Advances in complex multiparameter flow cytometry technology: Applications in stem cell research

Flow cytometry and cell sorting are critical tools in stem cell research. Recent advances in flow cytometric hardware, reagents, and software have synergized to permit the stem cell biologist to more fully identify and isolate rare cells based on their immunofluorescent and light scatter characteristics. Some of these improvements include physically smaller air‐cooled lasers, new designs in optics, new fluorescent conjugate‐excitation pairs, and improved software to visualize data, all which combine to open up new horizons in the study of stem cells, by enhancing the resolution and specificity of inquiry. In this review, these recent improvements in technology will be outlined and important cell surface and functional antigenic markers useful for the study of stem cells described. © 2009 Clinical Cytometry Society

[1]  M. Roederer,et al.  Optimizing a multicolor immunophenotyping assay. , 2007, Clinics in laboratory medicine.

[2]  Garry P. Nolan,et al.  Simultaneous measurement of multiple active kinase states using polychromatic flow cytometry , 2002, Nature Biotechnology.

[3]  S. Jacobsen,et al.  Upregulation of Flt3 expression within the bone marrow Lin(-)Sca1(+)c-kit(+) stem cell compartment is accompanied by loss of self-renewal capacity. , 2001, Immunity.

[4]  Mario Roederer,et al.  Dear Reader, , 2003, Nature Medicine.

[5]  Keisuke Ito,et al.  Tie2/Angiopoietin-1 Signaling Regulates Hematopoietic Stem Cell Quiescence in the Bone Marrow Niche , 2004, Cell.

[6]  E. Podniesinski,et al.  Flow cytometer in the infrared: Inexpensive modifications to a commercial instrument , 2005, Cytometry. Part A : the journal of the International Society for Analytical Cytology.

[7]  L. Kunkel,et al.  Skeletal muscle engraftment potential of adult mouse skin side population cells , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[8]  R. Schofield.  The relationship between the spleen colony-forming cell and the haemopoietic stem cell. , 1978, Blood cells.

[9]  M. Pittenger,et al.  Human mesenchymal stem cells modulate allogeneic immune cell responses. , 2005, Blood.

[10]  D. Krause,et al.  Limitations of Green Fluorescent Protein as a Cell Lineage Marker , 2007, Stem cells.

[11]  A. Ullrich,et al.  Expression of c-kit receptor in normal and transformed human nonlymphoid tissues. , 1992, Cancer research.

[12]  S. E. Jacobsen,et al.  Identification of Lin(-)Sca1(+)kit(+)CD34(+)Flt3- short-term hematopoietic stem cells capable of rapidly reconstituting and rescuing myeloablated transplant recipients. , 2005, Blood.

[13]  H. Nakauchi,et al.  The ABC transporter Bcrp1/ABCG2 is expressed in a wide variety of stem cells and is a molecular determinant of the side-population phenotype , 2001, Nature Medicine.

[14]  M. Fulwyler,et al.  Electronic Separation of Biological Cells by Volume , 1965, Science.

[15]  M. Maio,et al.  Highlights on endoglin (CD105): from basic findings towards clinical applications in human cancer , 2004, Journal of Translational Medicine.

[16]  Y. Matsuzaki,et al.  Hematopoietic and nonhematopoietic potentials of Hoechst(low)/side population cells isolated from adult rat kidney. , 2004, Kidney international.

[17]  Leonore A Herzenberg,et al.  Interpreting flow cytometry data: a guide for the perplexed , 2006, Nature Immunology.

[18]  M. Little,et al.  A Side Order of Stem Cells: The SP Phenotype , 2006, Stem cells.

[19]  M. Mattson,et al.  Membrane properties of rat embryonic multipotent neural stem cells , 2003, Journal of neurochemistry.

[20]  H. Okano,et al.  Unexpectedly efficient homing capacity of purified murine hematopoietic stem cells. , 2004, Immunity.

[21]  J. Dick,et al.  Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell , 1997, Nature Medicine.

[22]  P. Lansdorp,et al.  Characterization and partial purification of human marrow cells capable of initiating long-term hematopoiesis in vitro. , 1989, Blood.

[23]  M. Andreeff,et al.  A leukemic stem cell with intrinsic drug efflux capacity in acute myeloid leukemia. , 2001, Blood.

