The UPD3 cytokine couples environmental challenge and intestinal stem cell division through modulation of JAK/STAT signaling in the stem cell microenvironment.
The UPD3 cytokine couples environmental challenge and intestinal stem cell division through modulation of JAK/STAT signaling in the stem cell microenvironment.
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DOI：
10.1016/j.ydbio.2012.10.023
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发表时间：
2013-01-15
影响因子：
2.7
通讯作者：
Agaisse, Herve
中科院分区：
文献类型：
--
作者：
Zhou, Feng;Rasmussen, Andrew;Lee, Sangil;Agaisse, Herve
关键词：
在果蝇中，肠上皮细胞(ECs)的替代依赖于肠干细胞(ISCs)的分裂及其后代--肠母细胞(EBS)的分化。最近的研究揭示了JAK/STAT信号在调节ISC分裂速率中的作用，以响应环境挑战。在这里，我们展示了Upd3细胞因子在JAK/STAT依赖的肠道感染反应中的关键作用。我们发现，在ECs和EBS中，UPD3的表达被激活，这两种细胞在对挑战的反应中发生了大规模的分化。我们发现，在EBS和内脏肌(VMs)中，Upd3细胞因子是刺激JAK/STAT信号所必需的，它是在基底膜上分泌和聚集的。我们进一步表明，刺激ISC分裂需要在EBS和VM中激活JAK/STAT信号，但在ISCs中显然不需要。我们的结果表明，EBS和VM分别通过依赖于UPD3的EGF配体Spitz和Vin的产生来调节依赖EGFR的ISC分裂的速率。因此，本研究支持这样的观点，即干细胞后代(ECs和EBS)中Upd3细胞因子的产生通过调节干细胞微环境(EBS和Vms)中的JAK/STAT信号来刺激肠道干细胞分裂。
In Drosophila, the replacement of spent enterocytes (ECs) relies on division of intestinal stem cells (ISCs) and differentiation of their progeny, the enteroblasts (EBs). Recent studies have revealed a role for JAK/STAT signaling in the modulation of the rate of ISC division in response to environmental challenge. Here, we demonstrate the critical role of the Upd3 cytokine in the JAK/STAT-dependent response to enteric infection. We show that upd3 expression is activated in ECs and in EBs that massively differentiate in response to challenge. We show that the Upd3 cytokine, which is secreted basally and accumulates at the basement membrane, is required for stimulation of JAK/STAT signaling in EBs and visceral muscles (VMs). We further show that stimulation of ISC division requires active JAK/STAT signaling in EBs and VMs, but apparently not in ISCs. Our results suggest that EBs and VMs modulate the rate of the EGFR-dependent ISC division through upd3-dependent production of the EGF ligands Spitz and Vein, respectively. This study therefore supports the notion that the production of the Upd3 cytokine in stem cell progeny (ECs and EBs) stimulates intestinal stem cell division through modulation of JAK/STAT signaling in the stem cell microenvironment (EBs and VMs).
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影响因子：
1.2
作者：
Bach, Erika A.;Ekas, Laura A.;Baeg, Gyeong-Hun
通讯作者：
Baeg, Gyeong-Hun
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：
30.3
作者：
Mysorekar IU;Isaacson-Schmid M;Walker JN;Mills JC;Hultgren SJ
通讯作者：
Hultgren SJ
影响因子：
5.5
作者：
Lin, Guonan;Xu, Na;Xi, Rongwen
通讯作者：
Xi, Rongwen
DOI：
10.1073/pnas.070357597
发表时间：
2000-03-28
影响因子：
11.1
作者：
Basset, A;Khush, RS;Lemaitre, B
通讯作者：
Lemaitre, B