Chapter 5: Stem Cell Niches II Flashcards
HSCs (hematopoeitic stem cells) are located near ___, __ cells and __ cells
osteocytes, endothelial and stromal cells.
Outline and name the process that allows for the deposition of HSCs into the bone marrow.
in embryo, HSCs are actually found in the liver and in the blood vessels. When bone starts forming vascularization, HSCs get deposited in the middle of the bone in the marrow.
This is known as HOMING. Ability for HSCs to migrate through the circulatory system and find their tissue-specific destination.
What is the mechanism of homing
HSCs have a CXCL4 receptor that senses CXCL12 chemokine expressed by osteoblasts and stromal cells of the marrow. Adhestion proteins like E-selectins and Vcam1 support HSC homing into the bones.
HSCs have a ___ receptor that senses ___ chemokine expressed by osteoblasts and stromal cells of the marrow. Adhestion proteins like E-___ and ___ support HSC homing into the bones.
HSCs have a CXCL4 receptor that senses CXCL12 chemokine expressed by osteoblasts and stromal cells of the marrow. Adhestion proteins like E-selectins and Vcam1 support HSC homing into the bones.
2 niches of HSC
1) endosteal niche
2) perivascular niche
in the endosteal niche, the HSCs have direct contact with ___. What “type” of HScs does this niche contain/
direct contact with HScs. contains quiescent HSCs– they have a long term ability to self renew and maintain stem cell population
How is the endosteal niche regulated?
the number of osteoblasts directly corerlate with the number of quiescnet HSCs in the endosteal niche.
Osteoblasts secrete angiopoietin-1 and thrombopoietin which promotes the cells to remain in quiescent state for a long period of time.
in the endosteal niche that isn’t super super vascularized, how do HSCs get enough oxygen?
the endosteal niche contains microvessels. HSCs can detect changes in O2 content and uses it as a cue for assessing where blood vessels are.
in the perivascular nich, the HSCs have direct contact with ___ and __ cells in blood vessels. What “type “ of HScs does this niche contain?
direct contact with stomal and endothelial cells of blood vessels.
contains active HSCs that divide rapidly and holds more progenitor cells.
in the perivascular niche, ___ is expressed by both endothelial and stomal cells, as well as __ cells and ___ cells. This chemokine is bound by HSCs at the ___ receptor and maintains quiesence and retains HSCs in the perivascular region.
in the perivascular niche, CXCL12 is expressed by both endothelial and stomal cells, as well as CAR cells and MESENCHYME cells. This chemokine is bound by HSCs at the CXCL4 receptor and maintains quiesence and retains HSCs in the perivascular region.
To retain HSCs in the perivascular region, the surrounding cells secrete CXCL12. When this compound is downregulated, what happens?
loss of CXCL12 in MSCs resuces the number of HSCs. When Carcells/ Mesenchyme cells don’t produce CXCL12, the stem cell enters into the blodo and leaves the bone, often as progenitor cells –> where they further differentiate.
How is CXCL12 secretion by cells in the perivascular niche regulated by the circadian rhythym.
There is more division and maintenance of HSCs at night, indicating that there is more CXCL12 being produced by CAR/endothelial/stromal/mesenchyme cells in the perivascular region at night.
- there is more migration of progenitor cells at the day. This indicates that there is less CXCL12 being produced in the day since the HSCs can enter the blood and leave the bone/differentiate.
- this is due to NE innervation. NE increases= CXCL12 down regulation, allowing HSC progenitor cells to circulate. too much stress = les and less CXCL12 = less stem cell proliferation.
WHat neurotransmitter is responsible for CXCL12 downregulation
NE. more NE = more CXCL12
Mesenchymal stem cells (MSCs) are aka
bone marrow-derived stem cells (BMDCs)
BMDCs, aka MSCs, resemble ___ morphologically
resemble fibroblasts.
list 3 paracrine factors that can aid in the regulation/differentiation of MSCs
1) Platelet derived growth factor (PDGF): involved in FAT and CHONDROCYTE formation
2) TGFBeta: also required for chondrogenesis
3) Fibroblast growth factor (FGF): involved in bone cell differentiation.
therefore, paracrine factors appear to detect development of the MSC into specific lineages.