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Adult stem cells (also known as somatic stem cells or tissue stem cells) are rare populations of cells that are found in the body throughout the majority of postnatal life and give rise to a limited number of mature cell types that build the tissue in which they reside. Their progeny replaces cells that are lost owing to tissue turnover or injury, thus ensuring the maintenance of tissue homeostasis. Well-studied examples in mammals include blood, skin, intestine and muscle stem cells, but it is not clear whether all organs contain dedicated tissue-specific stem cells. This serieslooks at the progress that has been made in identifying stem cells in different tissues and in understanding their regulation during normal tissue turnover and following injury.
Pools of quiescent adult stem cells support tissue turnover and regeneration in mammals. Recent studies shed new light on the roles of post-transcriptional mechanisms in controlling entry into, maintenance of and exit from the quiescent state, with important implications for regenerative medicine.
Stem cell function declines during ageing, resulting in the loss of tissue integrity and health deterioration. Ageing is associated with defects in the maintenance of stem cell quiescence and cell differentiation ability, clonal expansion and infiltration of immune cells in the niche. This Review discusses the mechanisms underlying ageing in stem cells and their niches, and potential rejuvenation strategies.
The metabolism of somatic stem cells must be regulated to meet their specific needs, to enable long-term maintenance as well as their activation, proliferation and subsequent differentiation. Better understanding of metabolic regulation in stem cells will open new opportunities to manipulate stem cell function, with potential applications in tissue regeneration and cancer prevention.
Liver regeneration involves multiple cell types, including hepatocytes, hepatic stellate cells, endothelial cells and inflammatory cells. Recent studies have elucidated the interactions between these cells during regeneration as well as the mechanisms that regulate cell proliferation and fibrosis remodelling, and have uncovered macrophages as key players. Such findings can help design novel therapeutic approaches.
Stromal progenitor cells contribute to the maintenance of tissue homeostasis in different organs. In vitro, these mesenchymal stromal cells (MSCs) can differentiate into many cell types. Recent omics and single-cell studies provide insights into the gene regulatory networks that drive lineage determination and cell differentiation, which has implications for the understanding of human diseases and for the development of cell-based therapies.
Direct reprogramming converts cells from one lineage into cells of another without going through an intermediary pluripotent state. This Review describes our current understanding of the molecular mechanisms underlying direct reprogramming as well as the progress in improving its efficiency and the maturation of reprogrammed cells, and the challenges associated with its translational applications.
The intestinal epithelium undergoes rapid turnover and is constantly exposed to hostile luminal contents. Recent insights from single-cell transcriptomics and organoid models have revealed that tissue repair is dependent on cell lineage plasticity and signals originating from different niche components.
This Review discusses the cell types, critical genes and transcription factors involved in bone development and repair. The dysfunctional cellular and molecular signalling that results in clinical bone disease is also outlined, thus informing the current state of science and clinical practice.
Human organoids are valuable models for the study of development and disease and for drug discovery, thus complementing traditional animal models. The generation of organoids from patient biopsy samples has enabled researchers to study, for example, infectious diseases, genetic disorders and cancers. This Review discusses the advantages, disadvantages and future challenges of the use of organoids as models for human biology.
The haematopoietic stem cell (HSC) niche in the bone marrow ensures haematopoiesis by regulating the function of HSCs and progenitor cells. An improved understanding of this regulation in homeostasis, ageing and cancer should aid the development of therapies to rejuvenate aged HSCs or niches and treat malignancies.
Decline in stem cell function causes loss of tissue homeostasis and increased incidence of age-related diseases. During ageing, adult stem cells accumulate damage and the niche in which they reside malfunctions. These defects are associated with changes in the epigenome that contribute to organ dysfunction and disease.
Human pluripotent stem cells constitute a unique system to study the earliest stages of human embryonic haematopoiesis and the origins of human blood cell diseases, and they are an invaluable tool for the generation of haematopoietic stem and progenitor cell populations for cell-based regenerative therapies.
The role of epigenetic regulation in adult stem cell function depends on the specific tissue and factor, but it commonly affects stem cell maintenance, self-renewal and differentiation without disrupting germ-layer fate.
Some terminally differentiated cells have the capacity to de-differentiate or transdifferentiate under physiological conditions as part of a normal response to injury. Recent insights have been gained into the role of this cell plasticity in maintaining tissue and organ homeostasis, and this has important implications for cell-based therapies.
Adult muscles contain quiescent stem cells, known as satellite cells, which are activated upon injury, enabling muscle repair and replenishment of the stem cell pool. Recent studies have shed light on the molecular circuitry regulating satellite cell fate decision and the impairment of this circuitry during degenerative muscle diseases and ageing.
At each ovulation cycle, the single-layer epithelia that encapsulate mammalian ovaries undergo rupture and rapid repair. Recent studies have identified stem cell pools that ensure ovarian epithelial homeostasis, thus providing insights into the regulation of stem cell function and the contribution of stem cells to ovarian tumorigenesis.
Somatic stem cells are responsible for tissue maintenance and repair throughout life. Studies on blood, skin and intestinal epithelium have revealed that multiple types of stem cells with distinct roles perform such regenerative functions. Moreover, stem cells have greater developmental flexibility than had previously been appreciated under stress conditions such as acute injury.