* Development of intestinal organoids as tissue surrogates: cell composition and the epigenetic control of differentiation.
- Intestinal organoids are multicellular crypt-like structures that can be derived from adult intestinal stem cells (ISCs), embryonic stem cells (ESCs) or induced pluripotent stem cells (IPSCs). Here we show that intestinal organoids generated from mouse ESCs were enriched in ISCs and early progenitors. Treatment of these organoids with a γ-secretase inhibitor increased Math1 and decreased Hes1 expression, indicating Notch signaling regulates ISC differentiation in these organoids. Lgr5 and Tert positive ISCs constituted approximately 10% and 20% of the organoids. As found in native tissue, Lgr5 and Tert expressing cells resolved into two discreet populations, which were stable over time. Intestinal organoids derived from cancer-prone Apc(Min/+) mice showed similar numbers of ISCs, but had reduced Math1 expression, indicating a suppressed secretory cell differentiation potential (as found in intestinal tissue). Apc(Min/+) organoids were used to screen epigenetically active compounds for those that increased Math1 expression and organoid differentiation (including HDAC inhibitors, Sirtuin (SIRT) modulators and methyltransferase inhibitors). Broad-spectrum HDAC inhibitors increased both Math1 and Muc2 expression, indicating an ability to promote the suppressed secretory cell differentiation pathway. Other epigenetic compounds had a diverse impact on cell differentiation, with a strong negative correlation between those that activated the secretory marker Muc2 and those that activated the absorptive cell marker Fabp2. These data show that ESC-derived intestinal organoids can be derived in large numbers, contain distinct ISC types and can be used to screen for agents that promote cell differentiation through different lineage pathways.
=>1.時代, 季節, 歳月, 当時, 現代, 一生, 年季, 就業時間, 期間, 時刻, 時点, 機会, 拍子, 速度, 何度, 何回,
時, 時間, 回, 2.時間[速度]を測定する, 時間を決める, (装置などの)タイミングを調節する
Overview of noun time
The noun time has 10 senses (first 9 from tagged texts)
1. (219) time, clip -- (an instance or single occasion for some event; "this time he succeeded"; "he
called four times"; "he could do ten at a clip")
2. (160) time -- (a period of time considered as a resource under your control and sufficient to
accomplish something; "take time to smell the roses"; "I didn't have time to finish"; "it took more
than half my time")
3. (114) time -- (an indefinite period (usually marked by specific attributes or activities); "he
waited a long time"; "the time of year for planting"; "he was a great actor in his time")
4. (43) time -- (a suitable moment; "it is time to go")
5. (36) time -- (the continuum of experience in which events pass from the future through the
present to the past)
6. (10) time -- (a person's experience on a particular occasion; "he had a time holding back the
tears"; "they had a good time together")
7. (7) clock time, time -- (a reading of a point in time as given by a clock; "do you know what time
it is?"; "the time is 10 o'clock")
8. (5) fourth dimension, time -- (the fourth coordinate that is required (along with three spatial
dimensions) to specify a physical event)
9. (1) meter, metre, time -- (rhythm as given by division into parts of equal duration)
10. prison term, sentence, time -- (the period of time a prisoner is imprisoned; "he served a prison
term of 15 months"; "his sentence was 5 to 10 years"; "he is doing time in the county jail")
Overview of verb time
The verb time has 5 senses (first 3 from tagged texts)
1. (4) clock, time -- (measure the time or duration of an event or action or the person who performs
an action in a certain period of time; "he clocked the runners")
2. (3) time -- (assign a time for an activity or event; "The candidate carefully timed his
appearance at the disaster scene")
3. (1) time -- (set the speed, duration, or execution of; "we time the process to manufacture our
cars very precisely")
4. time -- (regulate or set the time of; "time the clock")
5. time -- (adjust so that a force is applied and an action occurs at the desired time; "The good
player times his swing so as to hit the ball squarely")
--- WordNet end ---