Changes in cell populations during epithelium restitution.

<p>The transit amplifying population will transiently expand during epithelium restitution. In the case of extreme tissue lesion where more than 90% tissue is damaged, there will be an overwhelming response of the crypt-villus system and the transit amplifying population will expand in an uncontrolled manner, producing intestinal hyperplasia or adenoma in the teleost and murine intestines, though it seems less likely in human intestine. Denotation: ▾ for zebrafish; • for mouse; ▪ for human.</p

The paradigm of epithelium renewal in the intestine.

<p>(A) Cell proliferation and apoptosis in the intestine of zebrafish. Left panel: Cell proliferation assay with proliferating cells stained dark brown. Middle panel: Cell apoptosis assay with apoptotic cells stained green. Right panel: Compartmentalization of epithelium into stem cells, transit amplifying cells, differentiated cells and apoptotic cells. (B) The intestinal epithelium is divided into four components while constructing the model, based on the analogous paradigm of epithelium renewal across teleost, murine and human species. Stem cells maintain their own population through self-renewal, and in the mean time, they produce progenies that will differentiate later on. Transit amplifying cells are directly derived from stem cells and go through rapid expansion. Then they go for cell differentiation and finally apoptosis. Denotation: - population of stem cells; - population of transit amplifying cells; - population of differentiated cells. Note that all populations are normalized against their homeostatic populations in the model.</p

Stem cell number in the small intestine of different species as suggested by <i>STORM</i> model.

<p>Stem cell number in the small intestine of different species as suggested by <i>STORM</i> model.</p

General relationships between , and .

<p>(A) In general, is positively correlated with . For teleosts where is smaller, is lower; For humans where is bigger, is higher. (B) The epithelium renewal cycle is also correlated to the value of . Bigger value of means longer renewal cycle. Cycles are normalized to be dimensionless. : dividing frequencystem population/transit amplifying population; : intestinal epithelium renewal cycle; : ratio of differentiated epithelium population/transit amplifying population.</p

Schematic illustration of the STORM model.

<p>The model takes experimental measurement of transit amplifying and differentiated cell populations as input information. By optimizing the turnover dynamics, it yields the number of stem cells required on each section of pocket or crypt of the intestine. It also provides information on epithelium turnover changes, for example, extended turnover cycles due to a reduction in the transit amplifying cells.</p

Mapping Resolution.

<p>(<b>A</b>). <b>Using a top random mapping strategy to classify at the strain or genus level.</b> This image shows the mapping fate of all 22,735,802 mock queries when mapped to the RGD under a top random mapping strategy, falling back to genus level annotations when the strain cannot be identified. (<b>B</b>). <b>Using a unique only mapping strategy to classify at the strain or genus level.</b> This image shows the mapping fate of all 22,735,802 mock queries when mapped to the RGD under a unique only mapping strategy, falling back to genus level annotations when the strain cannot be identified. (<b>C</b>). <b>Using a top random mapping strategy to classify at the strain or species level.</b> This image shows the mapping fate of all 22,735,802 mock queries when mapped to the RGD under a top random mapping strategy, falling back to species level annotations when the strain cannot be identified. (<b>D</b>). <b>Using a unique only mapping strategy to classify at the strain or species level.</b> This image shows the mapping fate of all 22,735,802 mock queries when mapped to the RGD under a unique only mapping strategy, falling back to species level annotations when the strain cannot be identified.</p

The effect of strain representation within the RGD and mapping strategy on mapping resolution.

<p>(<b>A</b>). <b>Top 20 most covered strains from the genus </b><b><i>Bacillus</i></b><b> found in mock vs. RGD mapping.</b> This figure shows the detected coverage using both mapping strategies when aligning the mock community queries against the full RGD for <i>Bacillus</i> strains. Note that the strain present in the mock community (<i>B. cereus ATCC 10987</i>) is indicated in the image. (<b>B</b>). <b>Top 20 most covered strains from the genus </b><b><i>Clostridium</i></b><b> found in mock vs. RGD mapping.</b> This figure shows the detected coverage using both mapping strategies when aligning the mock community queries against the full RGD for <i>Clostridium</i> strains. Note that the strain present in the mock community (<i>C. beijerinckii NCIMB 8052</i>) is indicated in the image. (<b>C</b>). <b>Top 20 most covered strains from the genus </b><b><i>Bacteroides</i></b><b> found in mock vs. RGD mapping.</b> This figure shows the detected coverage using both mapping strategies when aligning the mock community queries against the full RGD for <i>Bacteroides</i> strains. Note that the strain present in the mock community (<i>B. vulgatus ATCC 8482</i>) is indicated in the image. (<b>D</b>). <b>Top 20 most covered strains from the genus </b><b><i>Escherichia</i></b><b> found in mock vs. RGD mapping.</b> This figure shows the detected coverage using both mapping strategies when aligning the mock community queries against the full RGD for <i>Escherichia</i> strains. Note that the strain present in the mock community (<i>E. coli K-12 MG1655</i>) is indicated in the image.</p

Amended strain similarity to original MMD strains.

*<p>For <i>Streptococcus</i>, 2 of the 3 strains were removed, leaving only S.mutans UA159.</p

Chi-square comparison of detected abundances^*.

*<p>Based on depth of coverage per genome. Values > = 0.05 are considered significantly similar.</p

Mock strain coverage.

<p>(<b>A</b>). <b>Coverage of mock strains in the MMD.</b> This image shows the results of mapping the mock community query against the MMD under both top random and unique only mapping strategies. (<b>B</b>). <b>Coverage of mock strains in the RGD.</b> This image shows the results of mapping the mock community query against the RGD under both top random and unique only mapping strategies. The numbers printed in the plot reflect the number of strains present in the RGD for the genus in which the displayed strain belongs.</p