Cell type of origin influences iPSC generation and differentiation to cells of the hematoendothelial lineage

Abstract

The use of induced pluripotent stem cells (iPSCs) as a source of cells for cell-based therapy in regenerative medicine is hampered by the limited efficiency and safety of the reprogramming procedure and the low efficiency of iPSC differentiation to specialized cell types. Evidence suggests that iPSCs retain an epigenetic memory of their parental cells with a possible influence on their differentiation capacity in vitro. We reprogramme three cell types, namely human umbilical cord vein endothelial cells (HUVECs), endothelial progenitor cells (EPCs) and human dermal fibroblasts (HDFs), to iPSCs and compare their hematoendothelial differentiation capacity. HUVECs and EPCs were at least two-fold more efficient in iPSC reprogramming than HDFs. Both HUVEC- and EPC-derived iPSCs exhibited high potentiality toward endothelial cell differentiation compared with HDF-derived iPSCs. However, only HUVEC-derived iPSCs showed efficient differentiation to hematopoietic stem/progenitor cells. Examination of DNA methylation at promoters of hematopoietic and endothelial genes revealed evidence for the existence of epigenetic memory at the endothelial genes but not the hematopoietic genes in iPSCs derived from HUVECs and EPCs indicating that epigenetic memory involves an endothelial differentiation bias. Our findings suggest that endothelial cells and EPCs are better sources for iPSC derivation regarding their reprogramming efficiency and that the somatic cell type used for iPSC generation toward specific cell lineage differentiation is of importance.

Exosomes Secreted from Induced Pluripotent Stem Cell-Derived Mesenchymal Stem Cells Accelerate Skin Cell Proliferation

“…For example, urinary cells would be an optimal for iPSC generation due to the relative easiness of cell acquisition [ 22 ]. On the other hand, selecting the optimal cell type for iPSC generation can be a critical issue because the differentiation potential of iPSCs can be affected by the origin of the donor cell [ 23 , 24 ]. We assume that exosomes from iMSCs originated from other somatic cells may have altered potential to those from MSCs used in this study, since the contents of exosomes are known to be changed by the cells from which they were produced.…”

Generation of Functional Cardiomyocytes from the Synoviocytes of Patients with Rheumatoid Arthritis via Induced Pluripotent Stem Cells

“…The reprogramming process can be affected by several factors, such as reprogramming methods and primary somatic cells 23 . The characteristics of the original cells can enhance or disturb reprogramming into iPSCs 24 25 . Synovial cells from RA patients are expected to undergo more epigenetic changes than other somatic cells.…”

Capturing Human Naïve Pluripotency in the Embryo and in the Dish

“…Some studies argued that such reprogramming errors resulted in differentiation bias toward their respective cell of origin lineage in mouse [142][143][144][145], human [146][147][148][149][150], and dog [151] iPSCs. It may be worth noting that most of these studies involved genome-integrating methods that introduced reprogramming factor transgenes through retroviral [142,[144][145][146][147]150,151] or lentiviral [148,149] vectors (including a lentiviral doxycycline-inducible secondary system [143]). Such viral reprogramming methods are now known to promote transcriptional and epigenetic errors [141] that were not detected using somatic cell nuclear transfer [141] or nonintegrative episomal derivation methods [119,120].…”