ERS | monograph Introduction Brigid L.M. Hogan1 and Marko Z. Nikolić 2 @ERSpublications This Monograph considers the different stem cells present in the developing and adult lung, how they can be derived from pluripotent cells, and the cutting-edge research underway to study them and harness their therapeutic potential https://bit.ly/30BDe7h Almost every organ in the adult human body can maintain itself over the long term and undergo repair after injury. These properties are largely dependent on stem cells – cells that can both divide repeatedly to make more of themselves (self-renew) and generate daughters that can give rise to one or more differentiated cell type [1]. This Monograph brings together information about the different classes of stem cells present in both the developing and adult lung: where they are found, how they function in homeostasis and pathologic conditions, the mechanisms that regulate their behaviour, and how they may be harnessed for therapeutic purposes. The focus is on stem cells in the mouse and human lung but includes the ferret as an increasingly important new model organism. Chapters also discuss how lung tissue, including endogenous stem cells, can be generated in vitro from pluripotent stem cell lines. These are undifferentiated stem cells that are normally present transiently in the embryo and have the capacity to generate all the tissues of the body. Pluripotent cells can be generated from adult cells by genetic manipulation but are not present in mature organs themselves. The stem cells of adult organs, including the lung, are laid down during development as integral components of the mature system [2, 3]. Different tissue compartments – the epithelium, stroma and vasculature – contain their own characteristic stem cells, which cannot substitute for one another and are found in characteristic locations. The immediate environment of an adult tissue stem cell is called the niche [4, 5]. In the case of epithelial stem cells, the niche may include the underlying ECM and stromal cells, as well as mechanical and other contact cues from neighbouring epithelial cells. The niche may also include blood vessels and the humoural factors (e.g. hormones, oxygen and nutrients) they deliver, as well as immune cells, lymphatics and nerves. Any attempts to engineer replacement organs like the lung, or to promote the survival and expansion of failing endogenous stem cells with biologics or drugs, must take into account the absolute necessity of also providing robust niches. Without a supportive environment, stem cells may function aberrantly or not at all. In many cases, stem cells can be extracted from an Copyright ©ERS 2021. Print ISBN: 978-1-84984-133-7. Online ISBN: 978-1-84984-134-4. Print ISSN: 2312-508X. Online ISSN: 2312-5098. Correspondence: Brigid L.M. Hogan, Duke University Dept of Cell Biology, Nanaline Duke Building, Room 388, 307 Research Drive, Durham, NC 27710, USA. E-mail: brigid.hogan@duke.edu. Marko Nikolić, UCL Respiratory, Division of Medicine, Rayne Institute, 5 University Street, London, WC1E 6JF, UK. E-mail: m.nikolic@ucl.ac.uk. 1 Dept of Cell Biology, Duke University Medical School, Durham, NC, USA. 2 UCL Respiratory, Division of Medicine, University College London, London, UK. https://doi.org/10.1183/2312508X.10002321 ix