[24]  S. Salani,et al.  Identification of a Primitive Brain–Derived Neural Stem Cell Population Based on Aldehyde Dehydrogenase Activity , 2006, Stem cells.

[25]  B. Wood,et al.  9-color and 10-color flow cytometry in the clinical laboratory. , 2006, Archives of pathology & laboratory medicine.

[26]  F. Lanza,et al.  Structural and functional features of the CD34 antigen: an update. , 2001, Journal of biological regulators and homeostatic agents.

[27]  V. Sharma,et al.  HLA-mismatched renal transplantation without maintenance immunosuppression. , 2008, The New England journal of medicine.

[28]  R. Mulligan,et al.  Dystrophin expression in the mdx mouse restored by stem cell transplantation , 1999, Nature.

[29]  H. Deeg,et al.  Ultrastructural localization of stem cell factor in canine marrow-derived stromal cells. , 1995, Experimental hematology.

[30]  J. Dick,et al.  Cancer stem cells: lessons from leukemia. , 2005, Trends in cell biology.

[31]  B. Hallberg,et al.  c-Kit--a hematopoietic cell essential receptor tyrosine kinase. , 2007, The international journal of biochemistry & cell biology.

[32]  M. Fackler,et al.  Characterization of murine CD34, a marker for hematopoietic progenitor and stem cells. , 1994, Blood.

[33]  M. Fukuda,et al.  [Studies on the haematopoietic stem cells in primary myelofibrosis--in vitro colony forming capacity of the peripheral blood, the spleen, the splenic arterial and venous blood (author's transl)]. , 1978, [Rinsho ketsueki] The Japanese journal of clinical hematology.

[34]  R A Hoffman,et al.  Evaluating fluorescence sensitivity on flow cytometers: an overview. , 1998, Cytometry.

[35]  J. Müller,et al.  Detection of cytogenetic aberrations both in CD90 (Thy-1)-positive and (Thy-1)-negative stem cell (CD34) subfractions of patients with acute and chronic myeloid leukemias , 1999, Leukemia.

[36]  N. Wolf,et al.  In vivo and in vitro characterization of long-term repopulating primitive hematopoietic cells isolated by sequential Hoechst 33342-rhodamine 123 FACS selection. , 1993, Experimental hematology.

[37]  D. Bonnet,et al.  The combined use of Hoechst efflux ability and aldehyde dehydrogenase activity to identify murine and human hematopoietic stem cells. , 2007, Experimental hematology.

[38]  M Roederer,et al.  Probability binning comparison: a metric for quantitating multivariate distribution differences. , 2001, Cytometry.

[39]  Tymish Y. Ohulchanskyy,et al.  High contrast in vitro and in vivo photoluminescence bioimaging using near infrared to near infrared up-conversion in Tm3+ and Yb3+ doped fluoride nanophosphors. , 2008, Nano letters.

[40]  C. Heyworth,et al.  AC133+ G0 Cells from Cord Blood Show a High Incidence of Long‐Term Culture–Initiating Cells and a Capacity for More Than 100 Million‐Fold Amplification of Colony‐Forming Cells In Vitro , 2004, Stem cells.

[41]  F. Gonzalez-fernandez,et al.  Cancer stem cell characteristics in retinoblastoma. , 2005, Molecular vision.

[42]  G. van den Engh,et al.  Kinetic analyses as a critical parameter in defining the side population (SP) phenotype. , 2007, Experimental cell research.

[43]  N. Voelkel,et al.  Identification of Novel Resident Pulmonary Stem Cells: Form and Function of the Lung Side Population , 2005, Stem cells.

[44]  T. Kondo,et al.  Persistence of a small subpopulation of cancer stem-like cells in the C6 glioma cell line. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[45]  G. Bernardi,et al.  Identification and enrichment of spermatogonial stem cells displaying side‐population phenotype in immature mouse testis , 2004, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[46]  R. Johnson,et al.  Dye efflux studies suggest that hematopoietic stem cells expressing low or undetectable levels of CD34 antigen exist in multiple species , 1997, Nature Medicine.

[47]  H. Broxmeyer,et al.  Hematopoietic defects in mice lacking the sialomucin CD34. , 1996, Blood.

