In vivo tracking of human hematopoiesis reveals patterns of clonal dynamics during early and steady-state reconstitution phases
Open accessAbstract
Hematopoietic stem/progenitor cells (HSPCs) are capable of supporting the lifelong production of blood cells exerting a wide spectrum of functions. Lentiviral vector HSPC gene therapy generates a human hematopoietic system stably marked at the clonal level by vector integration sites (ISs). Using IS analysis, we longitudinally tracked >89,000 clones from 15 distinct bone marrow and peripheral blood lineages purified up to 4 years after transplant in four Wiskott-Aldrich syndrome patients treated with HSPC gene therapy. We measured at the clonal level repopulating waves, populations' sizes and dynamics, activity of distinct HSPC subtypes, contribution of various progenitor classes during the early and late post-transplant phases, and hierarchical relationships among lineages. We discovered that in-vitro-manipulated HSPCs retain the ability to return to latency after transplant and can be physiologically reactivated, sustaining a stable hematopoietic output. This study constitutes in vivo comprehensive tracking in humans of hematopoietic clonal dynamics during the early and late post-transplant phases.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Myeloid cells and adipocytes produce numerous proinflammatory cytokines leading to a vicious cycle with accumulation of myeloid or myeloid-skewed cells in the BM.
“Myeloid cells and adipocytes further produce numerous proinflammatory cytokines leading to a vicious cycle with accumulation of myeloid or myelodid-skewed cells in the BM.48”
From Inflammatory bone marrow microenvironment (2019) · cites this paper as [48]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
A clonogenic common myeloid progenitor that gives rise to all myeloid lineages
Akashi, K., Traver, D., Miyamoto, T., & Weissman, I. L. (2000) · Nature · doi:10.1038/35004599 · Cited by 2,617 · see citing works
The bone marrow niche for haematopoietic stem cells
Morrison, S. J., & Scadden, D. T. (2014) · Nature · doi:10.1038/nature12984 · Cited by 2,451 · see citing works
Identification of Clonogenic Common Lymphoid Progenitors in Mouse Bone Marrow
Kondo, M., Weissman, I. L., & Akashi, K. (1997) · Cell · doi:10.1016/s0092-8674(00)80453-5 · Cited by 2,253 · see citing works
Hematopoietic Stem Cell Gene Therapy with a Lentiviral Vector in X-Linked Adrenoleukodystrophy
Cartier, N., Hacein-Bey-Abina, S., Bartholomae, C. C., Veres, G., Schmidt, M., Kutschera, I., Vidaud, M., Abel, U., Dal-Cortivo, L., Caccavelli, L., et al. (2009) · Science · doi:10.1126/science.1171242 · Cited by 1,508 · see citing works
Self-citationGene therapy returns to centre stage
Naldini, L. (2015) · Nature · doi:10.1038/nature15818 · Cited by 1,184 · see citing works
Self-citationLentiviral Hematopoietic Stem Cell Gene Therapy Benefits Metachromatic Leukodystrophy
Biffi, A., Montini, E., Lorioli, L., Cesani, M., Fumagalli, F., Plati, T., Baldoli, C., Martino, S., Calabria, A., Canale, S., et al. (2013) · Science · doi:10.1126/science.1233158 · Cited by 1,180 · see citing works
Self-citationLentiviral Hematopoietic Stem Cell Gene Therapy in Patients with Wiskott-Aldrich Syndrome
Aiuti, A., Biasco, L., Scaramuzza, S., Ferrua, F., Cicalese, M. P., Baricordi, C., Dionisio, F., Calabria, A., Giannelli, S., Castiello, M. C., et al. (2013) · Science · doi:10.1126/science.1233151 · Cited by 1,025 · see citing works
Self-citationGene Therapy for Immunodeficiency Due to Adenosine Deaminase Deficiency
Aiuti, A., Cattaneo, F., Galimberti, S., Benninghoff, U., Cassani, B., Callegaro, L., Scaramuzza, S., Andolfi, G., Mirolo, M., Brigida, I., et al. (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0805817 · Cited by 1,003 · see citing works
Self-citationPhysiological Migration of Hematopoietic Stem and Progenitor Cells
Wright, D. E., Wagers, A. J., Gulati, A. P., Johnson, F. L., & Weissman, I. L. (2001) · Science · doi:10.1126/science.1064081 · Cited by 933 · see citing works
Isolation of Single Human Hematopoietic Stem Cells Capable of Long-Term Multilineage Engraftment
Notta, F., Doulatov, S., Laurenti, E., Poeppl, A., Jurisica, I., & Dick, J. E. (2011) · Science · doi:10.1126/science.1201219 · Cited by 919 · see citing works
