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Usui, T.

Publications and source records attributed to Usui, T..

2 recordsLinked to original sources

Expansion dynamics and marginal climates drive adaptation across geographic ranges

Every species experiences limits to its geographic distribution. Some evolutionary models predict that populations at range edges are less well-adapted to their local environments due to drift, expansion load, or swamping gene flow from the range interior. Alternatively, populations near range edges might be uniquely adapted to marginal environments. In this study, we use a database of transplant studies that quantify performance at broad geographic scales to test how local adaptation, site quality, and population quality change from spatial and climatic range centers towards edges. We find that populations from poleward edges perform relatively poorly, both on average across all sites (15% lower population quality) and when compared to other populations at home (31% relative fitness disadvantage), consistent with these populations harboring high genetic load. Populations from equatorial edges also perform poorly on average (18% lower population quality) but, in contrast, outperform foreign populations (16% relative fitness advantage), suggesting that populations from equatorial edges have strongly adapted to unique environments. Finally, we find that populations from sites that are thermally extreme relative to the species niche demonstrate strong local adaptation, regardless of their geographic position. Our findings indicate that both nonadaptive processes and adaptive evolution contribute to variation in adaptation across species ranges.

evolutionary biology

Progenitor identification and SARS-CoV-2 infection in long-term human distal lung organoid cultures

The distal lung contains terminal bronchioles and alveoli that facilitate gas exchange and is affected by disorders including interstitial lung disease, cancer, and SARS-CoV-2-associated COVID-19 pneumonia. Investigations of these localized pathologies have been hindered by a lack of 3D in vitro human distal lung culture systems. Further, human distal lung stem cell identification has been impaired by quiescence, anatomic divergence from mouse and lack of lineage tracing and clonogenic culture. Here, we developed robust feeder-free, chemically-defined culture of distal human lung progenitors as organoids derived clonally from single adult human alveolar epithelial type II (AT2) or KRT5+ basal cells. AT2 organoids exhibited AT1 transdifferentiation potential, while basal cell organoids progressively developed lumens lined by differentiated club and ciliated cells. Organoids consisting solely of club cells were not observed. Upon single cell RNA-sequencing (scRNA-seq), alveolar organoids were composed of proliferative AT2 cells; however, basal organoid KRT5+ cells contained a distinct ITGA6+ITGB4+ mitotic population whose proliferation segregated to a TNFRSF12Ahi subfraction. Clonogenic organoid growth was markedly enriched within the TNFRSF12Ahi subset of FACS-purified ITGA6+ITGB4+ basal cells from human lung or derivative organoids. In vivo, TNFRSF12A+ cells comprised ~10% of KRT5+ basal cells and resided in clusters within terminal bronchioles. To model COVID-19 distal lung disease, we everted the polarity of basal and alveolar organoids to rapidly relocate differentiated club and ciliated cells from the organoid lumen to the exterior surface, thus displaying the SARS-CoV-2 receptor ACE2 on the outwardly-facing apical aspect. Accordingly, basal and AT2 "apical-out" organoids were infected by SARS-CoV-2, identifying club cells as a novel target population. This long-term, feeder-free organoid culture of human distal lung alveolar and basal stem cells, coupled with single cell analysis, identifies unsuspected basal cell functional heterogeneity and exemplifies progenitor identification within a slowly proliferating human tissue. Further, our studies establish a facile in vitro organoid model for human distal lung infectious diseases including COVID-19-associated pneumonia.

cell biology