[48]  Nathan C Boles,et al.  CD150- side population cells represent a functionally distinct population of long-term hematopoietic stem cells. , 2008, Blood.

[49]  L. Kanz,et al.  Effect of FLT3 Inhibition on Normal Hematopoietic Progenitor Cells , 2007, Annals of the New York Academy of Sciences.

[50]  D. Niedzwiecki,et al.  Distinct hematopoietic progenitor compartments are delineated by the expression of aldehyde dehydrogenase and CD34. , 2005, Blood.

[51]  P. Donahoe,et al.  Adult Mouse Myometrial Label‐Retaining Cells Divide in Response to Gonadotropin Stimulation , 2007, Stem cells.

[52]  W. Bonner,et al.  Cell Sorting: Automated Separation of Mammalian Cells as a Function of Intracellular Fluorescence , 1969, Science.

[53]  I. Weissman,et al.  Flk-2 is a marker in hematopoietic stem cell differentiation: A simple method to isolate long-term stem cells , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[54]  K. Bunting.  ABC Transporters as Phenotypic Markers and Functional Regulators of Stem Cells , 2002, Stem cells.

[55]  M. Ratajczak,et al.  “Small stem cells” in adult tissues: Very small embryonic‐like stem cells stand up! , 2009, Cytometry. Part A : the journal of the International Society for Analytical Cytology.

[56]  T. Hayakawa,et al.  CD31 (PECAM‐1)‐bright cells derived from AC133‐positive cells in human peripheral blood as endothelial‐precursor cells , 2003, Journal of cellular physiology.

[57]  T. Brümmendorf,et al.  CDCP1 Identifies a Broad Spectrum of Normal and Malignant Stem/Progenitor Cell Subsets of Hematopoietic and Nonhematopoietic Origin , 2004, Stem cells.

[58]  Laurie Lamoreaux,et al.  Amine reactive dyes: an effective tool to discriminate live and dead cells in polychromatic flow cytometry. , 2006, Journal of immunological methods.

[59]  R. Colvin,et al.  Analysis and Sorting by Flow Cytometry: Applications to the Study of Human Disease , 1987 .

[60]  C. Dive,et al.  Flow Cytometry and Sorting , 1991, British Journal of Cancer.

[61]  Matthew D. Cooper,et al.  Revealing Structure in Visualizations of Dense 2D and 3D Parallel Coordinates , 2006, Inf. Vis..

[62]  R. Handgretinger,et al.  Selection of Stem Cells by Using Antibodies That Target Different CD34 Epitopes Yields Different Patterns of T‐Cell Differentiation , 2007, Stem cells.

[63]  M. Goodell,et al.  Cells of the hepatic side population contribute to liver regeneration and can be replenished with bone marrow stem cells. , 2003, Haematologica.

[64]  Edward J. Wegman,et al.  High Dimensional Clustering Using Parallel Coordinates and the Grand Tour , 1997 .

[65]  L. Kamentsky,et al.  Spectrophotometer: New Instrument for Ultrarapid Cell Analysis , 1965, Science.

[66]  D. Scadden,et al.  Lineage‐Negative Side‐Population (SP) Cells with Restricted Hematopoietic Capacity Circulate in Normal Human Adult Blood: Immunophenotypic and Functional Characterization , 2002, Stem cells.

[67]  Nathan C Boles,et al.  Mouse hematopoietic stem cell identification and analysis , 2009, Cytometry. Part A : the journal of the International Society for Analytical Cytology.

[68]  R. Mulligan,et al.  Use of CD9 expression to enrich for porcine hematopoietic progenitors. , 2002, Experimental hematology.

[69]  Daniel Haley,et al.  Polychromatic flow cytometry: A rapid method for the reduction and analysis of complex multiparameter data , 2006, Cytometry. Part A : the journal of the International Society for Analytical Cytology.

[70]  C Bruce Bagwell,et al.  Breaking the dimensionality barrier. , 2011, Methods in molecular biology.

[71]  J. Till,et al.  A direct measurement of the radiation sensitivity of normal mouse bone marrow cells. , 1961, Radiation research.

[72]  T. Nakano,et al.  In Vitro Proliferation Potential of AC133 Positive Cells in Peripheral Blood , 2000, Stem cells.

