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| ==HSC== | |||
| Haematopoietic and mesenchymal stem cells are known to regulate the immune response. | Haematopoietic and mesenchymal stem cells are known to regulate the immune response. | ||
| Canonical Wnt signalling is thought not to be involved in HSC regulation as KO of α- β- and γ-catenin produced no apparent phenotype. However, different experiments show different effects of Wnt signalling. Some shows that APC, part of the destruction complex destroying intracellular β-catenin levels, is required for HSC survival; while GSK3β, also part of the destruction complex, when inhibited promotes progenitors to expand while retaining HSCs. Dkk1 (binds to LRP6 and inhibit Wnt) expression impairs HSC function. These contrasting results probably means that different Wnt levels leads to different outcomes, and Wnt signalling in the HSC niche needs to be within optimal level. | |||
| Other factors that contribute the niche, and the associated receptor on the HSC includes VCAM1/α4β1 integrin, SCF/KIT, THPO/MPL, ANGPT1/TIE2, HoxB4 | |||
| ''In vitro'', osteoblasts produce haematopoietic growth factors that support HSC. | |||
| Calcium ion contribute to the niche and binds to CASR on the HSC for signalling, and is generated from osteoclasts eating the bone. | |||
| Parathyroid hormone (PTH) is a regulator which encourages bone resorption to harvest the calcium stored in bones; however, when given as a periodic dose, actually increases bone mass by increasing the number of osteoblasts<ref>{{cite journal|doi=10.1073/pnas.1120735109}}</ref>. PTH binds to PTH/parathyroid hormone-related protein receptor (PPR or PTHR1) on bone cells<ref>{{cite journal|doi=10.1073/pnas.1120735109}}</ref>and expands the osteoblast compartment and HSC pool via activation of the Wnt<ref>{{cite journal|doi=10.1073/pnas.1120735109}}</ref> and Notch signalling. However, immunofluorescence of bone sections shows the HSC are located near blood vessels and not next to osteoblasts, thus, there is a debate as to whether osteoblasts are the niche cells which interact with HSC. | |||
| HSC homing is mediated by the nervous system. UDP-galactose ceramide galactosyltransferase-deficient (''Cgt<sup>-''/''-''</sup>) mice is a line which exhibit aberrant nerve conduction, dysregulated adrenergic tone (lack of stimulation from adrenaline via the sympathetic nervous system), dysregulated osteoblast function as well as dysregulated bone CXCL12; in these mice, virtually none of the HSPCs observed to migrate out from the bone marrow, even after stimulation with granulocyte colony-stimulating factor (G-CSF) or fucoidan. | |||
| The mechanism is as follows: the sympathetic nervous system stimulation leads to a release of norepinephrine (NE), which suppresses G-CSF-induced osteoblast and they become flatter and have a shorter protrusion. CXCL12 is downregulated and this means the HSPC mobilize and exit the bone marrow. Ablation of NE signals using drugs or genetic engineering leads to lack of mobilization, adminstration of a β<sub>2</sub>adrenergic agonist further increase mobility in both wildtype and NE-deficient mice.<ref>{{cite journal|pmid=16439213|year=2006|last1=Katayama|first1=Y|last2=Battista|first2=M|last3=Kao|first3=WM|last4=Hidalgo|first4=A|last5=Peired|first5=AJ|last6=Thomas|first6=SA|last7=Frenette|first7=PS|title=Signals from the sympathetic nervous system regulate hematopoietic stem cell egress from bone marrow|volume=124|issue=2|pages=407–21|doi=10.1016/j.cell.2005.10.041|journal=Cell}}</ref> | |||
| adipocytes (inhibits HSC, and transplantation into marrow with no fat allows faster engraftment) | |||
| HSC proliferate after injury by BrdU treatment, IFNγ treatment, LPS treatment and 5-fluoro-uracil treatment, but goes back into quiescence after. | |||
| MSC are purified from the bone marrow using the fact that MSCs are adherent to plastic culture dishes, whereas HSCs are not. Macrophages are also adherent and so must be separated from MSCs. | |||
| ==Neural stem cells== | |||
