publications
2021
Cimino, I. et al. ‘Activation of the hypothalamic–pituitary–adrenal axis by exogenous and endogenous GDF15’. PNAS, 118, 27 (2021). doi: 10.1038/s42003-021-02453-y.
From the lab of Stephen O’Rahilly, University of Cambridge
From the lab of Anthony Davenport, University of Cambridge
From the lab of Austin Smith, University of Cambridge & University of Exeter
In the study of embryonic stem cells, stem cells representative of naïve and primed pluripotency have been well established in the forms of embryonic stem cells (ESCs) and epiblast-derived stem cells (EpiSCs). In this study Kinoshita et al. fill the gap between early and late pluripotency in describing an intermediate state; formative stem (FS) cells. FS cells differ from both ESCs and EpiSCs, a difference beautifully exemplified by their relative contribution to chimeras. Compared with ESCs, which readily contribute to chimeras, FS chimera contribution is less frequent, and their contribution is less evenly distributed. EpiSCs on the other hand do not generally contribute to chimeras at all. FS cells were established by culturing E5.5 epiblasts, or ES cells, in N2B27 media supplemented with a low dose of Qkine Activin A alongside a Wnt inhibitor and pan-retinoic acid receptor inverse agonist. We are proud our growth factors could be part of such an exciting finding!
Masaki Kinoshita, first author, MRC Cambridge Stem Cell Institute, University of Cambridge, says:
“Formative” pluripotency exists transiently in early development and naive mouse ES cell differentiation, which cells directly respond to differentiation signals. This paper showed that formative pluripotency is now captured in culture and expands its knowledge including chimaera competency of early embryonic cells.
In embryonic development, growth factors are delivered in a highly controlled and targeted manner, however when differentiating iPSCs the real challenge is to effectively mimic these conditions. Consequently, iPSC differentiation is plagued by issues such as low efficiency and a lack of homogeneity. In their recent paper Andreasson et al. take a step towards improving the differentiation of iPSCs to definitive endoderm. The group employs gold nanoparticles to generate a gradient of immobilised Activin A – a member of the TGF-β superfamily that plays a key role in definitive endoderm development. Using this gradient, the group was able to deliver Activin A in a controlled and localised manor, resulting in more efficient differentiation. By deploying their innovative approach, the group observed a dose dependent response of the cells to Activin A, as defined by expression of differentiation markers SOX17 and GATA4. Their results indicate that it may be possible to define an optimal density of Activin A for definitive endoderm differentiation – a finding that could improve the homogeneity and speed of differentiation. This innovative study is a wonderful example of how reconsidering the way in which growth factors are delivered can lead to advances in our understanding of the precise control of stem cell differentiation and how these cells undertake their fate decisions.
2020
Borkowska, M. & Leitch, H. G. Mouse Primordial Germ Cells: In Vitro Culture and Conversion to Pluripotent Stem Cell Lines. Methods Mol Biol 2214, 59–73 (2021). doi: 10.1007/978-1-0716-0958-3_5
From the lab of Harry Leitch, Imperial College London
From the lab of Graziano Martello, University of Padua
From the lab of Harry Leitch, Imperial College London
2019
From the lab of José Silva, University of Cambridge
reviewers comments available to view: Stadtfeld, M. Evaluation of Stuart et al.: Distinct Molecular Trajectories Converge to Induce Naive Pluripotency. Cell Stem Cell 25, 297–298 (2019). doi: 10.1016/j.stem.2019.08.009
2018
From the lab of Tamir Rashid, Kings College London
