Identification of a Distinct Small Cell Population from Human Bone Marrow Reveals Its Multipotency In Vivo and In Vitro
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{"title"=>"Identification of a distinct small cell population from human bone marrow reveals its multipotency in vivo and in vitro", "type"=>"journal", "authors"=>[{"first_name"=>"J", "last_name"=>"Wang"}, {"first_name"=>"X", "last_name"=>"Guo"}, {"first_name"=>"M", "last_name"=>"Lui"}, {"first_name"=>"P J", "last_name"=>"Chu"}, {"first_name"=>"J", "last_name"=>"Yoo"}, {"first_name"=>"M", "last_name"=>"Chang"}, {"first_name"=>"Y", "last_name"=>"Yen"}], "year"=>2014, "source"=>"PLoS One", "identifiers"=>{"issn"=>"1932-6203", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "pmid"=>"24465489", "doi"=>"10.1371/journal.pone.0085112"}, "id"=>"2a8fb96f-f0a8-3837-a40d-cd5c45591922", "abstract"=>"Small stem cells, such as spore-like cells, blastomere-like stem cells (BLSCs), and very-small embryonic-like stem cells (VSELs) have been described in recent studies, although their multipotency in human tissues has not yet been confirmed. Here, we report the discovery of adult multipotent stem cells derived from human bone marrow, which we call StemBios (SB) cells. These isolated SB cells are smaller than 6 im and are DAPI+ and Lgr5+ (Leucine-Rich Repeat Containing G Protein-Coupled Receptor 5). Because Lgr5 has been characterized as a stem cell marker in the intestine, we hypothesized that SB cells may have a similar function. In vivo cell tracking assays confirmed that SB cells give rise to three types of cells, and in vitro studies demonstrated that SB cells cultured in proprietary media are able to grow to 6-25 im in size. Once the SB cells have attached to the wells, they differentiate into different cell lineages upon exposure to specific differentiation media. We are the first to demonstrate that stem cells smaller than 6 im can differentiate both in vivo and in vitro. In the future, we hope that SB cells will be used therapeutically to cure degenerative diseases.", "link"=>"http://www.mendeley.com/research/identification-distinct-small-cell-population-human-bone-marrow-reveals-multipotency-vivo-vitro", "reader_count"=>8, "reader_count_by_academic_status"=>{"Researcher"=>3, "Student > Ph. D. Student"=>3, "Student > Postgraduate"=>1, "Other"=>1}, "reader_count_by_user_role"=>{"Researcher"=>3, "Student > Ph. D. Student"=>3, "Student > Postgraduate"=>1, "Other"=>1}, "reader_count_by_subject_area"=>{"Engineering"=>1, "Materials Science"=>1, "Medicine and Dentistry"=>4, "Agricultural and Biological Sciences"=>1, "Immunology and Microbiology"=>1}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>1}, "Materials Science"=>{"Materials Science"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>4}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>1}}, "reader_count_by_country"=>{"United States"=>1, "United Kingdom"=>1, "France"=>1}, "group_count"=>0}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1349884", "https://ndownloader.figshare.com/files/1349885", "https://ndownloader.figshare.com/files/1349886", "https://ndownloader.figshare.com/files/1349887", "https://ndownloader.figshare.com/files/1349888", "https://ndownloader.figshare.com/files/1349889", "https://ndownloader.figshare.com/files/1349890"], "description"=>"<div><p>Small stem cells, such as spore-like cells, blastomere-like stem cells (BLSCs), and very-small embryonic-like stem cells (VSELs) have been described in recent studies, although their multipotency in human tissues has not yet been confirmed. Here, we report the discovery of adult multipotent stem cells derived from human bone marrow, which we call <b>S</b>tem<b>B</b>ios (SB) cells. These isolated SB cells are smaller than 6 ìm and are DAPI+ and Lgr5+ (Leucine-Rich Repeat Containing G Protein-Coupled Receptor 5). Because Lgr5 has been characterized as a stem cell