Zoeb Jiwaji's research while affiliated with The University of Edinburgh and other places

... Astrocytes generated using the LSF protocol resemble morphologically mature astrocytes Despite having been neglected for decades, the key role of astrocytes in neurodegeneration has become increasingly evident [43]. To study astrocytic involvement in pathological mechanisms in more detail, disease modeling using iPSC-derived cultures has become a mainstream procedure. ...

... The astrocytic reaction to neurodegeneration can be assimilated to a medal: one face represents the pro-astrogliotic response that astrocytes can create through the production of cytokines, ROS or, more generally, of pro-inflammatory molecules; the opposite face, however, coincides with the attempt of these cells to produce neurotrophic factors, such as the brain-derived neurotrophic factor (BDNF), with the aim of protecting neurons from degeneration [25,26]. Therefore, we have on the one hand the development of a toxic Astrocytes and Aβ interaction. ...

... On DIV ~2, one-half of the medium was replaced with a growth medium containing the anti-mitotic cytosine arabinoside (Sigma-Aldrich) which restricts astrocytes and microglia to <0.01% (Hasel et al., 2018). Thereafter, the growth medium was replaced every other day. ...

... Moreover, a recent report suggested that current murine astrocyte differentiation protocols are unable to produce mature astrocytes 23 , in contrast to the thoroughly verified 20 human differentiation protocol analyzed above. Other groups have also revealed a similar lack of maturity in astrocytes differentiated without critical developmental cues from neurons 12,21 , underscoring the benefit of the mixed cell type cultures used in the human dataset and further emphasizing the need to understand cell fate decisions to better optimize murine glial differentiations. Starting from a serum-free astrocyte differentiation protocol 22 that produces immature astrocytes from mESCs, we developed a modified protocol aimed at producing CNS astrocytes ( Fig. 2a and Extended Data Fig. 6a). ...

... The blockade of CREB phosphorylation by CCL2 could also contribute to this. In fact, CREB has shown to modulate lactate production in cultured astrocytes [44]. Also, the reduced release of lactate may indicate that the ATP obtained from glycogenolysis is being used by astrocytes for other purposes such as the refill of their endoplasmic reticulum stores of Ca 2+ through sarco/endoplasmic reticulum Ca 2 -ATPase (SERCA) pumps [45], or to increased mitochondrial oxidative metabolism of pyruvate formed through glycolytic pathway. ...