[73]  G. Vereb,et al.  Die hard: Are cancer stem cells the Bruce Willises of tumor biology? , 2009, Cytometry. Part A : the journal of the International Society for Analytical Cytology.

[74]  C. Esmon,et al.  Endothelial protein C receptor (CD201) explicitly identifies hematopoietic stem cells in murine bone marrow. , 2006, Blood.

[75]  E. Lander,et al.  Identification of endoglin as a functional marker that defines long-term repopulating hematopoietic stem cells , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[76]  Xiaojie Li,et al.  Rapid and selective death of leukemia stem and progenitor cells induced by the compound 4-benzyl, 2-methyl, 1,2,4-thiadiazolidine, 3,5 dione (TDZD-8). , 2007, Blood.

[77]  S. Morrison,et al.  Supplemental Experimental Procedures , 2022 .

[78]  R. Gilbertson,et al.  Tumorigenesis in the brain: location, location, location. , 2007, Cancer research.

[79]  M. Ratajczak,et al.  Hunt for pluripotent stem cell -- regenerative medicine search for almighty cell. , 2008, Journal of autoimmunity.

[80]  V. Dill,et al.  Flow cytometry : instrumentation and data analysis , 1987 .

[81]  Aleksandar Dakic,et al.  Tumor Growth Need Not Be Driven by Rare Cancer Stem Cells , 2007, Science.

[82]  D. Sutherland,et al.  Re: Selection of Stem Cells by Using Antibodies That Target Different CD34 Epitopes Yields Different Patterns of T‐Cell Differentiation , 2007, Stem cells.

[83]  M. Goodell,et al.  Purification of hematopoietic stem cells using the side population. , 2006, Methods in enzymology.

[84]  N. Clarke,et al.  Characterization of benign and malignant prostate epithelial Hoechst 33342 side populations , 2007, The Prostate.

[85]  M. Chalfie,et al.  Green fluorescent protein as a marker for gene expression. , 1994, Science.

[86]  A. Ullrich,et al.  Human proto‐oncogene c‐kit: a new cell surface receptor tyrosine kinase for an unidentified ligand. , 1987, The EMBO journal.

[87]  Mario Roederer,et al.  A new “Logicle” display method avoids deceptive effects of logarithmic scaling for low signals and compensated data , 2006, Cytometry. Part A : the journal of the International Society for Analytical Cytology.

[88]  R. Moon,et al.  Wnt signaling promotes hematoendothelial cell development from human embryonic stem cells. , 2008, Blood.

[89]  S C De Rosa,et al.  Eleven-color flow cytometry. A powerful tool for elucidation of the complex immune system. , 2001, Clinics in laboratory medicine.

[90]  Peter T Masiakos,et al.  Ovarian cancer side population defines cells with stem cell-like characteristics and Mullerian Inhibiting Substance responsiveness. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[91]  Jonathan M Irish,et al.  Analysis of protein phosphorylation and cellular signaling events by flow cytometry: techniques and clinical applications. , 2004, Clinical immunology.

[92]  D. Metcalfe,et al.  The protooncogene c-kit and c-kit ligand in human disease. , 1997, The Journal of allergy and clinical immunology.

[93]  Horst Bischof,et al.  3D parallel coordinate systems—A new data visualization method in the context of microscopy‐based multicolor tissue cytometry , 2006, Cytometry. Part A : the journal of the International Society for Analytical Cytology.

[94]  J. Goldman,et al.  4-Hydroperoxycyclophosphamide inhibits proliferation by human granulocyte-macrophage colony-forming cells (GM-CFC) but spares more primitive progenitor cells. , 1985, Leukemia research.

[95]  Erkki Ruoslahti,et al.  Nanocrystal targeting in vivo , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[96]  Graham Dellaire,et al.  Application of Quantum Dots as Probes for Correlative Fluorescence, Conventional, and Energy-filtered Transmission Electron Microscopy , 2004, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[97]  G. van den Engh,et al.  Chromatic shifts in the fluorescence emitted by murine thymocytes stained with Hoechst 33342 , 2004, Cytometry. Part A : the journal of the International Society for Analytical Cytology.

