Cell：Rb参与调控造血干细胞与骨髓微环境的相互作用

生物谷

生物谷报道：血细胞生成主要是由造血干细胞在内外各种刺激信号的作用下介导完成的，其中外界信号刺激主要是来自骨髓微环境。研究已经发现细胞周期调控可以控制干细胞的命运，这是否意味着它是干细胞命运调控的一个内在或是外在效应器呢？最近，研究人员发现了成视网膜母细胞瘤蛋白（Rb），细胞周期中的一个关键蛋白，在血细胞生成中的作用。该研究结果发表在最新一期的《Cell》上。

研究人员发现，鼠类造血系统中的Rb广泛失活会导致严重的骨髓组织增生，造血干细胞则会迁移到髓外组织并分化。这种现象主要源自Rb依赖性的骨髓细胞和微环境的相互作用。

这项研究证实了骨髓微环境对于血细胞生成的顺利进行具有重要的作用，而Rb蛋白则参与了其中的关键调控。

Figure 1. Rapid Mobilization of Primitive Cells into the Peripheral Blood Following Deletion of Rb

(A) Genomic PCR on whole BM from control (Mx⁻pRb^fl/fl) and Rb-deficient animals (Mx⁺pRb^Δ/Δ) at 6 and 12 weeks post-pIpC.

(B) qRT-PCR for pRb, p130, and p107 on cDNA of control and Rb-deficient animals (n = 3 independent samples) 12 weeks post-pIpC.

(C) Platelets and (D) leukocytes in PB following Rb deletion (time 0 = final dose of pIpC); n ≥ 4/time point; ^*p < 0.05.

(E) Day 12 CFU-GEMM and CFU-GM/M from the PB of at 12 weeks post-pIpC; n ≥ 9/genotype; ^*p < 0.01. Value inside bars represents fold increase.

(F) FACS profile and mean number of Lin⁻c-Kit⁺Sca-1⁺ (LKS+) in the PB; n > 4/genotype; ^*p < 0.01. Methylcellulose plates from day 12 of culture. Data expressed as mean ± SEM.

原文出处：

Cell June 15, 2007: 129 (6)

Rb Regulates Interactions between Hematopoietic Stem Cells and Their Bone Marrow Microenvironmentp1081
Carl R. Walkley, Jeremy M. Shea, Natalie A. Sims, Louise E. Purton, and Stuart H. Orkin
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相关基因：

RB1

Official Symbol RB1 and Name: retinoblastoma 1 (including osteosarcoma) [Homo sapiens]
Other Aliases: OSRC, RB
Other Designations: retinoblastoma 1; retinoblastoma susceptibility protein; retinoblastoma suspectibility protein; retinoblastoma-1
Chromosome: 13; Location: 13q14.2
Annotation: Chromosome 13, NC_000013.9 (47775911..47954022)
MIM: 180200
GeneID: 5925

Official Symbol rb and Name: rabbit [Mus musculus]
GeneID: 27313
This record was replaced with GeneID: 13838

作者简介：

Stuart H. Orkin, M.D.

Dr. Orkin, HHMI investigator at Children's Hospital Boston, is also the David G. Nathan Professor of Pediatrics at Harvard Medical School and Chairman of the Department of Pediatric Oncology at the Dana-Farber Cancer Institute. He received his B.S. degree in life sciences from the Massachusetts Institute of Technology and his M.D. degree from Harvard Medical School. His postdoctoral research was performed in Philip Leder's laboratory at the National Institutes of Health. Upon completion of clinical training in pediatrics and hematology-oncology at Children's Hospital Boston, he joined the Harvard faculty. Dr. Orkin's honors include the Mead-Johnson Award, the Dameshek and E. Donnall Thomas Awards of the American Society of Hematology, the Helmut Horten Prize (with Yuet Wai Kan and Sir David Weatherall), and the 2005 Award for Distinguished Research in the Biomedical Sciences from the Association of American Medical Colleges. He is an elected member of the National Academy of Sciences, the Institute of Medicine, and the American Academy of Arts and Sciences.
RESEARCH ABSTRACT SUMMARY:

Stuart Orkin's research focuses on stem cell biology, particularly the development and function of the blood system, the relationship between cancer and stem cells, and the mechanisms responsible for self-renewal of stem cells.

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