Essay topic 1: stem cell niche Flashcards
(9 cards)
what is the stem cell niche?
The stem cell niche represents a defined anatomical compartment that provides signals to stem cells in the form of secreted and cell surface molecules to control the rate of stem cell proliferation, determine the fate of stem cell daughters and protect stem cells from exhaustion or death. The niche consists of the stem cells themselves as well as their progeny but also multiple heterologous cell types and a niche-specific ECM. Components can also include neural inputs, soluble factors, vascular network and cell adhesion components. the niche thus provides soluble, adhesive and physical signals to stem cells which are crucial for maintaining stem cell functions. Once formed these niches respond dynamically to homeostatic and regenerative cues and can exhibit substantial physiological alterations that affect how they interact with the stem cells they support.
history of the stem cell niche?
The stem cell niche hypothesis was proposed by schofield in 1978. proposed that stem cells reside in niches (specialised microenvironment) which are conductive to the maintenance of definitive stem cell properties. Hypothesised that the ability of stem cells to self-renew and retain their identity depends on the environment provided by neighbouring (non-hsc) cells and that the progeny of stem cell will undergo differentiation unless they can occupy a similar niche. Experiments in model organisms like worms or flies provided the first in vivo visualisation of the niche and genetic experiments confirmed its importance in regulating stem cell behaviour. Tools for labelling stem cells facillitated localisation and characterisation of stem cell niches in mammalian tissue. These studies show the niches are very varied. Some show the existence of distinct functional c;asses of niche specialised to sustain unique functions of particular niches .
Importance of proper niche functioning?
Increasing evidence implicates deregulation of the stem cell niche as a proximal cause of many pathologies associated with tissue degeneration, ageing and tumorigenesis.
what exactly does the niche do?
signals that emanate from the niche regulate stem cell self-renewal, survival and maintenance. the particular spatial relationship between stem cells and support cells can polarise stem cells within the niche to promote asymmetric stem cell divisions. adhesion between stem cells and supporting stromal cells and/or extracellular matrix anchors stem cells within the niche in close proximity to self renewal and survival signals. So stem cell niche provides structual support, trophic support, topographical information and physiological cues to reg stem cell functions.
where do haematopoietic stem cells reisde?
HSCs reside along the endosteal surface of the trabecular bone in close proximity to both bone-forming osteoblasts and the endothelial cells that line blood vessels. HSCs can leave this niche and their proximity to endothelial cells may facillitate mobalisation from the bone marrow into the circulation.
Neural stem cells?
NSCs can be found within the subventricular zone of the hippocampus and the olfactory bulb and within both niches they are located adjacent to endothelial cells. their close association with the tissue vasculature could be important to expose them to systemic factors that may promote survival, regulate self-renewal and differentiation potential and/or communicate ‘damage’ signals to activate their proliferation,
Intestinal stem cell niche?
ISCs are maintained as ISCs by the physical niche they reside within that comprises of direct ligand-mediated contact with other cell populations and the extracellular matrix, chemokine, cytokine and growth factor signalling. Once the niche becomes unfavourable for stem cell activity, ISC phenotype can change and stemness is los (Duckworth 2021) Within the mammalian small intestine, intestinal stem cells (ISCs) reside at the base of intestinal crypts, where they divide to produce progeny that migrate upwards towards villi that extend into the intestinal lumen. A population of quiescent, reserve stem cells that have capacity to re-populate intestinal epithelia upon intestinal injury are also found around four cell positions from the crypt base. (Duckworth 2021) The actively cycling ISCs, marked by Lgr5 expression, are known as crypt base columnar (CBC) cells and are interspersed between Paneth cells, which provide essential niche signals such as Wnt, Notch, and EGF to maintain ISC function. Niche signals controlling lineage hirearchies and dynamics during homeostasis. Stromal cells and paneth cells provide ISCs with essential niche signals such as wnts to support intestinal homeostasis. Paneth cells play a role in immunity and host-defense but also secrete important signaling molecules such as WNT3, EGF, Notch ligand DLL4. Co-culturing LGR5+ ISCs with a paneth cell-enriched population or adding exogenous WNT3A enhances their efficiency in forming differnentiated intestinal organoids in vitro.
Wnt signaling promotes ISC proliferation, expansion of transit-amplifying (TA) cells, and Paneth cell differentiation
In the intestine progenitors and also enterocytes can differentiate to LGR5+ ISCs through WNT-mediated niche signals. Notch signaling is crucial for asymmetric division, suppressing differentiation into secretory lineages (e.g., goblet and enteroendocrine cells) and promoting enterocyte fate
1.2.1. ECs as stem cell niches
Controlling stem cell division is essential for tissue regeneration when enterocytes die after injury. Following infection, studies have identified an amplification feedback loop between ECs and ISCs for intestinal regeneration (Jiang et al., 2009; Buchon et al., 2009). While ECs generate reactive oxygen species (ROS) for bacterial clearance, ROS also damage ECs. ECs upon damage secrete the cytokines Upd2 and Upd3, which activate JAK/STAT signaling in stem cells in cooperation with other pathways to induce stem cell division to regenerate the intestine (Jiang et al., 2011; Buchon et al., 2009). Several other signaling mediators and pathways have also been identified in ECs that contribute to stem cell division and differentiation (Zhou et al., 2017; Nassari et al., 2022; Wei et al., 2020).
EBs differentiate into other intestinal cell types, including ECs and enteroendocrine cells. Recent studies found that caspase-mediated apoptosis occurs in EBs and the study proposed an adaptive mechanism whereby intestinal stem cells eliminate excess EBs to tightly control differentiation processes. In addition, EBs form extended cell-cell contacts with stem cells and ECs to control the rate of stem cell differentiation.
Zhou and Boutros (2023)
Immune cells within stem cell niches?
Immunological cells provide dynamic regulation of the niche during inflammation and tissue damage. Immune cells like regulatory T cells have an important immunosuppressive function. In the hematopoeitic stem cell niche they generate an immunprivleged microenvironment that promotes stem cell persistence.
spatial cues?
topological organisation of stem cells with respect to the surrounding support cells can have an important role in maintaining appropriate stem cell numbers, polarised attachment to support cells or to the ecm through junctional complexes or asymetrically localised factors within the niche can provide cues that orientate stem cell division and/or specificy different cell fates for stem cell progeny,