| Neural stem cells differentiate into early neuroepithelial stem cells which transitions into radial glia which forms astrocytes. Some astrocytes remain as stem cells and produces new neurons that get integrated into the network; this differentiation occurs in a defined temporal sequence.<ref>{{cite journal|doi=10.1038/35102174|year=2001|last1=Temple|first1=Sally|journal=Nature|volume=414|issue=6859|pages=112–7|pmid=11689956|title=The development of neural stem cells}}</ref> | |||
| ===Lung stem cells=== | |||
| The exchange of gases from the air in the lungs and the blood is mediated through structures called alveoli. There are three types of cells in the alveoli - alveolar cell type I, II and alveolar macrophages. Alveolar cell type II makes up 3% of the alveolar surface, they are usually found in clusters and secretes surfactants, with the major component being dipalmitoylphosphatidylcholine (DPPC). Surfactants are agents which lowers the surface tension between different phases, such as that between gases and liquids, allowing the alveolar wall to be more permeable to gas exchanges. Alveolar cell type I makes up the rest of the alveolar surface, and contributes to turning over surfactants via pinocytotic vesicles. Alveolar macrophages are not part of the alveolar wall but found on the wall and helps fight off pathogens. Activity of the alveolar macrophage is relatively high, because they are located at one of the major boundaries between the body and the outside world. | |||
| The bronchioles are tubular structures next to the alveoli that connects the alveoli with the bronchi, it is the last branching structure before the alveoli and dissipates the air pressure to prevent physical damage. There are different types of cells in the bronchioles - cuboidal epithelial cells, ciliated cells, clara cells (which secretes glycosaminoglycans surfactants to protect the bronchiole lining) and neuroendocrine cells (which senses hypoxia through O<sub>2</sub>-activated K<sup>+</sup> channels and regulates growth and regeneration) | |||
| ===Liver stem cell=== | |||
| The liver is made up of many lobes and is composed of hepatocytes, bile duct epithelium, Stellate cells, Kupffer cells, vascular epithelium, fibroblasts and leukocytes. | |||
| ===Pancreatic stem cell=== | |||
| The pancreas can be viewed as two organs into one. Exocrine pancreas produces digestive enzymes to release into the intestine, while the endocrine pancreas contains islet cells that produce insulin, glucagon and somatostatin, required for maintaining glucose level. In type I diabetes, autoimmune responses eliminates beta cells, and so no insulin is produced, meaning the body no longer stores glucose and so leads to high blood sugar levels. | |||
Revision as of 21:37, 4 January 2013
Intestinal crypt
Intestinal sub-epithelial myofibroblasts are SMA, desmin cells that secretes HGF, KGF, TGFβ and regulates epithelial cell's differentiation. Interstitial cells of Cajal are SMA, desmin, c-Kit and CD45 cells in proximity of neurons, to transmit electrical potential that regulates movement of the gastrointestinal tract.
Previously, mesenchymal cells (which are normally the niche cells) are thought to be required to maintain primary intestinal epithelial culture. However, in these cell cultures, Lgr5 ISCs are not observed.
Note that Lgr are also found in multipotent stem cells of the pylorus, and that Lgr cells and Sox2 cells do not overlap, at least not at the levels observable by immunohistochemistry. Using Ki67 as a proliferation marker, it was shown that about half of the Sox2 cells proliferate in homeostatic conditions,showing heterogeneity within the adult stem cell population.
Hair follicle
The cells near the dermis expresses markers such as keratin 5/14. Different markers are also expressed - keratin 1/10, involucrin, cornifin, and transglutaminase-1 are xpressed in the spinous layer of the epidermis; loricrin, filaggrin, and keratohyalin are expressed in granular layers of the epidermis.
The heterogeneity can be attributed to the location in the body. Follicle morphogenesis comes in waves, guard follicles are generated around E14.5 and have long straight shafts, awl and auchene follicles are generated around E16.5 and have long, straight or singly-kinked shafts, shafts on the back of mice are generated around E18.5 and is shaped like a zigzag (with two kinks).