[98]  C. Kuperwasser,et al.  Human breast cancer stem cell markers CD44 and CD24: enriching for cells with functional properties in mice or in man? , 2007, Breast Cancer Research.

[99]  W. Telford,et al.  The Minimal Instrumentation Requirements for Hoechst Side Population Analysis: Stem Cell Analysis on Low‐Cost Flow Cytometry Platforms , 2006, Stem cells.

[100]  M. Roederer,et al.  Probability binning comparison: a metric for quantitating univariate distribution differences. , 2001, Cytometry.

[101]  James F Leary,et al.  Ultra high‐speed sorting , 2005, Cytometry. Part A : the journal of the International Society for Analytical Cytology.

[102]  Wade T Rogers,et al.  Cytometric fingerprinting: Quantitative characterization of multivariate distributions , 2008, Cytometry. Part A : the journal of the International Society for Analytical Cytology.

[103]  Haiyang Huang,et al.  Identification of the haematopoietic stem cell niche and control of the niche size , 2003, Nature.

[104]  S. Bapat,et al.  CD133‐Expressing Stem Cells Associated with Ovarian Metastases Establish an Endothelial Hierarchy and Contribute to Tumor Vasculature , 2009, Stem cells.

[105]  J C Wood,et al.  Fundamental flow cytometer properties governing sensitivity and resolution. , 1998, Cytometry.

[106]  S. Haeryfar,et al.  Thy-1: More than a Mouse Pan-T Cell Marker1 , 2004, The Journal of Immunology.

[107]  I. Weissman,et al.  Two rare populations of mouse Thy-1lo bone marrow cells repopulate the thymus , 1988, The Journal of experimental medicine.

[108]  R. V. van Etten,et al.  Right on target: eradicating leukemic stem cells. , 2007, Trends in molecular medicine.

[109]  J. Nolta,et al.  Selection based on CD133 and high aldehyde dehydrogenase activity isolates long-term reconstituting human hematopoietic stem cells. , 2006, Blood.

[110]  S. Morrison,et al.  Prospective identification of tumorigenic breast cancer cells , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[111]  S. Rafii,et al.  AC133/CD133/Prominin-1. , 2005, The international journal of biochemistry & cell biology.

[112]  I. Weissman,et al.  Isolation of two early B lymphocyte progenitors from mouse marrow: A committed Pre-Pre-B cell and a clonogenic Thy-1lo hematopoietic stem cell , 1986, Cell.

[113]  Steven W Graves,et al.  Ultrasonic particle‐concentration for sheathless focusing of particles for analysis in a flow cytometer , 2006, Cytometry. Part A : the journal of the International Society for Analytical Cytology.

[114]  John Ferbas,et al.  Mixture modeling approach to flow cytometry data , 2008, Cytometry. Part A : the journal of the International Society for Analytical Cytology.

[115]  D. Scadden,et al.  Osteoblastic cells regulate the haematopoietic stem cell niche , 2003, Nature.

[116]  N. Bresolin,et al.  Human skin‐derived stem cells migrate throughout forebrain and differentiate into astrocytes after injection into adult mouse brain , 2004, Journal of neuroscience research.

[117]  Z. Diwu,et al.  3-Carboxy-6-chloro-7-hydroxycoumarin: a highly fluorescent, water-soluble violet-excitable dye for cell analysis. , 2009, Analytical biochemistry.

[118]  H. Shapiro.  Practical Flow Cytometry: Shapiro/Flow Cytometry 4e , 2005 .

[119]  Vladislav V Verkhusha,et al.  New lasers for flow cytometry: filling the gaps , 2007, Nature Methods.

[120]  O. Ringdén,et al.  Immunobiology of human mesenchymal stem cells and future use in hematopoietic stem cell transplantation. , 2005, Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation.

[121]  R. Warnke,et al.  A novel five-transmembrane hematopoietic stem cell antigen: isolation, characterization, and molecular cloning. , 1997, Blood.

[122]  R. Parks,et al.  Hepatic progenitor cells in human fetal liver express the oval cell marker Thy-1. , 2006, American journal of physiology. Gastrointestinal and liver physiology.

[123]  Cynthia Hawkins,et al.  Identification of a cancer stem cell in human brain tumors. , 2003, Cancer research.

[124]  D. Grasso,et al.  Flow cytometry. , 1998, Methods in molecular medicine.

