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Unique Multipotent Cells in Adult Human Mesenchymal Cell Populations

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Unique Multipotent Cells in Adult Human Mesenchymal Cell Populations Corrections IN THIS ISSUE BIOCHEMISTRY, CHEMISTRY Correction for “In This Issue,” which appeared in issue 16, April Correction for “Crystal structure of PhnZ in complex with sub- 22, 2014, of Proc Natl Acad Sci USA (111:5755–5756; 10.1073/ strate reveals a di-iron oxygenase mechanism for catabolism iti1614111). of organophosphonates,” by Laura M. van Staalduinen, Fern The authors note that, due to a printer’s error, on page 5755, R. McSorley, Katharina Schiessl, Jacqueline Séguin, Peter B. Wyatt, right column, first paragraph, line 2, “This preference is reflected Friedrich Hammerschmidt, David L. Zechel, and Zongchao Jia, in adult speakers’ more frequent misperceptions of lbif than blif which appeared in issue 14, April 8, 2014, of Proc Natl Acad Sci in psychological experiments and in the prevalence of the former USA (111:5171–5176; first published March 21, 2014; 10.1073/ syllable type across languages” should instead appear as “This pnas.1320039111). preference is reflected in adult speakers’ more frequent mis- The authors note that on page 5175, right column, second full perceptions of lbif than blif in psychological experiments and in paragraph, line 1 “A more complete mechanism can now be the prevalence of the latter syllable type across languages.” proposed for PhnZ. In the resting state, Y24 occupies the O2 Additionally, on page 5756, right column, first full paragraph, binding site of Fe2 (Fig. 5). Upon binding the substrate (R)-2 line 13, “Differences in brain connectivity reflect a biological trait at Fe2, E27 binds to the 2-amino group and triggers the re- rather than a technical artifact, and may lead to revisions of the lease of Y24 from the active site. The expulsion of Y24 may interpretations of imaging data in many neurodevelopmental, also be promoted by an electron transfer from Fe1 to Fe2. according to the authors” should instead appear as “Differences This would allow O2 to bind at Fe2 and be reduced to form a •− in brain connectivity reflect a biological trait rather than a tech- Fe(III)-O2 species, which subsequently abstracts the C1 nical artifact, and may lead to revisions of the interpretations of hydrogen of (R)-2 to initiate CP bond cleavage (17).” should imaging data in many neurodevelopmental studies, according to instead appear as “A more complete mechanism can now be the authors.” The online version has been corrected. proposed for PhnZ. In the resting state, Y24 occupies the O2 binding site of Fe1 (Fig. 5). Upon binding the substrate (R)-2 www.pnas.org/cgi/doi/10.1073/pnas.1408053111 at Fe2, E27 binds to the 2-amino group and triggers the release of Y24 from the active site. The expulsion of Y24 may also be promoted by an electron transfer from Fe2 to Fe1. This would •− allow O2 to bind at Fe1 and be reduced to form a Fe(III)-O2 species, which subsequently abstracts the C1 hydrogen of (R)-2 NEUROSCIENCE to initiate CP bond cleavage (17).” Correction for “PDF and cAMP enhance PER stability in Drosophila clock neurons,” by Yue Li, Fang Guo, James Shen, www.pnas.org/cgi/doi/10.1073/pnas.1408022111 and Michael Rosbash, which appeared in issue 13, April 1, 2014, of Proc Natl Acad Sci USA (111:E1284–E1290; first pub- lished March 18, 2014; 10.1073/pnas.1402562111). The authors note that the reviewer name Patrick Edery should instead appear as Patrick Emery. The online version has been corrected. www.pnas.org/cgi/doi/10.1073/pnas.1408057111 CORRECTIONS www.pnas.org PNAS | June 3, 2014 | vol. 111 | no. 22 | 8311–8312 Downloaded by guest on October 1, 2021 DEVELOPMENTAL BIOLOGY Correction for “Unique multipotent cells in adult human Yoshinori Fujiyoshi, and Mari Dezawa, which appeared in mesenchymal cell populations,” by Yasumasa Kuroda, issue 19, May 11, 2010, of Proc Natl Acad Sci USA Masaaki Kitada, Shohei Wakao, Kouki Nishikawa, Yukihiro (107:8639–8643; first published April 26, 2010; 10.1073/pnas. Tanimura, Hideki Makinoshima, Makoto Goda, Hideo 0911647107). Akashi, Ayumu Inutsuka, Akira Niwa, Taeko Shigemoto, The authors note that Fig. 3 appeared incorrectly. The cor- Yoko Nabeshima, Tatsutoshi Nakahata, Yo-ichi Nabeshima, rected figure and its legend appear below. Fig. 3. Transplantation of Muse cells and M-cluster formation from bone marrow. (A–E) Differentiation of GFP-labeled MEC population (H-fibroblasts) in damaged tissues of immunodeficient mice. (A) Cells locally injected into the edge of the excised region. Transplanted GFP(+) cells expressed cytokeratin 14 (red) in the regenerating epidermis (2 weeks). (B) Two weeks after i.v. injection, GFP(+) cells with central nuclei were seen in cardiotoxin-injected cutaneous muscle. Transplanted GFP(+) cells (arrow) and host cells [GFP(−), arrowhead] that expressed Pax7 were seen. (C) After 4 weeks, the GFP(+) muscle fibers expressed human dystrophin (h-Dystrophin; red). Four weeks after i.v. injection, most of the transplanted GFP(+) cells in liver with CCl4-induced damage were positive