The primitive growth factor NME7AB induces mitochondrially active naïve-like pluripotent stem cells

Abstract

Naïve pluripotent stem cells (PSCs) display a distinctive phenotype when compared to their “primed” counterparts, including, but not limited to, increased potency to differentiate and more robust mitochondrial respiration. The cultivation and maintenance of naïve PSCs have been notoriously challenging, requiring the use of complex cytokine cocktails. NME7 AB is a newly discovered embryonic stem cell growth factor that is expressed exclusively in the first few days of human blastocyst development. It has been previously reported that growing primed induced PSCs (iPSCs) in bFGF-depleted medium with NME7 AB as the only added growth factor facilitates the regression of these cells to their naïve state. Here, we confirm this regression by demonstrating the reactivation of mitochondrial function in the induced naïve-like PSCs and increased ATP production in these cells, as compared to that in primed iPSCs.

Energy Metabolism Regulates Stem Cell Pluripotency

“…This study indicated that MTCH2 is important for elongated mitochondria which itself was sufficient for driving naïve-toprimed interconversion by altering histone deacetylation and nuclear gene reprogramming (Bahat et al, 2018). In addition, recent work has demonstrated that supplementation with a recombinant truncated human NME7 (NME7 AB ) is sufficient to induce a stable naïve-like state in hPSCs (Carter et al, 2016) associated with reactivation of mitochondrial function and stimulation of ATP production (O'Reilly et al, 2019).…”