marker in the intestine, we hypothesized that SB cells may have a similar function. <i>In vivo</i> cell tracking assays confirmed that SB cells give rise to three types of cells, and <i>in vitro</i> studies demonstrated that SB cells cultured in proprietary media are able to grow to 6–25 ìm in size. Once the SB cells have attached to the wells, they differentiate into different cell lineages upon exposure to specific differentiation media. We are the first to demonstrate that stem cells smaller than 6 ìm can differentiate both <i>in vivo</i> and <i>in vitro</i>. In the future, we hope that SB cells will be used therapeutically to cure degenerative diseases.</p></div>", "links"=>[], "tags"=>["developmental biology", "stem cells", "Adult stem cells", "Embryonic stem cells", "Cell differentiation", "Cell fate determination", "Molecular cell biology", "Cellular types", "hematology", "Bone marrow and stem cell transplantation", "marrow", "reveals", "multipotency"], "article_id"=>902921, "categories"=>["Biological Sciences", "Medicine"], "users"=>["James Wang", "Xiaoyu Guo", "Monica Lui", "Pei-Ju Chu", "Jennifer Yoo", "Megan Chang", "Yun Yen"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0085112.s001", "https://dx.doi.org/10.1371/journal.pone.0085112.s002", "https://dx.doi.org/10.1371/journal.pone.0085112.s003", "https://dx.doi.org/10.1371/journal.pone.0085112.s004", "https://dx.doi.org/10.1371/journal.pone.0085112.s005", "https://dx.doi.org/10.1371/journal.pone.0085112.s006", "https://dx.doi.org/10.1371/journal.pone.0085112.s007"], "stats"=>{"downloads"=>12, "page_views"=>24, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Identification_of_a_Distinct_Small_Cell_Population_from_Human_Bone_Marrow_Reveals_Its_Multipotency_In_Vivo_and_In_Vitro_/902921", "title"=>"Identification of a Distinct Small Cell Population from Human Bone Marrow Reveals Its Multipotency <i>In Vivo</i> and <i>In Vitro</i>", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2014-01-17 02:44:32"}
  • {"files"=>["https://ndownloader.figshare.com/files/1349857"], "description"=>"<p><b>A) SB cell attachment.</b> Purified Lgr5+ cells at day 0 (left) and after attachment (right). <b>B) Mesoderm differentiation.</b> Before (left) and after (right) Oil Red O staining for differentiated adipocytes. <b>C) Quantification of Oil Red O- stained cells.</b> Negative controls: SB cells cultured in adipogenesis medium only and SB cells cultured in Stem Pro 34 medium, which is not an adipocyte differentiation media. <b>D) Endoderm differentiation.</b> RT-PCR assay for hepatocyte formation; “-” indicates the negative controls without template cDNA. Expected product sizes: GAPDH (2), 184 bp; albumin, 152 bp; FoxA2, 164 bp; and alpha-fetoprotein, 272 bp. <b>E) Ectoderm differentiation.</b> RT-PCR assay for differentiated neurons; “-” indicates negative controls without template cDNA. Expected product sizes: GAPDH (2), 184 bp; MAPT, 235 bp; and NEFL (neurofilament), 184 bp. Note: * indicates P≤0.01. <b>F) Immunocytochemistry using neurofilament (Cyc-3) staining.</b> Filters (left to right): red (Cyc-3), UV (DAPI), FITC (background), and merged Cyc-3 + DAPI. All scale bars, 100 µm.</p>", "links"=>[], "tags"=>["developmental biology", "stem cells", "Adult stem cells", "Embryonic stem cells", "Cell differentiation", "Cell fate determination", "Molecular cell biology", "Cellular types", "hematology", "Bone marrow and stem cell transplantation", "sb", "cells", "differentiate"], "article_id"=>902901, "categories"=>["Biological Sciences", "Medicine"], "users"=>["James Wang", "Xiaoyu Guo", "Monica Lui", "Pei-Ju Chu", "Jennifer Yoo", "Megan Chang", "Yun Yen"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0085112.g003", "stats"=>{"downloads"=>2, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_hBM_derived_SB_cells_differentiate_in_vitro_/902901", "title"=>"hBM-derived SB cells differentiate <i>in vitro</i>.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-01-17 02:44:32"}