for human Golgi complex (D and E, white); some of them expressed human albumin (D, red) or human antitrypsin (E, red). (F–H) Formation of M-clusters from bone marrow-derived mononucleated cells. (F) M-clusters formed with 8-hr LTT (8-hr hBM-MC, day 7). (G) ALP(+) cells in 8-hr hBM-MC (day 7). (H) RT-PCR of naive H-MSCs (Naive 1 and Naive 2); M-clusters formed with 8-hr LTT (8-hr hBM) or without LTT [Naive hBM (N-hBM)]. Positive controls were human fetus liver (Liver) for α-fetoprotein (α-FP) and whole human embryo (Embryo) for GATA6, MAP-2, and Nkx2.5. (Scale bars: A, B, E, F, and G,50μm; C and D, 100 μm.) www.pnas.org/cgi/doi/10.1073/pnas.1408449111 8312 | www.pnas.org Downloaded by guest on October 1, 2021 Unique multipotent cells in adult human mesenchymal cell populations Yasumasa Kurodaa,1, Masaaki Kitadaa,1, Shohei Wakaoa, Kouki Nishikawab, Yukihiro Tanimuraa, Hideki Makinoshimaa, Makoto Godac, Hideo Akashia, Ayumu Inutsukab, Akira Niwad, Taeko Shigemotoa, Yoko Nabeshimae, Tatsutoshi Nakahatad, Yo-ichi Nabeshimae, Yoshinori Fujiyoshib, and Mari Dezawaa,2 aDepartment of Stem Cell Biology and Histology, Graduate School of Medicine, Tohoku University, Sendai 980-8575, Japan; bDepartment of Biophysics, Graduate School of Science, Kyoto University, Kyoto 606-8502, Kyoto, Japan; dCenter for iPS Cell Research and Application, Kyoto University, Kyoto 606-8507, Japan; eDepartment of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan; and cJapan Biological Informatics Consortium (Kyoto Branch Office), Oiwake, Kitashirakawa, Sakyo-ku, Kyoto 606-8502, Japan Edited* by Yoshito Kaziro, Kyoto University, School of Medicine, Kyoto, Japan, and approved March 29, 2010 (received for review October 8, 2009) We found adult human stem cells that can generate, from a single In the present study, we demonstrate, at the single-cell level, cell, cells with the characteristics of the three germ layers. The cells that adult human skin fibroblasts, MSCs, and native bone marrow are stress-tolerant and can be isolated from cultured skin fibroblasts aspirates contain a distinct type of stem cell that is capable of or bone marrow stromal cells, or directly from bone marrow generating cells with characteristics of all three germ layers. These aspirates. These cells can self-renew; form characteristic cell clusters cells are indistinguishable from other major mesenchymal cells in in suspension culture that express a set of genes associated with adherent culture, but when they are transferred to suspension pluripotency; and can differentiate into endodermal, ectodermal, culture, they form characteristic cell clusters that are positive for and mesodermal cells both in vitro and in vivo. When transplanted pluripotency markers and exhibit self-renewal and differentiation. into immunodeficient mice by local or i.v. injection, the cells Furthermore, they can be efficiently isolated as cells positive for integrated into damaged skin, muscle, or liver and differentiated both SSEA-3, a human pluripotency marker, and CD105, a mes- into cytokeratin 14-, dystrophin-, or albumin-positive cells in the enchymal cell marker. The cells exhibit multipotency, but their respective tissues. Furthermore, they can be efficiently isolated as proliferation activity is not very high. Furthermore, although SSEA-3(+) cells. Unlike authentic ES cells, their proliferation activity retaining their differentiation ability in vivo, these cells, unlike is not very high and they do not form teratomas in immunodeficient authentic ES cells, do not form teratomas in testes of immuno- mouse testes. Thus, nontumorigenic stem cells with the ability to deficient mice. Our findings thus suggest that adult human mes- generate the multiple cell types of the three germ layers can be enchymal cell populations, such as skin fibroblasts and MSCs, obtained through easily accessible adult human mesenchymal cells contain distinctly multipotent stem cells and that further studies of without introducing exogenous genes. These unique cells will be these cells will promote a better understanding of mesenchymal beneficial for cell-based therapy and biomedical research. stem cell properties. Collection and enrichment of these cells should contribute to improved differentiation efficiency in mes- bone marrow | differentiation | fibroblasts | mesenchymal stem cell | enchymal cell populations. Finally, because these cells are easily pluripotency accessible, they will be a realistic source of adult human multi- potent stem cells that are capable of differentiation into cells with ecent advances in stem cell research have revealed the exis- characteristics of all three germ layers without the need to in- Rtence of various types of tissue stem cells that contribute to the troduce exogenous genes. These cells thus hold great promise for functional maintenance of organs and to cell renewal, tissue cell-based therapy and biomedical research. remodeling, and repair (1, 2). These stem cells are expected to Results contribute to regenerative medicine, but this will require elucida- Analysis of Cell Clusters Generated from Human Mesenchymal Cells.
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