Osteoblasts (OBs) are indispensable for the maintenance of hematopoietic stem cells (HSCs) in the bone marrow microenvironment. Here we investigated how Smad4 modulates HSC fate at distinct stages of OB development. For this, we conditionally knocked out Smad4 in cells expressing type I collagen (Col1a1) and osteocalcin (OC), respectively. Col1a1-expressing OBs were widely present in both the trabecular and cortical compartment, whereas OC-expressing OBs were predominantly located in the cortical compartment. HSCs from Col1a1 mutants displayed senescence-associated phenotypes. OC mutants did not exhibit HSC senescence-related phenotypes, but instead showed preferential HSC death. Of note, stromal cell-derived factor 1 expression was lower in Col1a1 mutants than control littermates, suggesting potential impairment of CXCR4-CXCL12-mediated HSC retention. Disruption of the CXCR4-CXCL12 axis by AMD3100 administration led to an increase in the senescence-associated β-galactosidase activity and low competitive potential. Collectively, our findings indicate that deletion of Smad4 in OBs differentially modulates HSC fate in a stage-dependent manner.
In this study the control of interfacial layers in nanometre thin Ga x In 1−x As/InP heterostructures is demonstrated by variation of the growth interruption sequence (GIS) at the binary-ternary interfaces. All samples have been prepared by chemical beam epitaxy simultaneously growing the structures on exact (100) substrates and (100) substrates misoriented by 2 • towards (110). Characterization was by means of photoluminescence (PL) spectroscopy and high-resolution x-ray diffraction. It is shown that both composition and thickness of the interfacial layers can be manipulated on the (sub)monolayer scale with GIS times of the order of seconds. According to analysis of the x-ray data, interfaces can be tuned from +4 × 10 −3 compression to −4 × 10 −3 tension around nominally lattice-matched Ga x In 1−x As quantum wells of six monolayers thick. The PL investigations show that the tensile Ga x In 1−x P interfaces have no effect on the position of the PL peak maximum whereas compressive, InAs-like interfaces shift the transition to lower energy. This trend can be qualitatively understood but for all samples the calculated transition energies are higher than the measured values. Recommendations are given for further work which is not only of importance to the InP/Ga x In 1−x As system but should be applicable to quantum well structures in other materials where heterojunctions involve changes in both the group V and group III sublattices.
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