You are here

| ESCs/iPSCs

DPPA5 Aids NANOG Protein in Human ESCs

Comment

Discuss

Review of “DPPA5 Supports Pluripotency and Reprogramming by Regulating NANOG Turnover” from Stem Cells by Stuart P. Atkinson

NANOG and DPPA5 are amongst the most well-known pluripotency associated factors; but while we have amassed a large body of data on the function of NANOG in human embryonic stem cells (ESCs), DPPA5’s role is less well understood [1]. Studies from the laboratory of Paul H. Krebsbach (Ann Arbor, Michigan, USA), which had sought to investigate effective feeder-free ESC growth substrate alternatives, found that DPPA5 expression increased when they employed a synthetic polymer coating known as PMEDSAH [2]. This suggested that DPPA5 may be important for maintaining pluripotency on such substrates and, in their new study published in Stem Cells, they now show that DPPA5 acts to stabilize and enhance the function of NANOG in human pluripotent stem cells (hPSCs) through direct interaction [3].

The author’s previous studies had found that hESCs grown on PMEDSAH (and other feeder-free substrates) induced higher levels of DPPA5 mRNA, while other pluripotency-associated factors remained unchanged. When they overexpressed DPPA5 in hESCs, NANOG protein levels dramatically increased suggesting the involvement of post-translational protein regulation. Further confocal (See Figure) and then co-immunoprecipitation experiments strongly suggested that DPPA5 interacted and stabilized the NANOG protein, which then acted to enhance the transcriptional function of NANOG and block neuroectodermal differentiation [4]. The authors also went on to discover that DPPA5 effectively synergized with OCT4, SOX2, KLF4, and C-MYC to enhance the generation of human induced pluripotent stem cells (hiPSCs).

For all those chem-heads out there PMEDSAH stands for poly[2-(methacryloyloxy) ethyl dimethyl-(3-sulfopropyl) ammonium hydroxide, and this exciting new ESC growth substrate has led to a new understanding of how DPPA5 aids the maintenance of pluripotency. This knowledge may also lead to the implementation of enhanced protocols for PSC maintenance and iPSC reprogramming and improved feeder- and xeno-free growth systems, which together may take us one step closer to the widespread clinical implementation of PSC-based therapeutics.

References

  1. Marynka-Kalmani K, Treves S, Yafee M, et al. The lamina propria of adult human oral mucosa harbors a novel stem cell population. Stem Cells 2010;28:984-995.
  2. Liu D, He XC, Qian P, et al. Leucine-rich repeat-containing G-protein-coupled Receptor 5 marks short-term hematopoietic stem and progenitor cells during mouse embryonic development. J Biol Chem 2014;289:23809-23816.
  3. Qian X, Kim JK, Tong W, et al. DPPA5 Supports Pluripotency and Reprogramming by Regulating NANOG Turnover. Stem Cells 2016;34:588-600.
  4. Vallier L, Mendjan S, Brown S, et al. Activin/Nodal signalling maintains pluripotency by controlling Nanog expression. Development 2009;136:1339-1349.