Magnetotactic bacteria possess organelles called magnetosomes that confer a magnetic moment on the cells, resulting in their partial alignment with external magnetic fields. Here we show that analysis of the trajectories of cells exposed to an external magnetic field can be used to measure the average magnetic dipole moment of a cell population in at least five different ways. We apply this analysis to movies of Magnetospirillum magneticum AMB-1 cells, and compare the values of the magnetic moment obtained in this way to that obtained by direct measurements of magnetosome dimension from electron micrographs. We find that methods relying on the viscous relaxation of the cell orientation give results comparable to that obtained by magnetosome measurements, whereas methods relying on statistical mechanics assumptions give systematically lower values of the magnetic moment. Since the observed distribution of magnetic moments in the population is not sufficient to explain this discrepancy, our results suggest that non-thermal random noise is present in the system, implying that a magnetotactic bacterial population should not be considered as similar to a paramagnetic material.
SummaryIntestinal organoids derived from human pluripotent stem cells (hPSCs) are valuable in vitro research models that enable simplified access to human gastrointestinal tissues. Here, we report the in vitro generation of enterospheres (hEnS) from hPSC-derived gastrointestinal epithelial precursors. hEnS are cystic spheroids with a simple uniform structure composed entirely of intestinal epithelium. hEnS express markers of mature brush border cells and share a transcriptome profile similar to that of more mature intestinal organoids. Modulation of signaling cues enables control of hEnS growth and differentiation, including long-term propagation. We show that hEnS can be exploited for functional studies: hEnS display an innate immune response when treated with enteric pathogens, and transgenic modification of hEnS with a fluorescence cell-cycle reporter enables hEnS-forming stem cell enrichment. Our work establishes hEnS as an accessible and tractable in vitro modeling system for studying human gastrointestinal biology.
Maturation of the intestinal epithelium is a necessary step for development of a fully functioning gastrointestinal tract. Studies of rodent gastrointestinal development and maturation have long been used to guide understanding of human intestinal maturation, in part because accessing human gestational stage intestinal tissues to perform equivalent human studies can be difficult. Notable differences have already been described in the timing of key stages in intestinal development between rodents and humans, but the conservation of intestinal maturation events between the two species is poorly understood. We hypothesized that species-related differences in intestinal development would alter the timing of key maturation events between human and mouse. We tested our hypothesis by performing a detailed comparison of hallmarks of intestinal maturation in human and mouse gestational intestine, including markers that describe the emergence of intestinal cell types, functionality and structural integrity. Our study demonstrates clear timing differences between maturation stages in mouse and human, with the majority of human maturation hallmarks acquired post-partum, in contrast to their gestational emergence in mouse. Our work suggests caution when translating murine intestinal maturation observations to the human, and provides a maturation road map that will be helpful to those seeking to produce mature intestine from in vitro stem cell sources.
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