Enteroid Monolayers Reveal an Autonomous WNT and BMP Circuit Controlling Intestinal Epithelial Growth and Organization.
Enteroid Monolayers Reveal an Autonomous WNT and BMP Circuit Controlling Intestinal Epithelial Growth and Organization.
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DOI：
10.1016/j.devcel.2018.01.024
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发表时间：
2018-03-12
影响因子：
11.8
通讯作者：
Altschuler SJ
中科院分区：
文献类型：
--
作者：
Thorne CA;Chen IW;Sanman LE;Cobb MH;Wu LF;Altschuler SJ
肠上皮细胞在增殖和分化之间保持着显著的平衡，尽管细胞更新很快。一个核心的挑战是阐明组织更新的强大控制所需的机制。相反的WNT和BMP信号传导是建立上皮稳态必不可少的。然而，它一直难以解开组织中的形态发生信号的多个来源的贡献。在这里，解剖上皮自主形态发生信号电路，我们开发了一个肠样细胞单层培养系统，概括了肠上皮的四个关键特性，即能力：维持增殖和分化区，自我更新，再生，并产生主要的肠细胞类型。我们系统地干扰WNT和BMP信号的内在和外在来源，以揭示控制增殖、组织组织形成和细胞命运的核心形态发生回路。我们的工作表明，即使在没有3D组织结构的情况下，肠上皮也能够通过形态发生介导的反馈来控制其自身的生长和组织。Thorne，Chen等人开发了一种肠样细胞单层培养系统，该系统概括了肠上皮的细胞类型组成、隐窝组织和周转动力学。作者使用肠样细胞单层揭示了调节肠上皮细胞增殖和组织组织结构的上皮-内源性Wnt和BMP形态发生回路。
The intestinal epithelium maintains a remarkable balance between proliferation and differentiation despite rapid cellular turnover. A central challenge is to elucidate mechanisms required for robust control of tissue renewal. Opposing WNT and BMP signaling is essential in establishing epithelial homeostasis. However, it has been difficult to disentangle contributions from multiple sources of morphogen signals in the tissue. Here, to dissect epithelial-autonomous morphogenic signaling circuits, we developed an enteroid monolayer culture system that recapitulates four key properties of the intestinal epithelium, namely the ability to: maintain proliferative and differentiated zones, self-renew, polarize, and generate major intestinal cell types. We systematically perturb intrinsic and extrinsic sources of WNT and BMP signals to reveal a core morphogenic circuit that controls proliferation, tissue organization, and cell fate. Our work demonstrates the ability of intestinal epithelium, even in the absence of 3D tissue architecture, to control its own growth and organization through morphogen-mediated feedback. Thorne, Chen et al. develop an enteroid monolayer culture system that recapitulates cell-type composition, crypt organization, and turnover kinetics of the intestinal epithelium. The authors use the enteroid monolayer to uncover an epithelium-intrinsic Wnt and BMP morphogenic circuit that regulates proliferation and tissue organization in the intestinal epithelium.
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影响因子：
12.3
作者：
Carpenter AE;Jones TR;Lamprecht MR;Clarke C;Kang IH;Friman O;Guertin DA;Chang JH;Lindquist RA;Moffat J;Golland P;Sabatini DM
通讯作者：
Sabatini DM
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
29.4
作者：
Farin, Henner F.;Van Es, Johan H.;Clevers, Hans
通讯作者：
Clevers, Hans
影响因子：
64.5
作者：
Gao D;Vela I;Sboner A;Iaquinta PJ;Karthaus WR;Gopalan A;Dowling C;Wanjala JN;Undvall EA;Arora VK;Wongvipat J;Kossai M;Ramazanoglu S;Barboza LP;Di W;Cao Z;Zhang QF;Sirota I;Ran L;MacDonald TY;Beltran H;Mosquera JM;Touijer KA;Scardino PT;Laudone VP;Curtis KR;Rathkopf DE;Morris MJ;Danila DC;Slovin SF;Solomon SB;Eastham JA;Chi P;Carver B;Rubin MA;Scher HI;Clevers H;Sawyers CL;Chen Y
通讯作者：
Chen Y
影响因子：
5.9
作者：
Roman, Adrianna K. San;Jayewickreme, Chenura D.;Murtaugh, L. Charles;Shivdasani, Ramesh A.
通讯作者：
Shivdasani, Ramesh A.