Hematopoiesis: a human perspective
Doulatov, S., Notta, F., Laurenti, E., & Dick, J. E. (2012) · Cell stem cell · doi:10.1016/j.stem.2012.01.006 · Cited by 895 · see citing works
Clonal dynamics of native haematopoiesis
Sun, J., Ramos, A., Chapman, B., Johnnidis, J. B., Le, L., Ho, Y.-J., Klein, A. M., Hofmann, O., & Camargo, F. D. (2014) · Nature · doi:10.1038/nature13824 · Cited by 803 · see citing works
Efficacy of Gene Therapy for X-Linked Severe Combined Immunodeficiency
Hacein‐Bey‐Abina, S., Hauer, J., Lim, A., Pïcard, C., Wang, G. P., Berry, C. C., Martinache, C., Rieux‐Laucat, F., Latour, S., Belohradsky, B. H., et al. (2010) · New England Journal of Medicine · doi:10.1056/nejmoa1000164 · Cited by 637 · see citing works
Identification of a Hierarchy of Multipotent Hematopoietic Progenitors in Human Cord Blood
Majeti, R., Park, C. Y., & Weissman, I. L. (2007) · Cell stem cell · doi:10.1016/j.stem.2007.10.001 · Cited by 603 · see citing works
Diverse and heritable lineage imprinting of early haematopoietic progenitors
Naik, S. H., Perié, L., Swart, E., Gerlach, C., van Rooij, N., de Boer, R. J., & Schumacher, T. N. (2013) · Nature · doi:10.1038/nature12013 · Cited by 416 · see citing works
Ex vivo gene transfer and correction for cell-based therapies
Naldini, L. (2011) · Nature Reviews Genetics · doi:10.1038/nrg2985 · Cited by 386 · see citing works
Self-citationOutcomes Following Gene Therapy in Patients With Severe Wiskott-Aldrich Syndrome
Hacein‐Bey‐Abina, S., Gaspar, H. B., Blondeau, J., Caccavelli, L., Charrier, S., Buckland, K. F., Pïcard, C., Six, E. M., Himoudi, N., Gilmour, K. C., et al. (2015) · JAMA · doi:10.1001/jama.2015.3253 · Cited by 378 · see citing works
Moratto, D., Giliani, S. C., Bonfim, C., et al. (2011) · Blood · doi:10.1182/blood-2010-11-319376 · Cited by 315 · see citing works
Jenq, R. R., & van den Brink, M. R. M. (2010) · Nature reviews. Cancer · doi:10.1038/nrc2804 · Cited by 301 · see citing works
Gaspar, H. B., Cooray, S., Gilmour, K. C., Parsley, K. L., Zhang, F., Adams, S. P., Bjorkegren, E., Xu‐Bayford, J., Brown, L., Davies, E. G., et al. (2011) · Science Translational Medicine · doi:10.1126/scitranslmed.3002716 · Cited by 284 · see citing works
Cellular barcoding tool for clonal analysis in the hematopoietic system
Gerrits, A., Dykstra, B. J., Kalmykowa, O. J., Klauke, K., Verovskaya, E. V., Broekhuis, M., de Haan, G., & Bystrykh, L. V. (2010) · Blood · doi:10.1182/blood-2009-06-229757 · Cited by 253 · see citing works
Aiuti, A., Cassani, B., Andolfi, G., Mirolo, M., Biasco, L., Recchia, A., Urbinati, F., Valacca, C., Scaramuzza, S., Aker, M., et al. (2007) · Journal of Clinical Investigation · doi:10.1172/jci31666 · Cited by 252 · see citing works
Self-citationCandotti, F., Shaw, K. L., Muul, L. M., Carbonaro, D. A., Sokolic, R. A., Choi, C., Schurman, S. H., Garabedian, E., Kesserwan, C. A., Jagadeesh, G. J., et al. (2012) · Blood · doi:10.1182/blood-2012-02-400937 · Cited by 233 · see citing works
Laurenti, E., Doulatov, S. R., Zandi, S., Plumb, I., Chen, J., April, C., Fan, J., & Dick, J. E. (2013) · Nature Immunology · doi:10.1038/ni.2615 · Cited by 224 · see citing works
Intermediate-Term Hematopoietic Stem Cells with Extended but Time-Limited Reconstitution Potential
Benveniste, P. M., Frelin, C., Janmohamed, S., Barbara, M., Herrington, R., Hyam, D., & Iscove, N. N. (2010) · Cell stem cell · doi:10.1016/j.stem.2009.11.014 · Cited by 217 · see citing works
Mohty, M., Hübel, K., Kröger, N. M., et al. (2014) · Bone Marrow Transplantation · doi:10.1038/bmt.2014.39 · Cited by 197 · see citing works
Wu, C., Li, B., Lu, R., Koelle, S., Yang, Y., Jares, A., Krouse, A. E., Metzger, M. E., Liang, F., Loré, K., et al. (2014) · Cell stem cell · doi:10.1016/j.stem.2014.01.020 · Cited by 186 · see citing works
Nolta, J. A., Dao, M. A., Wells, S., et al. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.6.2414 · Cited by 182 · see citing works
Biasco, L., Scala, S., Basso Ricci, L., Dionisio, F., Baricordi, C., Calabria, A., Giannelli, S., Cieri, N., Barzaghi, F., Pajno, R., et al. (2015) · Science Translational Medicine · doi:10.1126/scitranslmed.3010314 · Cited by 175 · see citing works
Self-citationAlho, A. C., Kim, H. T., Chammas, M. J., Reynolds, C. G., Matos, T. R., Forcade, É., