New and old techniques in cell and developmental biology.

Differentiation ∎ (∎∎∎∎) ∎∎∎–∎∎∎ Contents lists available at ScienceDirect Differentiation journal homepage: www.elsevier.com/locate/diff Editorial New and old techniques in cell and developmental biology During last year's editorial board meeting, the staff of Differ- entiation agreed that it was timely to organize a Special Issue on Techniques in Cell and Developmental Biology that would en- compass both historic and well as contemporary methods, spelling out in some detail the “tricks” required for success. Accordingly, we have compiled a broad spectrum of papers that cover a dis- parate collection of techniques from classic mesenchymal–epi- thelial interactions (Cunha and Baskin) to generation of genome- edited epiblast stem cells via a detour through embryonic stem cell-chimaeras (Osteil et al.) and to generation and puriﬁcation of stem cell-derived cardiomyocytes (Schwach and Passier). Three related papers deal with an exceptionally useful method for studying in vivo development, cancer modeling and transla- tional cancer research, namely transplantation of organ rudiments (animal or human) or human primary cancers under the renal capsule of immune-deﬁcient mice. The basic methodology of renal capsule grafting (Cunha and Baskin) is described in detail. Through use of immune-compromised mouse hosts it is possible to grow human fetal organs, adult human tissue, primary human tumors and heterospeciﬁc tissues recombinants (e.g., mutant mouse me- senchyme combined with human fetal epithelium) to assess hu- man organogenesis under experimental conditions, to assess di- rect versus indirect effects of mesenchymal gene knockout on human epithelial development and to establish new tumor transplant lines that are particularly informative of tumor cell biology. The widespread use of the mouse as an animal model of human development is predicated on the generally unproven assumption that the molecular mechanisms of human and mouse develop are similar/identical. This is certainly not true in some instances. For example, up-regulation of uterine epithelial progesterone receptor is induced in humans by estrogens (Kurita et al., 2005). In contrast, mouse uterine epithelial progesterone receptor is induced as a result of ovariectomy (the absence of estrogen) (Kurita et al., 2000). While mouse development has progressed to the molecular mechanistic level, our understanding of human development has not reached this level of sophistication, which emphasizes the need for modern detailed analysis of human development. Cunha et al. describe how developing human fetal organs can be isolated from abortus specimens and grown under the renal capsule of host mice where normal development proceeds. Such human fetal organ grafts can then be subjected to a wide array of analytic techniques, and the mouse hosts bearing grafts of human fetal organs can be treated with environmentally relevant agents known or suspected of eliciting adverse developmental effects based upon purely animal studies. Wang et al. describe how the sub-renal capsule graft site can be used to generate patient-derived tumor transplant models that continue to maintain a high degree of biologic ﬁdelity, which in- cludes histopathological and molecular characteristics, tumor heterogeneity, metastatic ability, and response to treatment. In addition, the authors describe the isolation of new transplant lines from heterogeneous primary tumors whose metastatic activity is either minimal or prominently expressed. In so doing the Wang lab has developed new human tumor transplant models for stu- dies of (a) cancer progression, metastasis and drug resistance, (b) evidence-based precision cancer therapy, (c) preclinical drug efﬁcacy testing and (d) discovery of new anti-cancer drug candidates. All organs composed of an epithelial parenchyma develop as a result of interactions between epithelium and mesenchyme in which the mesenchyme induces and speciﬁes epithelial develop- ment. The ﬁrst paper on mesenchymal–epithelial interactions in mammals was published by Clifford Grobstein in the 1950s (Grob- stein, 1953). The basic concepts of mesenchymal–epithelial inter- actions in development have emerged as a result of hundreds of papers, but new opportunities for using this classic technique have emerged with advent of gene knockout mice. Germline knockout mice with phenotype in epithelial development/differentiation beg the question as to whether the epithelial phenotype is due to ab- sence of the gene in the epithelium, mesenchyme or both. Tissue recombinants composed of mutant mesenchyme plus wild-type epithelium or wild-type mesenchyme plus mutant epithelium provide a quick answer to this question without the need of gen- erating conditional gene knockout mice. Cunha and Baskin describe the basic methodology of mesenchymal–epithelial interactions. Another paper related to mesenchymal–epithelial interactions and in vivo development under the renal capsule deals with the isolation and analysis of discreet adult human prostatic epithelial and stromal populations. The paper by Strand et al. provides an excellent conceptual background of prostatic epithelial cells (se- cretory luminal cells, basal cells and neuroendrine cells) and prostatic stromal cells (ﬁbroblasts, smooth muscle cells, vascu- lature cells and myoﬁbroblasts), their origin and biological prop- erties. Methods for isolating and characterizing these cells are described, which can be applied to human prostate as well as other human organs. Isolated human epithelial cells can be used to prepare heterospeciﬁc mouse/human tissue recombinants (Hay- ward et al., 1998) that are useful in analyzing the molecular me- chanisms of human epithelial differentiation, particularly when such heterospeciﬁc mouse/human tissue recombinants are grafted under the renal capsule of immune-deﬁcient mice. http://dx.doi.org/10.1016/j.diff.2016.02.002 Join the International Society for Differentiation (www.isdifferentiation.org) 0301-4681/& 2016 International Society of Differentiation. 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