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Nanotechnology in Stem Cell Regenerative Therapy and Its Applications
Published in Harishkumar Madhyastha, Durgesh Nandini Chauhan, Nanopharmaceuticals in Regenerative Medicine, 2022
HSCs can be labelled and tracked with their morphologic nature and cell-surface markers in the bloodstream and target tissues (Lagasse et al. 2000). They exist in the bone marrow and can reform blood-forming lineages. This potential makes it the best-characterised stem cell niche. The missing parts of the haematopoietic system can be replenished by HSCs and can endure freezing for many years.
The Silver Lining
Published in David J. Hackam, Necrotizing Enterocolitis, 2021
Mark R Frey, Misty Good, Steven J. McElroy
The key to understanding the balance of different ISC populations, the cues that drive their division or relative inactivity, and the triggers for differentiation in daughter cells is the concept of the ISC niche. “Stem cell niche” was first coined in the 1970s (43) and is defined as the association of a stem cell with other cells and noncellular elements (e.g., extracellular matrix, extracellular soluble factors) that determine its behavior. Under normal conditions, the LGR5+ ISC proliferates to generate daughter cells that move out of the crypt. These cells become differentiated as they migrate, and both their differentiation and the maintenance of the stem cells in their proper place are driven through gradients and juxtracrine signaling of Bmp, Wnt, Notch, and growth factor pathways (44, 45). In addition to Bmp, Notch signaling helps Lgr5+ cells maintain their stemness (46). Wnt signaling, in partnership with growth factors such as epidermal growth factor (EGF), helps control proliferation (44). Furthermore, while the exact sources of ligands for these pathways are not fully understood, it is important to note that Paneth cells produce EGF, Notch, and Wnt, which in turn promote stem cell proliferation and maintenance (47). In fact, Paneth cells can support Lgr5+ cell growth and survival in vitro and have been proposed as a key nurse cell for the actively dividing stem population (47). Again, Paneth cells and their role in NEC will be covered in depth in Chapter 42.
JAK-STAT pathway: Testicular development, spermatogenesis and fertility
Published in Rajender Singh, Molecular Signaling in Spermatogenesis and Male Infertility, 2019
In the stem cell niche environment, one cell influences the behavior of another through diffusible signaling molecules, which on receptor interaction initiates a cascade of events in the target cell. The JAK-STAT signaling pathway is known to maintain the stem cell population to ensure gamete production throughout the reproductive life. As previously described, the JAK-STAT pathway is well understood in Drosophila because of simple genetics offering a single copy of JAK-STAT components (57) and the availability of easy genetic tools (58). In the stem cell niche microenvironment of Drosophila testis, different cells communicate through ligand-receptor interaction. The hub cells secrete a ligand called Unpaired (Upd) (16), which is recognized by the receptor Domeless of germline stem cells or somatic stem cells lying in close proximity to the hub cells (20,21). This ligand-receptor interaction initiates a downstream signaling cascade, which involves the activation of receptor-associated hopscotch (22), a homolog of JAK and a transcription activator STAT92E localized in the cytoplasm, which enters the nucleus to activate transcription of the target genes (23,24).
Gut bacteria signaling to mitochondria in intestinal inflammation and cancer
Published in Gut Microbes, 2020
Dakota N. Jackson, Arianne L. Theiss
The epithelial lining of the small intestine (SI) is regenerated in its entirety at a rapid pace of every three to five days. In tissues of high turnover such as the intestinal epithelium, stem cells are crucial regulators of tissue homeostasis. Crypt base columnar (CBC) stem cells, a population of rapidly dividing cells at the crypt base expressing leucine-rich-repeat containing G-protein coupled receptor 5 (Lgr5), give rise to all terminally differentiated intestinal epithelial cell (IEC) types (enterocytes, Paneth, goblet, enteroendocrine, tuft, and M cells).33 CBCs divide into progenitor cells which move upward within the crypt into the transit amplifying zone.34 It is here that the cells differentiate further and travel to the villus where their functions are required. At the villus tip, senescent IECs slough off through anoikis, a specific type of programmed cell death for anchorage-dependent cells, and make room for newly formed cells to take their place.34 Paneth cells are the exception as these cells are long-lived secretory cells that migrate to the crypt base and reside between Lgr5+ CBCs where they produce and secrete antimicrobial peptides and stem cell factors such as epidermal growth factor, Wnt3, and Notch ligand D114 that sustain the stem cell niche.35–38 Local conditions in the stem cell niche regulate cell proliferation, differentiation, and stem cell self-renewal.34
Research advances in the regulation of the putative ovarian germline stem cell niche on female germline stem cells
Published in Systems Biology in Reproductive Medicine, 2019
Yangchun Liu, Jiao Xu, Feiyin Zhu, Haifeng Ye, Chuan Hu, Jian Huang, Yuehui Zheng
The environment in which stem cells live consists of niche cells, extracellular matrix, vessels, and cytokines that support stem cell survival. This stem cell microenvironment is also called as stem cell niche (Pan Z et al. 2016). The ovarian germline stem cell niche includes immune cells, cytokines, collagen, enzymes, and their regulation which involves the Hippo and Notch signaling pathways (Sato et al. 2011; Li et al. 2015; Van De Bor et al. 2015; Ye et al. 2016, 2017). Normally, signals under a steady-state as well as cell–cell and cell–matrix interactions are required for the maintenance of the function of stem cells (Ferraro et al. 2010; Rodgers and Rando 2012). The extracellular matrix is a major component of the microenvironment that regulates the polarity of stem cells via the cell–matrix interactions and keeps the balance between self-renewal and differentiation of the stem cells (Ahmed and Ffrench-Constant 2016). The non-stem cells in the ovarian germline stem cell niche, such as cap cells, play an important role in controlling the number, differentiation, and behavior of FGSCs through crosstalk (Song et al. 2007). Additionally, subtle variations in the niche, such as pH, oxygen level, and ion concentration, can also modulate the activity of stem cells (Inaba et al. 2016).
Re-education begins at home: an overview of the discovery of in vivo-active small molecule modulators of endogenous stem cells
Published in Expert Opinion on Drug Discovery, 2018
JungIn Um, Ji-Hyung Lee, Da-Woon Jung, Darren R. Williams
Endogenous stem cells are defined by their ability to carry out two types of division: symmetrically to yield two daughter stem cells or asymmetrically into two distinct cell types: one daughter stem cell phenotypically identical to itself and one ‘progenitor’ cell that is committed to further divide and/or eventually differentiate into the specific tissue type (Figure 1). Endogenous stem cells do not ‘operate’ alone. Within their tissue, stem cells are embedded alongside non-stem cells in an environment termed the stem cell ‘niche.’ This niche also comprises non-cellular components, such as extracellular matrix, matrix-bound growth factors/cytokines and even mechanical factors (such as shear stress) [16], which together provide a complex network of signals regulating stem cell status (an example is shown in Figure 2). Thus, candidate small molecules inducing regenerative responses in stem cells may also work indirectly by affecting components of the stem cell niche. It should also be noted that the hierarchy and potency of stem cells also varies between different tissues. In the bone marrow, HSCs are pluripotent and can differentiate into the various blood cell types. In contrast, skeletal muscle stem cells (termed satellite cells) are unipotent and can only differentiate into skeletal muscle precursors. Additionally, the cell cycle status of endogenous stem cell also varies between tissues. As examples, epithelial stem cells in the small intestine are continuously dividing whereas cardiac stem cells generally reside in a quiescent state and proliferate in response to signals indicating tissue damage.