This technique has been combined with microfluidics approaches to assemble spheroids containing two cell types (O’Brien et al
June 12, 2021
This technique has been combined with microfluidics approaches to assemble spheroids containing two cell types (O’Brien et al., 2015). adult-derived organoid YM-58483 systems. We also describe new approaches to reconstitute organoids from purified cellular components, and discuss how this technology can help to address fundamental questions YM-58483 about the adult stem cell niche. models of these processes, as advances in three-dimensional (3D) culture techniques have enabled the expansion of single stem cells into self-organizing tissues that functionally recapitulate key aspects of their tissue of origin. These aspects include the presence of multiple differentiated cell types, self-organization into a stereotyped tissue architecture, and activation of developmental gene expression programs (Camp et al., 2015; Clevers, 2016; Lancaster and Knoblich, 2014). The term organoid can refer to outgrowths from primary tissue explants (as in the mammary field) or to clonal outgrowths from single cells (Simian and Bissell, 2017). In this Review, we focus in particular Rabbit Polyclonal to EPHA3 on stem cell-derived organoids (Fig.?1A) as a model system to interrogate the stem cell niche. These organoids can be derived from embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), or tissue-resident adult stem YM-58483 cells. Organoids grown from pluripotent ESCs or iPSCs mimic embryonic developmental processes, whereas those derived from adult stem cells can be used to model tissue homeostasis and its disruption during disease progression. Together, such organoids, whether derived from pluripotent or adult stem cells, represent a diversity of organotypic cultured tissues that each recapitulate aspects of brain, retina, stomach, prostate, liver or kidney structure (Clevers, 2016; Lancaster YM-58483 and Knoblich, 2014). Open in a separate window Fig. 1. Advantages of organoid models for studying adult stem cells. YM-58483 (A) Organoids grown clonally from single cells can be used to prospectively identify adult stem cell populations based on the capacity of a cell to form organoids. (B) Organoids can be derived from human cells as well as non-human cells such as mouse or zebrafish, which allows modeling of human-specific stem cell biology and the identification of differences between human and non-human tissues. (C) culture allows in-depth experimental perturbation and imaging of stem cells in their surrounding niche. Different approaches include tightly controlled chemical or genetic manipulation, 3D imaging of live tissues over time (4D imaging), high-throughput combinatorial screening, and single-cell resolution imaging to analyze specific cell-cell interactions. As well as providing an easily accessible platform for understanding development and disease, organoids, especially those derived from adult stem cells, provide a convenient means to investigate stem cell-niche interactions (Box?1). The stem cell niche can be defined as the local environment that surrounds a stem cell, which directly influences stem cell behavior and fate (Scadden, 2014). Indeed, some evidence suggests that in many cases the stem cell niche C rather than the stem cell itself C is the functional unit that controls cell fate. For example, transplantation into the mammary gland microenvironment reprograms single neural stem cells into mammary epithelial cells that can regenerate the mammary epithelial tree (Booth et al., 2008). The individual components that comprise the stem cell niche depend on the specific tissue, but include factors such as other differentiated cell types, signaling molecules, extracellular matrix (ECM) components, the 3D shape and arrangement of cells, and mechanical forces such as tension, rigidity and even fluid flow. Although many important niche components have been identified for different adult stem cell populations throughout the body, there are still many unknowns. In particular, it has been difficult to dissect the precise mechanism by which individual components regulate the niche owing to their interdependence. While animal studies have proven invaluable in defining the concept of the stem cell niche and identifying key stem cell-niche interactions, organoids serve as a complementary approach.