Escargot maintains stemness and suppresses differentiation in Drosophila intestinal stem cells.
Escargot maintains stemness and suppresses differentiation in Drosophila intestinal stem cells.
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DOI：
10.15252/embj.201489072
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发表时间：
2014-12-17
期刊：
影响因子：
--
通讯作者：
Edgar BA
中科院分区：
文献类型：
--
作者：
Korzelius J;Naumann SK;Loza-Coll MA;Chan JS;Dutta D;Oberheim J;Gläßer C;Southall TD;Brand AH;Jones DL;Edgar BA
Snail家族转录因子在多种干细胞类型中表达，但它们在维持干细胞身份方面的功能尚不清楚。在成年果蝇中肠中，Snail同源物Esg在肠干细胞（ISCs）及其短暂未分化的子代（称为肠母细胞（EB））中表达。我们在这里证明，在这些祖细胞的esg的损失导致他们迅速分化为肠上皮细胞（EC）或肠内分泌细胞（EE）。相反，肠祖细胞中Esg的强制表达阻断了分化，将ISC锁定在干细胞状态。细胞类型特异性转录组分析结合Dam-ID结合研究确定Esg为干细胞和祖细胞中分化基因的主要阻遏物。发现Esg的一个关键靶点是POU结构域转录因子Pdm 1，其通常在分化的EC中特异性表达。Pdm 1在祖细胞中的异位表达足以驱动其分化为EC。因此，Esg是一个关键的干细胞决定因素，通过抑制分化促进因子（如Pdm 1）来维持干细胞性。
Snail family transcription factors are expressed in various stem cell types, but their function in maintaining stem cell identity is unclear. In the adult Drosophila midgut, the Snail homolog Esg is expressed in intestinal stem cells (ISCs) and their transient undifferentiated daughters, termed enteroblasts (EB). We demonstrate here that loss of esg in these progenitor cells causes their rapid differentiation into enterocytes (EC) or entero-endocrine cells (EE). Conversely, forced expression of Esg in intestinal progenitor cells blocks differentiation, locking ISCs in a stem cell state. Cell type-specific transcriptome analysis combined with Dam-ID binding studies identified Esg as a major repressor of differentiation genes in stem and progenitor cells. One critical target of Esg was found to be the POU-domain transcription factor, Pdm1, which is normally expressed specifically in differentiated ECs. Ectopic expression of Pdm1 in progenitor cells was sufficient to drive their differentiation into ECs. Hence, Esg is a critical stem cell determinant that maintains stemness by repressing differentiation-promoting factors, such as Pdm1.
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影响因子：
11.8
作者：
Lai, Sen-Lin;Miller, Michael R.;Robinson, Kristin J.;Doe, Chris Q.
通讯作者：
Doe, Chris Q.
影响因子：
21.3
作者：
Batlle, E;Sancho, E;de Herreros, AG
通讯作者：
de Herreros, AG
影响因子：
5.5
作者：
Lin, Guonan;Xu, Na;Xi, Rongwen
通讯作者：
Xi, Rongwen
影响因子：
23.9
作者：
Jiang H;Grenley MO;Bravo MJ;Blumhagen RZ;Edgar BA
通讯作者：
Edgar BA
影响因子：
9.2
作者：
Furriols, M;Bray, S
通讯作者：
Bray, S