  • {"files"=>["https://ndownloader.figshare.com/files/1349877"], "description"=>"<p>Mouse organs were collected 2 months post-injection. For each tissue, the SB cell-injected mice were compared with the PBS-injected mice. Marker: 100-bp DNA ladder. Expected sizes: beta-actin, 160 bp; Tau, 235 bp; α1-anti-trypsin, 175 bp; and myogenic factor 4, 225 bp.</p>", "links"=>[], "tags"=>["developmental biology", "stem cells", "Adult stem cells", "Embryonic stem cells", "Cell differentiation", "Cell fate determination", "Molecular cell biology", "Cellular types", "hematology", "Bone marrow and stem cell transplantation", "hbm-derived", "sb", "differentiation"], "article_id"=>902914, "categories"=>["Biological Sciences", "Medicine"], "users"=>["James Wang", "Xiaoyu Guo", "Monica Lui", "Pei-Ju Chu", "Jennifer Yoo", "Megan Chang", "Yun Yen"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0085112.g005", "stats"=>{"downloads"=>0, "page_views"=>19, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Xenografts_of_hBM_derived_SB_cell_differentiation_in_vivo_RT_PCR_/902914", "title"=>"Xenografts of hBM-derived SB cell differentiation <i>in vivo</i>: RT-PCR.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-01-17 02:44:32"}
  • {"files"=>["https://ndownloader.figshare.com/files/1349852"], "description"=>"<p><b>A) Presence of SB cells and DAPI staining.</b> The SB cells in the SB mixture layer were visualized under a light microscope. The cells of the SB mixture are shown under white light (left) and UV (middle). The merged image (right) reveals SB cells with a size of approximately 3.5 µm. The SB cells are the only nucleated cells in the SB mixture; thus, the SB cell count is equivalent to the number of DAPI+ cells. Scale bars, 20 µm. <b>B) Annexin-V staining.</b> The SB cells were analyzed for the expression of Annexin-V (black), a marker of apoptotic bodies, and for the isotype control (red). As shown, 99.7% of these cells did not express Annexin-V, indicating that these cells were not apoptotic bodies. <b>C) FISH and DAPI staining of SB cells in the 5-µm transwell assay.</b> Male SB cells were seeded at the top of the transwell, and stromal cells from female bone marrow were seeded at the bottom. FISH staining was performed immediately after the SB cells passed through the 5-µm filter. The SB and stromal cells were both DAPI-positive, but only the SB cells contained the Y-chromosome. Thus, the SB cells were double-positive for nuclear and Y-chromosome staining. One FISH-positive cell (top left) and two DAPI-positive cells (bottom left) are shown. The merged image (bottom right) reveals that the FISH-positive cell was also DAPI-positive, indicating that it is an SB cell. Scale bars, 100 µm.</p>", "links"=>[], "tags"=>["developmental biology", "stem cells", "Adult stem cells", "Embryonic stem cells", "Cell differentiation", "Cell fate determination", "Molecular cell biology", "Cellular types", "hematology", "Bone marrow and stem cell transplantation", "cells"], "article_id"=>902896, "categories"=>["Biological Sciences", "Medicine"], "users"=>["James Wang", "Xiaoyu Guo", "Monica Lui", "Pei-Ju Chu", "Jennifer Yoo", "Megan Chang", "Yun Yen"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0085112.g001", "stats"=>{"downloads"=>0, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_SB_cells_in_hBM_/902896", "title"=>"SB cells in hBM.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-01-17 02:44:32"}
