSC lines derived from 4 types of somatic tissues—human dermal fibroblasts, hematopoietic cells such as cord blood and peripheral blood, dental pulp cells, and keratinocytes—from 15 donors.
The team also assessed 4 embryonic stem cell lines in early phase and late phase.
The researchers found that hematopoietic commitment capacity was associated with expression of IGF2 in undifferentiated iPSCs, but not with type of founder cell.
Higher expression of IFG2 was indicative of iPSCs 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 iPSC DNA.
“DNA methylation has an effect on a cell staying pluripotent or differentiating,” explained study author Yoshinori Yoshida, MD, PhD, of the Center for iPS Cell Research and Application at Kyoto University in Japan.
The completion of differentiation correlated with less aberrant methylation during the reprogramming process.
Hematopoietic 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 iPSCs to the hematopoietic lineage.
Dr Yoshida and his colleagues said this research revealed molecular factors that can be used to evaluate the differentiation potential of different cell lines, which should expedite the progress of iPSCs to clinical use.