Only a low level of β-catenin is required for hair follicle fomation from sebaceous glands and interfollicular epidermis, whereas a high level of β-catenin is required for new follicles to form from preexisting follicles; this can be a mechanism in which hair follicle formation is controlled which has a large leeway.
The mouse dermis taken from sites of hair formation can induce follicles in any epithelium when transplanted, whereas dermis taken from sites of non-hair formation cannot induce follicles.
fibroblasts from the head and face derive from the neural crest, dorsal and ventral trunk fibroblasts are derived from the dermomyotome of somitic and lateral plate, respectively.
Mice are born nude, and hair begin to grow only after about 10 days. The first two cycles are synchronized, after which they become desynchronized. Thus, it is advisable to study young mice, as they are all synchronized and expresses the same factors.
HSC
Haematopoietic and mesenchymal stem cells are known to regulate the immune response.
Canonical Wnt signalling is thought not to be involved in HSC regulation as KO of α- β- and γ-catenin produced no apparent phenotype. However, different experiments show different effects of Wnt signalling. Some shows that APC, part of the destruction complex destroying intracellular β-catenin levels, is required for HSC survival; while GSK3β, also part of the destruction complex, when inhibited promotes progenitors to expand while retaining HSCs. Dkk1 (binds to LRP6 and inhibit Wnt) expression impairs HSC function. These contrasting results probably means that different Wnt levels leads to different outcomes, and Wnt signalling in the HSC niche needs to be within optimal level.
Other factors that contribute the niche, and the associated receptor on the HSC includes VCAM1/α4β1 integrin, SCF/KIT, THPO/MPL, ANGPT1/TIE2, HoxB4
In vitro, osteoblasts produce haematopoietic growth factors that support HSC.
Calcium ion contribute to the niche and binds to CASR on the HSC for signalling, and is generated from osteoclasts eating the bone.
Parathyroid hormone (PTH) is a regulator which encourages bone resorption to harvest the calcium stored in bones; however, when given as a periodic dose, actually increases bone mass by increasing the number of osteoblasts. PTH binds to PTH/parathyroid hormone-related protein receptor (PPR or PTHR1) on bone cellsand expands the osteoblast compartment and HSC pool via activation of the Wnt and Notch signalling. However, immunofluorescence of bone sections shows the HSC are located near blood vessels and not next to osteoblasts, thus, there is a debate as to whether osteoblasts are the niche cells which interact with HSC.
HSC homing is mediated by the nervous system. UDP-galactose ceramide galactosyltransferase-deficient (Cgt/-) mice is a line which exhibit aberrant nerve conduction, dysregulated adrenergic tone (lack of stimulation from adrenaline via the sympathetic nervous system), dysregulated osteoblast function as well as dysregulated bone CXCL12; in these mice, virtually none of the HSPCs observed to migrate out from the bone marrow, even after stimulation with granulocyte colony-stimulating factor (G-CSF) or fucoidan.
The mechanism is as follows: the sympathetic nervous system stimulation leads to a release of norepinephrine (NE), which suppresses G-CSF-induced osteoblast and they become flatter and have a shorter protrusion. CXCL12 is downregulated and this means the HSPC mobilize and exit the bone marrow. Ablation of NE signals using drugs or genetic engineering leads to lack of mobilization, adminstration of a β2adrenergic agonist further increase mobility in both wildtype and NE-deficient mice.
adipocytes (inhibits HSC, and transplantation into marrow with no fat allows faster engraftment)
HSC proliferate after injury by BrdU treatment, IFNγ treatment, LPS treatment and 5-fluoro-uracil treatment, but goes back into quiescence after.
MSC are purified from the bone marrow using the fact that MSCs are adherent to plastic culture dishes, whereas HSCs are not. Macrophages are also adherent and so must be separated from MSCs.
Neural stem cells
Neural stem cells differentiate into early neuroepithelial stem cells which transitions into radial glia which forms astrocytes. Some astrocytes remain as stem cells and produces new neurons that get integrated into the network; this differentiation occurs in a defined temporal sequence.
