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  • 1
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    Hoxb5 marks long-term haematopoietic stem cells and reveals a homogenous perivascular niche (2016)
    Nature Publishing Group (NPG)
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    Publication Date: 2016-02-13
    Description: Haematopoietic stem cells (HSCs) are arguably the most extensively characterized tissue stem cells. Since the identification of HSCs by prospective isolation, complex multi-parameter flow cytometric isolation of phenotypic subsets has facilitated studies on many aspects of HSC biology, including self-renewal, differentiation, ageing, niche, and diversity. Here we demonstrate by unbiased multi-step screening, identification of a single gene, homeobox B5 (Hoxb5, also known as Hox-2.1), with expression in the bone marrow that is limited to long-term (LT)-HSCs in mice. Using a mouse single-colour tri-mCherry reporter driven by endogenous Hoxb5 regulation, we show that only the Hoxb5(+) HSCs exhibit long-term reconstitution capacity after transplantation in primary transplant recipients and, notably, in secondary recipients. Only 7-35% of various previously defined immunophenotypic HSCs are LT-HSCs. Finally, by in situ imaging of mouse bone marrow, we show that 〉94% of LT-HSCs (Hoxb5(+)) are directly attached to VE-cadherin(+) cells, implicating the perivascular space as a near-homogenous location of LT-HSCs.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chen, James Y -- Miyanishi, Masanori -- Wang, Sean K -- Yamazaki, Satoshi -- Sinha, Rahul -- Kao, Kevin S -- Seita, Jun -- Sahoo, Debashis -- Nakauchi, Hiromitsu -- Weissman, Irving L -- F30-HL122096/HL/NHLBI NIH HHS/ -- R01 CA086065/CA/NCI NIH HHS/ -- R01 HL058770/HL/NHLBI NIH HHS/ -- T32 GM007365/GM/NIGMS NIH HHS/ -- U01 HL099999/HL/NHLBI NIH HHS/ -- England -- Nature. 2016 Feb 11;530(7589):223-7. doi: 10.1038/nature16943.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California 94305, USA. ; Ludwig Center for Cancer Stem Cell Research and Medicine, Stanford University School of Medicine, Stanford, California 94305, USA. ; Division of Stem Cell Therapy, Center for Stem Cell Biology and Regenerative Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26863982" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens, CD/metabolism ; Biomarkers/analysis ; Bone Marrow/metabolism ; Cadherins/metabolism ; Cell Self Renewal ; Gene Expression Regulation ; Genes, Reporter/genetics ; Hematopoietic Stem Cell Transplantation ; Hematopoietic Stem Cells/*cytology/*metabolism ; Homeodomain Proteins/genetics/*metabolism ; Immunophenotyping ; Male ; Mice ; Mice, Inbred C57BL ; *Stem Cell Niche
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 2
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    Epigenetic memory in induced pluripotent stem cells (2010)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2010-07-21
    Description: Somatic cell nuclear transfer and transcription-factor-based reprogramming revert adult cells to an embryonic state, and yield pluripotent stem cells that can generate all tissues. Through different mechanisms and kinetics, these two reprogramming methods reset genomic methylation, an epigenetic modification of DNA that influences gene expression, leading us to hypothesize that the resulting pluripotent stem cells might have different properties. Here we observe that low-passage induced pluripotent stem cells (iPSCs) derived by factor-based reprogramming of adult murine tissues harbour residual DNA methylation signatures characteristic of their somatic tissue of origin, which favours their differentiation along lineages related to the donor cell, while restricting alternative cell fates. Such an 'epigenetic memory' of the donor tissue could be reset by differentiation and serial reprogramming, or by treatment of iPSCs with chromatin-modifying drugs. In contrast, the differentiation and methylation of nuclear-transfer-derived pluripotent stem cells were more similar to classical embryonic stem cells than were iPSCs. Our data indicate that nuclear transfer is more effective at establishing the ground state of pluripotency than factor-based reprogramming, which can leave an epigenetic memory of the tissue of origin that may influence efforts at directed differentiation for applications in disease modelling or treatment.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3150836/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3150836/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kim, K -- Doi, A -- Wen, B -- Ng, K -- Zhao, R -- Cahan, P -- Kim, J -- Aryee, M J -- Ji, H -- Ehrlich, L I R -- Yabuuchi, A -- Takeuchi, A -- Cunniff, K C -- Hongguang, H -- McKinney-Freeman, S -- Naveiras, O -- Yoon, T J -- Irizarry, R A -- Jung, N -- Seita, J -- Hanna, J -- Murakami, P -- Jaenisch, R -- Weissleder, R -- Orkin, S H -- Weissman, I L -- Feinberg, A P -- Daley, G Q -- CA86065/CA/NCI NIH HHS/ -- DP1 OD000256/OD/NIH HHS/ -- DP1 OD000256-01/OD/NIH HHS/ -- HL099999/HL/NHLBI NIH HHS/ -- K99 HL093212/HL/NHLBI NIH HHS/ -- K99 HL093212-01/HL/NHLBI NIH HHS/ -- K99 HL093212-02/HL/NHLBI NIH HHS/ -- K99HL093212-01/HL/NHLBI NIH HHS/ -- P50HG003233/HG/NHGRI NIH HHS/ -- R01 CA086065/CA/NCI NIH HHS/ -- R01 DK059279/DK/NIDDK NIH HHS/ -- R01 DK059279-02/DK/NIDDK NIH HHS/ -- R01 DK059279-10/DK/NIDDK NIH HHS/ -- R01 DK070055/DK/NIDDK NIH HHS/ -- R01 DK070055-01/DK/NIDDK NIH HHS/ -- R01 GM083084/GM/NIGMS NIH HHS/ -- R01 GM083084-04/GM/NIGMS NIH HHS/ -- R01-DK59279/DK/NIDDK NIH HHS/ -- R01-DK70055/DK/NIDDK NIH HHS/ -- R01AI047457/AI/NIAID NIH HHS/ -- R01AI047458/AI/NIAID NIH HHS/ -- R37 HD045022/HD/NICHD NIH HHS/ -- R37CA054358/CA/NCI NIH HHS/ -- RC2 HL102815/HL/NHLBI NIH HHS/ -- RC2 HL102815-01/HL/NHLBI NIH HHS/ -- RC2-HL102815/HL/NHLBI NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2010 Sep 16;467(7313):285-90. doi: 10.1038/nature09342.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Stem Cell Transplantation Program, Division of Pediatric Hematology/Oncology, Manton Center for Orphan Disease Research, Howard Hughes Medical Institute, Children's Hospital Boston and Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20644535" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Differentiation/genetics ; Cell Lineage/genetics ; Cellular Reprogramming/genetics ; DNA Methylation/genetics ; Embryonic Stem Cells/cytology/metabolism ; *Epigenesis, Genetic ; Genome/genetics ; Hematopoietic Stem Cells/cytology/metabolism ; Induced Pluripotent Stem Cells/*cytology/*metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Inbred CBA ; Nuclear Transfer Techniques ; Transcription Factors/genetics/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
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