Konstantinos-Dionysios Alysandratos's research while affiliated with University of Massachusetts Boston and other places

... To test whether activation of YAP signaling can promote iPSC-derived AEC2 differentiation, Burgess and colleagues used both genetic and pharmacological activation approaches. Indeed, these studies revealed that activation of YAP signaling was sufficient to induce AEC1 gene expression in iPSC-derived AEC2s (77). Such studies are still required to assess FSC-derived AEC2 potential in organoid cultures. ...

... While iPSC-derived AEC2s have the advantage of high throughput and scalability over AdSCs, the latter cells denote age-associated maturity and maintain genetic and epigenetic characteristics of the donor or patient lungs. Over the years, efforts have been made to comparatively assess the self-renewal, maturity, and differentiation capacity of iPSC-derived and primary AEC2s in ex vivo models (67,68). In the case of iPSC-derived AEC2s, inhibition of WNT signaling using XAV939 (tankyrase inhibitor) led to AEC1 differentiation (68,69). ...

... Importantly, early genetic diagnosis for rare variants causing ILD may help in prospectively stratifying LTx cohorts. Among the scientific community, great expectations for the future are the standardisation of the indications of genetic analysis, the enrolment of all SRG carriers in international registries, and the development of new pharmacological and gene-based therapies that could successfully restore dysfunction [27][28][29][30]. Until then, LTx remains the only "life-saving procedure" for those patients. ...

... iAT2s were then maintained in CKþDCI, feeding every two days, and in serially passaged every two weeks, as described. 29 Following single cell dissociation, iAT2s were maintained in CKþDCIþY-27632 for 3 days, then switched to CKþDCI media. Cell counts were taken from triplicate wells at each passage to calculate cell yield. ...

... To address these hurdles, we and others have applied induced pluripotent stem cell (iPSC)-derived type 2 alveolar epithelial cells (iAT2s) that provide an inexhaustible supply of disease-relevant cells. [23][24][25][26][27] iAT2s express lamellar bodies, overlap transcriptomically with primary human AT2s, recapitulate disease-specific phenotypes, and can be used to model environmental exposures. [23][24][25][26]28 We recently developed an inducible CRISPR interference (CRISPRi) iPSC system to interrogate the contribution of COPD GWAS genes to iAT2 function. ...

... However, to date, most organoid culture work, including those utilizing lung cells, have primarily utilized Matrigel ™ , a nonrelevant ECM derived from cancerous mouse tissue typically utilized for stem and cancer cell proliferation, and thus, an insufficient ECM to replicate the in situ human lung environment (Petrou et al., 2020). However, recent studies have highlighted the potential role of physiologically relevant ECM on type 2 alveolar epithelial cells (AT2) differentiation (Alysandratos et al., 2022;Nizamoglu et al., 2022;Sucre et al., 2022). As such, several groups have recently been decellularized lungs for hydrogel formation and cell culture (Hughes et al., 2010;Pouliot et al., 2016;De Hilster et al., 2020;Petrou et al., 2020;Pouliot et al., 2020;Uhl et al., 2020;Alysandratos et al., 2022;Nizamoglu et al., 2022;Marhuenda et al., 2022b;Saleh et al., 2022;Sucre et al., 2022). ...

... The mode of transmission has not yet been elucidated, but one study found LLOV in bat flies from infected bats, suggesting the potential role of ectoparasites in passive transmission of LLOV among bats [13]. Furthermore, the virus has been successfully isolated on multiple human cell lines, as well as human macrophages [13,16], highlighting the immense zoonotic potential of LLOV. The similarities between proteins VP24 and VP35 of both EBOV and LLOV are a further cause for concern because of their mode of inhibition of interferon responses in host cells, which inhibits innate immunity [17]. ...

... Consistently, native enhancers often contain sub-optimal motifs with reduced TF binding affinities 48,49 . Overall, these findings suggest that, although FOXA1 may use consensus motifs to engage with chromatin by itself, weaker motifs in conjunction with co-factors may play a more functional role during development to generate cell-type-specific binding and regulation 47,50 . ...

... While the current gold standard is to use air-liquid interface models for assaying CFTR activity, multiple groups have optimized forskolin-induced swelling assays using airway organoid cultures (83). Besides cystic fibrosis, lung organoid models have been used to study genetic mutations associated with other lung diseases including primary ciliary dyskinesia, Hermansky-Pudlak syndrome, and pediatric and adult interstitial lung diseases (28,49,59,61,78,81,82,120). Among AdSC-derived models, airway organoids are more commonly used than alveolar organoids to study disease pathogenesis. ...

... but the infection might not lead to disease, similar to the non-pathogenic Reston virus 21 . ...