Current state of the opportunities for derivation of germ-like cells from pluripotent stem cells: are you a man, or a mouse?

Abstract

The concept of pluripotency as a prerogative of cells of early mammal embryos and cultured embryonic stem cells (ESC) has been invalidated with the advent of induced pluripotent stem cells. Later, it became clear that the ability to generate all cell types of the adult organism is also a questionable aspect of pluripotency, as there are cell types, such as germ cells, which are difficult to produce from pluripotent stem cells. Recently it has been proposed that there are at least two different states of pluripotency; namely, the naïve, or ground state, and the primed state, which may differ radically in terms of timeline of existence, signalling mechanisms, cell properties, capacity for differentiation into different cell types, etc. Germ-like male and female rodent cells have been successfully produced in vitro from ESC and induced pluripotent stem cells. The attempts to derive primate primordial germ cells (PGC) and germ cells in vitro from pluripotent stem cells, however, still have a low success rate, especially with the female germline. The paper reviews the properties of rodent and primate ESC with regard to their capacity for differentiation in vitro to germ-like cells, outlining the possible caveats to derivation of PGC and germ cells from primate and human pluripotent cells.

Human induced pluripotent stem cells and male infertility: an overview of current progress and perspectives

“…Recently, two developmentally and functionally distinct types of pluripotency have been defined: the naive state and the primed state ( Nichols and Smith, 2009 ; Petkova et al , 2014 ). First, cells in the naive state are competent to form blastocyst chimeras; the presence of two active X chromosomes is an epigenetic signature of naive pluripotecy; naive cells express KLF2 and KLF4 in addition to core pluripotency factors, and naive markers like reduced expression 1 (REX1, officially known as ZFP42), nuclear receptor subfamily 0 group B member 1 (NR0B1) and fibroblast growth factor 4 (FGF4); the two types of pluripotent cells also respond differently to signal molecules, such as leukemia inhibitory factor/signal transducer and activator of transcription 3 (LIF/STAT3) and fibroblast growth factor/extracellular regulated kinase (FGF/ERK); more specifically, the differentiation potential of primed pluripotent cells into PGCs and mature germ cells is drastically different from that of naive pluripotent cells ( Arabadjiev et al , 2012 ; De Los Angeles et al , 2012 ; Nichols and Smith, 2009 , 2011 ).…”

Small molecules and human cardiomyogenesis: Is there a bottleneck in current research?

“…Moreover, the use of both murine and human stem cell lines in the same experiment promises a faster generation of data about the stem cell biology of the two species. There have been reports that despite the apparent closeness of the two species, there are some essential differences on molecular level that show greatly in their capacity for maintenance of the undifferentiated state and targeting into differentiation into different cell types [25]. The report of Kattmanet et al [26] about the stage-specific optimization of Activin/Nodal and BMP signaling promoting cardiac differentiation of mouse and human pluripotent stem cell lines is an excellent example of multi-testbed-based research.…”

Human pluripotent stem-cell-derived cardiomyocytes in cardiovascular drug discovery and development

“…The intriguing and exciting prospects for stem cells with properties of self-renewal, clonogeneticity, and multi-potentiality, have been hailed for many years to offer enormous potential in the study of disease and have generated great expectations in relation to possible applications [6,[12][13][14]. Innovative research in the field of medical and pharmaceutical biotechnology has led to the ability to derive both human embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs) by differentiating embryonic blastocysts and reprogramming adult fibroblasts, respectively.…”