| 11. |
- Asp, Michaela, et al.
(författare)
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A Spatiotemporal Organ-Wide Gene Expression and Cell Atlas of the Developing Human Heart
- 2019
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Ingår i: Cell. - : CELL PRESS. - 0092-8674 .- 1097-4172. ; 179:7, s. 1647-
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Tidskriftsartikel (refereegranskat)abstract
- The process of cardiac morphogenesis in humans is incompletely understood. Its full characterization requires a deep exploration of the organ-wide orchestration of gene expression with a single-cell spatial resolution. Here, we present a molecular approach that reveals the comprehensive transcriptional landscape of cell types populating the embryonic heart at three developmental stages and that maps cell-type-specific gene expression to specific anatomical domains. Spatial transcriptomics identified unique gene profiles that correspond to distinct anatomical regions in each developmental stage. Human embryonic cardiac cell types identified by single-cell RNA sequencing confirmed and enriched the spatial annotation of embryonic cardiac gene expression. In situ sequencing was then used to refine these results and create a spatial subcellular map for the three developmental phases. Finally, we generated a publicly available web resource of the human developing heart to facilitate future studies on human cardiogenesis.
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| 12. |
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| 13. |
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| 14. |
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| 15. |
- Baumgardt, Magnus, 1976-, et al.
(författare)
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Neuronal Subtype Specification within a Lineage by Opposing Temporal Feed-Forward Loops
- 2009
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Ingår i: Cell. - Cambridge,MA, USA : Cell Press. - 0092-8674 .- 1097-4172. ; 139:5, s. 969-982
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Tidskriftsartikel (refereegranskat)abstract
- Neural progenitors generate distinct cell types at different stages, but the mechanisms controlling these temporal transitions are poorly understood. In the Drosophila CNS, a cascade of transcription factors, the ‘temporal gene cascade’, has been identified, that acts to alter progenitor competence over time. However, many CNS lineages display broad temporal windows, and it is unclear how broad windows progress into sub-windows that generate unique cell types. We have addressed this issue in an identifiable Drosophila CNS lineage, and find that a broad castor temporal window is sub-divided by two different feed-forward loops, both of which are triggered by castor itself. The first loop acts to specify a unique cell fate, while the second loop suppresses the first loop, thereby allowing for the generation of alternate cell fates. This mechanism of temporal and ‘sub-temporal’ genes acting in opposing feed-forward loops may be used by many stem cell lineages to generate diversity.
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| 16. |
- Becher, Paul, et al.
(författare)
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A Conserved Dedicated Olfactory Circuit for Detecting Harmful Microbes in Drosophila
- 2012
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Ingår i: Cell. - : Elsevier BV. - 0092-8674 .- 1097-4172. ; 151, s. 1345-1357
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Tidskriftsartikel (refereegranskat)abstract
- Flies, like all animals, need to find suitable and safe food. Because the principal food source for Drosophila melanogaster is yeast growing on fermenting fruit, flies need to distinguish fruit with safe yeast from yeast covered with toxic microbes. We identify a functionally segregated olfactory circuit in flies that is activated exclusively by geosmin. This microbial odorant constitutes an ecologically relevant stimulus that alerts flies to the presence of harmful microbes. Geosmin activates only a single class of sensory neurons expressing the olfactory receptor Or56a. These neurons target the DA2 glomerulus and connect to projection neurons that respond exclusively to geosmin. Activation of DA2 is sufficient and necessary for aversion, overrides input from other olfactory pathways, and inhibits positive chemotaxis, oviposition, and feeding. The geosmin detection system is a conserved feature in the genus Drosophila that provides flies with a sensitive, specific means of identifying unsuitable feeding and breeding sites.
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| 17. |
- Bergmann, Olaf, et al.
(författare)
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Dynamics of Cell Generation and Turnover in the Human Heart.
- 2015
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Ingår i: Cell. - : Elsevier BV. - 1097-4172 .- 0092-8674. ; 161:7, s. 1566-1575
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Tidskriftsartikel (refereegranskat)abstract
- The contribution of cell generation to physiological heart growth and maintenance in humans has been difficult to establish and has remained controversial. We report that the full complement of cardiomyocytes is established perinataly and remains stable over the human lifespan, whereas the numbers of both endothelial and mesenchymal cells increase substantially from birth to early adulthood. Analysis of the integration of nuclear bomb test-derived (14)C revealed a high turnover rate of endothelial cells throughout life (>15% per year) and more limited renewal of mesenchymal cells (<4% per year in adulthood). Cardiomyocyte exchange is highest in early childhood and decreases gradually throughout life to <1% per year in adulthood, with similar turnover rates in the major subdivisions of the myocardium. We provide an integrated model of cell generation and turnover in the human heart. VIDEO ABSTRACT.
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| 18. |
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| 19. |
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| 20. |
- Billker, Oliver, et al.
(författare)
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Calcium and a calcium-dependent protein kinase regulate gamete formation and mosquito transmission in a malaria parasite
- 2004
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Ingår i: Cell. - : Elsevier. - 0092-8674 .- 1097-4172. ; 117:4, s. 503-514
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Tidskriftsartikel (refereegranskat)abstract
- Transmission of malaria parasites to mosquitoes is initiated by the obligatory sexual reproduction of the parasite within the mosquito bloodmeal. Differentiation of specialized transmission stages, the gametocytes, into male and female gametes is induced by a small mosquito molecule, xanthurenic acid (XA). Using a Plasmodium berghei strain expressing a bioluminescent calcium sensor, we show that XA triggers a rapid rise in cytosolic calcium specifically in gametocytes that is essential for their differentiation into gametes. A member of a family of plant-like calcium dependent protein kinases, CDPK4, is identified as the molecular switch that translates the XA-induced calcium signal into a cellular response by regulating cell cycle progression in the male gametocyte. CDPK4 is shown to be essential for the sexual reproduction and mosquito transmission of P. berghei. This study reveals an unexpected function for a plant-like signaling pathway in cell cycle regulation and life cycle progression of a malaria parasite.
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