Proteomic Analysis of Mouse Oocytes Identifies PRMT7 as a Reprogramming Factor that Replaces SOX2 in the Induction of Pluripotent Stem Cells

The
reprogramming process that leads to induced pluripotent stem
cells (iPSCs) may benefit from adding oocyte factors to Yamanaka’s
reprogramming cocktail (OCT4, SOX2, KLF4, with or without MYC; OSK­(M)).
We previously searched for such facilitators of reprogramming (the
reprogrammome) by applying label-free LC–MS/MS analysis to
mouse oocytes, producing a catalog of 28 candidates that are (i) able
to robustly access the cell nucleus and (ii) shared between mature
mouse oocytes and pluripotent embryonic stem cells. In the present
study, we hypothesized that our 28 reprogrammome candidates would
also be (iii) abundant in mature oocytes, (iv) depleted after the
oocyte-to-embryo transition, and (v) able to potentiate or replace
the OSKM factors. Using LC–MS/MS and isotopic labeling methods,
we found that the abundance profiles of the 28 proteins were below
those of known oocyte-specific and housekeeping proteins. Of the 28
proteins, only arginine methyltransferase 7 (PRMT7) changed substantially
during mouse embryogenesis and promoted the conversion of mouse fibroblasts
into iPSCs. Specifically, PRMT7 replaced SOX2 in a factor-substitution
assay, yielding iPSCs. These findings exemplify how proteomics can
be used to prioritize the functional analysis of reprogrammome candidates.
The LC–MS/MS data are available via ProteomeXchange with identifier
PXD003093.