Notch signaling and the bone marrow hematopoietic stem cell niche

University of Rochester, Rochester, New York, United States
Bone (Impact Factor: 4.46). 09/2009; 46(2):281-5. DOI: 10.1016/j.bone.2009.08.007
Source: PubMed

ABSTRACT Recently there has been increased interest in the regulatory interactions between osteoblasts and cells in the surrounding bone marrow microenvironment. The proximity of hematopoietic stem cells (HSCs) with osteoblastic cells first suggested regulatory interactions, and recent data have highlighted the role of osteoblastic cells in providing a HSC niche. Reports have indicated that direct contact is necessary to mediate the osteoblastic effects and that these effects could be mediated through Notch activation. Notch signaling is important throughout development and also appears to play a critical role in cellular maturation and differentiation of osteoblastic cells and hematopoietic cells as disregulation can lead to bone loss and leukemias, respectively. In this review we discuss the current understanding of Notch signaling and how it functions in hematopoiesis, osteoblastic cells, and the interactions between HSC and their osteoblastic niche.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Based on the design oriented time domain and frequency analysis of the lumped model of power distribution network (PDN) involving high performance microprocessor core, packaging, PCB and power source, this paper presents simple design equations to realize the critically damped transient response at the microprocessor load. In order to realize the critically damped PDN with flat output impedance magnitude, a systematic method of sizing the decoupling capacitors to be used in the distributed model of PDN is described. Simulation results are presented, verifying the validity of the systematic design methodology.
    Electrical Performance of Electronic Packaging, 2002; 02/2002
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: In mobile ad hoc network (MANET) studies, it is imperative to use highly detailed device models as they provide high layer protocols with good prediction of underlying wireless communication performance. However, such studies often utilize abstract models for execution speed and simplicity. This paper first shows that physical layer variables including path loss, shadowing, multipath, Doppler have significant effects on the predicted overall networking performance. It then proposes an approach to simulate details of wireless propagation and radio characteristics in networking studies while still maintaining a reasonable simulation execution time. Through our runtime performance studies with detailed OFDM Simulink/MATLAB models and QualNet network simulator, it is shown that the proposed approach can improve the simulation runtime performance by three to four orders of magnitudes without compromising the fidelity of simulation results.
    Parallel and Distributed Simulation, 2004. PADS 2004. 18th Workshop on; 06/2004
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Notch receptors are transmembrane receptors that regulate cell fate decisions. There are four Notch receptors in mammals. Upon binding to members of the Delta and Jagged family of transmembrane proteins, Notch is cleaved and the Notch intracellular domain (NICD) is released. NICD then translocates to the nucleus, where it associates with the CBF-1, Suppressor of Hairless, and Lag-2 (CSL) and Mastermind-Like (MAML) proteins. This complex activates the transcription of Notch target genes, such as Hairy Enhancer of Split (Hes) and Hes-related with YRPF motif (Hey). Notch signaling is critical for the regulation of mesenchymal stem cell differentiation. Misexpression of Notch in skeletal tissue indicates a role as an inhibitor of skeletal development and postnatal bone formation. Overexpression of Notch inhibits endochondral bone formation and osteoblastic differentiation, causing severe osteopenia. Conditional inactivation of Notch in the skeleton causes an increase in cancellous bone volume and enhanced osteoblastic differentiation. Notch ligands are expressed in the hematopoietic stem cell niche and are critical for the regulation of hematopoietic stem cell self-renewal. Dysregulation of Notch signaling is the underlying cause of diseases affecting the skeletal tissue, including Alagille syndrome, spondylocostal dysostosis, and possibly, osteosarcoma.
    Molecular and Cellular Biology 12/2009; 30(4):886-96. DOI:10.1128/MCB.01285-09 · 5.04 Impact Factor


Available from