[125]  Lesley J. Murray,et al.  CD109 is expressed on a subpopulation of CD34+ cells enriched in hematopoietic stem and progenitor cells. , 1999, Experimental hematology.

[126]  Bernhard Ø Palsson,et al.  High‐throughput laser‐mediated in situ cell purification with high purity and yield , 2004, Cytometry. Part A : the journal of the International Society for Analytical Cytology.

[127]  Richard J. Jones,et al.  Assessment of aldehyde dehydrogenase in viable cells. , 1995, Blood.

[128]  A. Keating,et al.  Differential sensitivity of CD34 epitopes to cleavage by Pasteurella haemolytica glycoprotease: implications for purification of CD34-positive progenitor cells. , 1992, Experimental hematology.

[129]  Daniela S Krause,et al.  Tyrosine kinases as targets for cancer therapy. , 2005, The New England journal of medicine.

[130]  Mehmet Toner,et al.  Blood-on-a-chip. , 2005, Annual review of biomedical engineering.

[131]  A. S. Conner,et al.  Isolation and functional properties of murine hematopoietic stem cells that are replicating in vivo , 1996, The Journal of experimental medicine.

[132]  T. Graubert,et al.  Sca-1(pos) cells in the mouse mammary gland represent an enriched progenitor cell population. , 2002, Developmental biology.

[133]  J. Nolta,et al.  Functional characterization of highly purified human hematopoietic repopulating cells isolated according to aldehyde dehydrogenase activity. , 2004, Blood.

[134]  B. Lord,et al.  CD34+AC133+ Cells Isolated from Cord Blood are Highly Enriched in Long‐Term Culture‐Initiating Cells, NOD/SCID‐Repopulating Cells and Dendritic Cell Progenitors , 1998, Stem cells.

[135]  D. Stroncek,et al.  CD177: A member of the Ly-6 gene superfamily involved with neutrophil proliferation and polycythemia vera , 2004, Journal of Translational Medicine.

[136]  W. Telford,et al.  Supercontinuum white light lasers for flow cytometry , 2009, Cytometry. Part A : the journal of the International Society for Analytical Cytology.

[137]  S. Morrison,et al.  SLAM family markers are conserved among hematopoietic stem cells from old and reconstituted mice and markedly increase their purity. , 2006, Blood.

[138]  A. Páldi,et al.  Combination of quantification and observation methods for study of “Side Population” cells in their “in vitro” microenvironment , 2007, Cytometry. Part A : the journal of the International Society for Analytical Cytology.

[139]  M. Roederer,et al.  A practical approach to multicolor flow cytometry for immunophenotyping. , 2000, Journal of immunological methods.

[140]  R. Murphy.  Automated identification of subpopulations in flow cytometric list mode data using cluster analysis. , 1985, Cytometry.

[141]  P. F. Mullaney,et al.  Cell Microfluorometry: A Method for Rapid Fluorescence Measurement , 1969, Science.

[142]  Raviv Raich,et al.  Analysis of clinical flow cytometric immunophenotyping data by clustering on statistical manifolds: Treating flow cytometry data as high‐dimensional objects , 2009, Cytometry. Part B, Clinical cytometry.

[143]  T. Jovin,et al.  Analysis and sorting of living cells according to deoxyribonucleic acid content. , 1977, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[144]  O. C. Blair,et al.  Practical Flow Cytometry , 1985, The Yale Journal of Biology and Medicine.

[145]  I. Weissman,et al.  Translating stem and progenitor cell biology to the clinic: barriers and opportunities. , 2000, Science.

[146]  原口 直紹.  Characterization of a side population of cancer cells from human gastrointestinal system , 2006 .

[147]  S. Salani,et al.  Transplanted ALDHhiSSClo neural stem cells generate motor neurons and delay disease progression of nmd mice, an animal model of SMARD1. , 2006, Human molecular genetics.

[148]  I. Weissman,et al.  Identification of a hierarchy of multipotent hematopoietic progenitors in human cord blood. , 2007, Cell stem cell.

[149]  K. Brennand,et al.  Normal ovarian surface epithelial label-retaining cells exhibit stem/progenitor cell characteristics , 2008, Proceedings of the National Academy of Sciences.