Moraga Biotech Blog

Moraga Biotech Blog http://moragabiotech.com/nucleus/ en-us Nucleus CMS v3.23 © Weblog http://backend.userland.com/rss http://moragabiotech.com/nucleus//nucleus/nucleus2.gif Moraga Biotech Blog http://moragabiotech.com/nucleus/ Impaired Bone Development and Increased Mesenchymnal Progenitor Cells in Calvaria of RB1-/- Mice http://moragabiotech.com/nucleus/index.php?itemid=594 reported the results of their study showing involvement of the retinoblastoma protein (pRb) during osteogenesis. The researchers noted that in primary RB1-/- calvarial cells, there is an increase of the osteoprogenitor pool. In conditional knock-out RB1 mice, the animals displayed a developmental defect in bones, paritcularly in the calvaria. It was shown that cultured RB1-/- calvarial osteoblast continued to proliferate after reaching confluence. The osteoblasts undergoing differentiation showed "a clear adipogenic ability with increased multipotency." The investigators also note that RB1`-/- osteoblasts had very low levels of mRNAs expressed during the late stages of differentiation. The authors concluded that their study "presented strong evidence that pRb has multiple regulatory roles in osteogenesis." Additionally, it was noted that pRb deficiency leads to an expanded pool of osteoprogenitors cells which "may be susceptible to additional transforming events leading to osteosarcoma. ]]> Stem Cell Genes and Regulation http://moragabiotech.com/nucleus/index.php?itemid=594 Thu, 20 Nov 2008 10:44:28 -0700 Exercise Enhances Proliferation of Neural Stem Cells and Survival of Neuronal Progenitor Cells in Hippocampus of Middle-Aged Mice http://moragabiotech.com/nucleus/index.php?itemid=593 published in the November issue of J. of Applied Physiology their study results on the effects of exercise on middle-aged mice. The study involved 3 month-old and middle-aged mice running on a treadmill and its effects on neurogenesis and the survival of neuronal progenitor cells in the dentate gyrus of the hippocampus. Without exercise, the study data showed that there was a dramatic decrease in the number of mitotic cells and neuronal progenitors in the dentate gyrus in the brains of middle-aged animals. After 5 weeks of treadmill running, the experimental results revealed that there was an increase in proliferation of neural stem cells in the number of immature neurons in the hippocampus in the older mice. The investigators also noted that exercise enhanced survival of immature neurons in middle-aged mice. The researchers provided data showing that 5 weeks of exercise restored age-dependent decline of bran-derived neurotrophic factor and its receptor, TrkB, "which are known to promote neuronal differentiation and survival." The authors concluded that "taken together, mandatory running exercise alters the brain chemistries of middle-aged animals toward an environment that is favorable to neural stem cell proliferation, survival, and maturation."
]]> General http://moragabiotech.com/nucleus/index.php?itemid=593 Tue, 18 Nov 2008 12:20:27 -0700 Regulation of Human Multipotent Stromal Cell Differentiation and LIF Expression by microRNA http://moragabiotech.com/nucleus/index.php?itemid=592 reported in the November 14th online edition of PNAS, their findings in the regulation of bone marrow-derived human multipotent stromal cells (hMSCs) differentiation by microRNA. Initially, the investigators found that they could inhibit hMSCs differentiation into osteoblasts and adipocytes by lentiviruses expressing shRNA which inhibit Dicer and Drosha. Gene expression analysis revealed that 19 miRNAs were upregulated during osteogenesis and adipogenesis. With in silico modeling, the researchers found that 11 miRNAs targeted those genes in regulating osteogenic and adipogenic differentiation of hMSCs. The study results also demonstrated that two miRMAS, hsa-mir199a and hsa-mir346, targetd leukemia inhibitroy factor (LIF) expression and reduced LIF secretion by hMSCs. The authors concluded that their "results demonstrate that differentiation of hMSCs is regulated by miRNAs and that several of these miRNAS target LIF."]]