Lung stem cells
The exchange of gases from the air in the lungs and the blood is mediated through structures called alveoli. There are three types of cells in the alveoli - alveolar cell type I, II and alveolar macrophages. Alveolar cell type II makes up 3% of the alveolar surface, they are usually found in clusters and secretes surfactants, with the major component being dipalmitoylphosphatidylcholine (DPPC). Surfactants are agents which lowers the surface tension between different phases, such as that between gases and liquids, allowing the alveolar wall to be more permeable to gas exchanges. Alveolar cell type I makes up the rest of the alveolar surface, and contributes to turning over surfactants via pinocytotic vesicles. Alveolar macrophages are not part of the alveolar wall but found on the wall and helps fight off pathogens. Activity of the alveolar macrophage is relatively high, because they are located at one of the major boundaries between the body and the outside world.
The bronchioles are tubular structures next to the alveoli that connects the alveoli with the bronchi, it is the last branching structure before the alveoli and dissipates the air pressure to prevent physical damage. There are different types of cells in the bronchioles - cuboidal epithelial cells, ciliated cells, clara cells (which secretes glycosaminoglycans surfactants to protect the bronchiole lining) and neuroendocrine cells (which senses hypoxia through O2-activated K channels and regulates growth and regeneration)
Liver stem cell
The liver is made up of many lobes and is composed of hepatocytes, bile duct epithelium, Stellate cells, Kupffer cells, vascular epithelium, fibroblasts and leukocytes.
Pancreatic stem cell
The pancreas can be viewed as two organs into one. Exocrine pancreas produces digestive enzymes to release into the intestine, while the endocrine pancreas contains islet cells that produce insulin, glucagon and somatostatin, required for maintaining glucose level. In type I diabetes, autoimmune responses eliminates beta cells, and so no insulin is produced, meaning the body no longer stores glucose and so leads to high blood sugar levels.
- Evans, GS; Flint, N; Somers, AS; Eyden, B; Potten, CS (1992). "The development of a method for the preparation of rat intestinal epithelial cell primary cultures". Journal of cell science. 101 ( Pt 1): 219–31. PMID 1569126.
- Barker, N; Huch, M; Kujala, P; Van De Wetering, M; Snippert, HJ; Van Es, JH; Sato, T; Stange, DE; Begthel, H (2010). "Lgr5(+ve) stem cells drive self-renewal in the stomach and build long-lived gastric units in vitro". Cell stem cell. 6 (1): 25–36. doi:10.1016/j.stem.2009.11.013. PMID 20085740.
- Cite error: The named reference
Doistemwas invoked but never defined (see the help page). - Silva-Vargas, Violeta; Lo Celso, Cristina; Giangreco, Adam; Ofstad, Tyler; Prowse, David M.; Braun, Kristin M.; Watt, Fiona M. (2005). "Β-Catenin and Hedgehog Signal Strength Can Specify Number and Location of Hair Follicles in Adult Epidermis without Recruitment of Bulge Stem Cells". Developmental Cell. 9 (1): 121–31. doi:10.1016/j.devcel.2005.04.013. PMID 15992546.
- . doi:10.1073/pnas.1120735109.
{{cite journal}}: Cite journal requires|journal=(help); Missing or empty|title=(help) - . doi:10.1073/pnas.1120735109.
{{cite journal}}: Cite journal requires|journal=(help); Missing or empty|title=(help) - . doi:10.1073/pnas.1120735109.
{{cite journal}}: Cite journal requires|journal=(help); Missing or empty|title=(help) - Katayama, Y; Battista, M; Kao, WM; Hidalgo, A; Peired, AJ; Thomas, SA; Frenette, PS (2006). "Signals from the sympathetic nervous system regulate hematopoietic stem cell egress from bone marrow". Cell. 124 (2): 407–21. doi:10.1016/j.cell.2005.10.041. PMID 16439213.
- Temple, Sally (2001). "The development of neural stem cells". Nature. 414 (6859): 112–7. doi:10.1038/35102174. PMID 11689956.