@article {447,
	title = {Next-Generation Surrogate Wnts Support Organoid Growth and Deconvolute Frizzled Pleiotropy In~Vivo.},
	journal = {Cell stem cell},
	volume = {27},
	year = {2020},
	month = {2020 Nov 5},
	pages = {840-851.e6},
	abstract = {Modulation of Wnt signaling has untapped potential in regenerative medicine due to its essential functions in stem cell homeostasis. However, Wnt lipidation and Wnt-Frizzled (Fzd) cross-reactivity have hindered translational Wnt applications. Here, we designed and engineered water-soluble, Fzd subtype-specific "next-generation surrogate" (NGS) Wnts that hetero-dimerize Fzd and Lrp6. NGS Wnt supports long-term expansion of multiple different types of organoids, including kidney, colon, hepatocyte, ovarian, and breast. NGS Wnts are superior to Wnt3a conditioned media in organoid expansion and single-cell organoid outgrowth. Administration of Fzd subtype-specific NGS Wnt in~vivo reveals that adult intestinal crypt proliferation can be promoted by agonism of Fzd5 and/or Fzd8 receptors, while a broad spectrum of Fzd receptors can induce liver zonation. Thus, NGS Wnts offer a unified organoid expansion protocol and a laboratory "tool kit" for dissecting the functions of Fzd subtypes in stem cell biology.},
	issn = {1934-5909},
	doi = {10.1016/j.stem.2020.07.020},
	url = {https://linkinghub.elsevier.com/retrieve/pii/S1934-5909(20)30358-1},
	author = {Miao, Y and Ha, A and de Lau, W and Yuki, K and Santos, AJM and You, C and Geurts, MH and Puschhof, J and Pleguezuelos-Manzano, C and Peng, WC and Senlice, R and Piani, C and Buikema, JW and Gbenedio, OM and Vallon, M and Yuan, J and de Haan, S and Hemrika, W and R{\"o}sch, K and Dang, LT and Baker, D and Ott, M and Depeille, P and Wu, SM and Drost, J and Nusse, R and Roose, JP and Piehler, J and Boj, SF and Janda, CY and Clevers, H and Kuo, CJ and Garcia, KC}
}