> Stem Cell Genes and Regulation http://moragabiotech.com/nucleus/index.php?itemid=592 Mon, 17 Nov 2008 10:45:00 -0700 Activation of Wnt/β-Catenin Signaling Enhances Reprogramming of Somatic Cells Mediated by Cell Fusion http://moragabiotech.com/nucleus/index.php?itemid=591 reported in the November 6th online edition of Cell Stem Cell their ability to reprogram cells by cell fusion of embryonic stem cells (ESCs) with somatic cells. The researchers periodically activated the Wnt/β-catenin in ESCs with a small molecule 6-bromoindirubin-3'-oxime (BIO)---an inhibitor of glycogen synthase kinase-3 (GSK-3). The experimental data revealed that accumulation of β-catenin in the ESCs enhanced reprogramming of the fused cells in a dose-dependent manner. It was found that the reprogrammed clones lost their somatic cell differentiation markers concomitant with demethylation at the Oct4 and Nanog CpG islands. The investigators also demonstrated that the reprogrammed fused cells were able to differentiate into cardiomyocytes in vitro and generate teratomas in vivo. The authors concluded that periodic β-catenin accumulation in ESCs "provides a specific threshold that leads to the reprogramming of somatic cells after fusion."]]> Signaling and Pathways http://moragabiotech.com/nucleus/index.php?itemid=591 Fri, 14 Nov 2008 15:04:20 -0700 BCR-ABl-transformed GMP as Myeloid Leukemic Stem Cells http://moragabiotech.com/nucleus/index.php?itemid=590 sts from the Univ. of California, San Diego, Y. Minami et al., reported in the November 11th online edition of PNAS the ability to generate leukemic stem cells (leukemia-initiating cells) by transforming mouse hematopoietic stem cells (mHSCs) with p210^BCR-ABL. These bone marrow-derived cells from E2A knock-out mice retained their pluripotency in ex vivo culture. Transplantation of the transformed cells into cogenic mice recapitulated chronic myelogenous leukemia in the recipient mice. More importantly, the leukemia-initiating cells were found in the granulocyte macrophage progenitor (GMP) compartment of the bone marrow. Additionally, the leukemogenic GMP displayed higher levels of nuclear β-catenin activity than the non-transformed GMP. Restoration of E2A function did not reverse the BCR-ABL-induced transformation. The authors concluded that their "results provide further evidence that BCR-ABL-transformed GMP with abnormal β-catenin activity can function as leukemic stem cells."]]> Stem Cells and Cancer http://moragabiotech.com/nucleus/index.php?itemid=590 Thu, 13 Nov 2008 22:21:00 -0700 Multipotent Stem Cells Derived from War-Traumatized Muscle Tissue http://moragabiotech.com/nucleus/index.php?itemid=589 reported in the November 1st issue of J. of Bone and Joint Surgery their ability to isolate multipotent mesenchymal progenitor cells from muscle tissue debrided from the injury site of soldiers wounded during combat. Mesenchymal stem cells (MSCs) were harvested from enzymatically digested muscle tissue, enriched, and expanded in culture. The isolated mesenchymal progenitor cells stained positive for the surface markers CD73, CD90, and CD105. In vitro differentiation with specific inductive factors demonstrated osteogenesis, adipogenesis, and chrondrogenesis. RT- PCR analysis confirmed multilineage mesenchymal differentiation at the gene expression level. The authors concluded that their study's results suggest that MSCs isolated from war-traumatized tissues have the potential for applications in cell-based tissue engineering for treating musculoskeletal trauma.
]]> Isolation and Characterization http://moragabiotech.com/nucleus/index.php?itemid=589 Tue, 11 Nov 2008 23:00:44 -0700 Sox2 Silencing in Glioblastoma Cancer Stem Cells Causes Loss of Tumorigenicity http://moragabiotech.com/nucleus/index.php?itemid=587 reported in the November 6th online edition of Stem Cells, a new therapeutic approach in targeting cancer stem cells in a highly aggressive cerebral tumor, glioblastoma. With gene silencing techniques, the investigators targeted Sox2, the master gene for self-renewal in neural stem cells. The researchers silenced Sox2 expression in tumor initiating cells (TICs)/cancer stem cells isolated from primary glioblastoma tumors. After implantation into immunodeficient mice, the experimental results revealed that the TICs stopped proliferating concomitant with losing their tumorigenicity. The authors concluded that their experimental results suggest that Sox2 is important for the maintenance of self-renewal not only in neural stem cells but also in those stem cells which had been transformed. The authors also concluded that" Sox2 or its immediate downstream effectors, would...be an ideal target for glioblastoma therapy."