  • {"files"=>["https://ndownloader.figshare.com/files/1349855"], "description"=>"<p><b>A) Flow cytometry of the SB mixture.</b> Beads were purchased from Spherotech, Inc. and examined by flow cytometry to determine the size range standards (a). Using these ranges as a reference, the SB cells were estimated to be 2–6 µm in diameter. Flow cytometry for the hPB and hBM samples before separation (b) and the layer containing only the SB mixture after separation (d). The addition of red blood cell (RBC) lysis buffer revealed that G6 contained RBCs (c). G1 gating represents the background of the staining buffer (e). G2 gating contained particles that were <1 µm in size; most of these were microparticles and microvesicles. G3 contained three major populations (>1 µm): SB cells (G4), RBCs (G6), and white blood cells (WBCs) (G5). The WBCs (G5) were larger than 6–7 µm and have nuclei. <b>B) Flow cytometry of the SB cells.</b> The G4 region was further divided into P1 and P2. (a) P1 gating represents the platelet population. Nearly all of the cells in this gate were CD9+. (b) P2 gating represents the SB cells. We found that 68.3% of these cells were SYTO+, indicating chromosome structure. (c) Lgr5, a stem cell marker, was expressed by 32% of the P2 population. Black: staining with Lgr5; red: staining with the isotype control. <b>C) Flow cytometry of RBCs in the SB cell mixture.</b> G6 represents the RBC location. The RBCs were CD235a+. <b>D) Flow Cytometry of VSELs and BLSCs in the SB cell mixture.</b> Few cells expressed CD66e, a marker of BLSCs (left) and CD133, a marker of VSELs (right), in the SB mixture.</p>", "links"=>[], "tags"=>["developmental biology", "stem cells", "Adult stem cells", "Embryonic stem cells", "Cell differentiation", "Cell fate determination", "Molecular cell biology", "Cellular types", "hematology", "Bone marrow and stem cell transplantation", "sb"], "article_id"=>902899, "categories"=>["Biological Sciences", "Medicine"], "users"=>["James Wang", "Xiaoyu Guo", "Monica Lui", "Pei-Ju Chu", "Jennifer Yoo", "Megan Chang", "Yun Yen"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0085112.g002", "stats"=>{"downloads"=>0, "page_views"=>19, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Distinct_SB_cell_markers_/902899", "title"=>"Distinct SB cell markers.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-01-17 02:44:32"}
  • {"files"=>["https://ndownloader.figshare.com/files/1349876"], "description"=>"<p>Mouse organs were collected 2 months post-injection. For each tissue, the SB cell-injected mice (top rows) were compared with the PBS injected-mice (bottom row). The human Y-chromosome Cyc-3 probe was used for FISH staining. The sections were also counterstained with DAPI. Filters: merged Cyc-3 + UV, red (Cyc-3), UV (DAPI), and FITC (background) for top row and red (Cyc-3), UV (DAPI), and FITC (background) and merged Cyc-3 + UV for bottom row. Scale bars, 50 µm.</p>", "links"=>[], "tags"=>["developmental biology", "stem cells", "Adult stem cells", "Embryonic stem cells", "Cell differentiation", "Cell fate determination", "Molecular cell biology", "Cellular types", "hematology", "Bone marrow and stem cell transplantation", "sb", "cells", "xenograft", "staining"], "article_id"=>902913, "categories"=>["Biological Sciences", "Medicine"], "users"=>["James Wang", "Xiaoyu Guo", "Monica Lui", "Pei-Ju Chu", "Jennifer Yoo", "Megan Chang", "Yun Yen"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0085112.g004", "stats"=>{"downloads"=>3, "page_views"=>21, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_hBM_derived_SB_cells_in_a_mouse_xenograft_model_FISH_staining_of_mouse_tissue_sections_/902913", "title"=>"hBM-derived SB cells in a mouse xenograft model: FISH staining of mouse tissue sections.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-01-17 02:44:32"}

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Relative Metric

{"start_date"=>"2014-01-01T00:00:00Z", "end_date"=>"2014-12-31T00:00:00Z", "subject_areas"=>[{"subject_area"=>"/Biology and life sciences", "average_usage"=>[291]}, {"subject_area"=>"/Biology and life sciences/Cell biology", "average_usage"=>[286]}, {"subject_area"=>"/Biology and life sciences/Developmental biology", "average_usage"=>[285]}]}
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