]]> Stem Cells and Cancer http://moragabiotech.com/nucleus/index.php?itemid=587 Mon, 10 Nov 2008 20:03:00 -0700 A Questionable NMR Biomarker for Neural Progenitor Cells http://moragabiotech.com/nucleus/index.php?itemid=588 published the results of their study on using nuclear magnetic resonance (NMR) spectroscopic imaging to assay for neural progenitor cells and neurogenesis in vivo and in vitro. The investigators raised the question in their report in the November 6th online edition of Stem Cells, whether the lipid signal at 1.28 ppm of the NMR spectra were specifically attributed to neural progenitor cells (NPCs). The experimental results revealed that 1.28 ppm is reflected in NPC cultures but not in vivo in known neurogenic regions of the brain. The researchers noted that mesenchymal stem cells and non-stem cell lines also possess the 1.28 ppm biomarker. Additionally, the biomarker is absent from freshly isolated NPCs and they appreared to be expressed in cells undergoing growth arrest or apoptosis. It was noted that this condition favors the appearance of mobile microlipid droplets. The authors concluded that their study supports the need to identify additional biomarkers are in order to determine the presence of NPCs and neurogenesis both in vivo and in vitro.]]> General http://moragabiotech.com/nucleus/index.php?itemid=588 Mon, 10 Nov 2008 11:26:00 -0700 Small Molecule Induction of Pluripotent Stem Cells from Mouse Embryonic Fibroblasts Transfected with Oct4 and Klf4 http://moragabiotech.com/nucleus/index.php?itemid=586 published in the November 6th issue of Celll Stem Cells, their study on reprogramming mouse embryonic fibroblasts by transduction of two transcription factors Oct4 and Klf4 and two small molecules, BIX-01294 and BayK8644. The study was based upon a previous finding that neural progenitor cells endogenously expressed Sox2. With a cell-based high-throughput screening of small molecules, the investigators found two small molecules BIX and BayK that could reprogram mouse embryonic fibroblasts into induced pluripotent stem (iPS) cells. These embryonic fibroblasts had been transfected with Oct4 and Klf4 prior to being exposed to the two compounds. BIX is an inhibitor of enzymes involved in the regulation of gene expression which enables reprogramming of fibroblasts in the absence of Sox2 overexpression. BayK is a calcium channel agonist which enhances the reprogramming efficiency of BIX and in the absence of BIX there was no observable reprogramming of the transduced cells. The experimental results suggest that BayK appeared to enhance the effect of BIX. The researchers found that there was a significant increase in the number of iPS cells resulting from exposure to both small molecules compared to transduced cells treated with BIX. The authors concluded that their study revealed that small molecules can compensate for viral transduction of critical transcription factors as well as improve the reprogramming efficiency.
]]> Stem Cell Genes and Regulation http://moragabiotech.com/nucleus/index.php?itemid=586 Fri, 7 Nov 2008 14:16:00 -0700 Induction of Pluripotent Stem Cells from Primary Human Fibroblasts with only Oct4 and Sox2 http://moragabiotech.com/nucleus/index.php?itemid=585 reported in the October 12th online edition of Nature Biotechnology their findings to induce pluripotent stem (iPS) cells using only two transcription factors, Oct4 and Sox2. Reprogramming of somatic cells usually require transfection of the oncogenes c-Myc and Klf4 as well as the above transcription factors. The investigators found that by using the histone deacetylase inhibitor, valproic acid, they were able to reprogram primary human fibroblasts without c-Myc and Klf4. The experimental results showed that the human iPS cells induced by the two transcription factor resemble human embyronic cells in their pluripotency, gene expression profiles and epigenetic states. The authors concluded that their technique for reprogramming human somatic cells by purely chemical means "would make therapeutic use of reprogrammed cells safer and more practical."]]> Stem Cell Genes and Regulation http://moragabiotech.com/nucleus/index.php?itemid=585 Thu, 6 Nov 2008 08:51:00 -0700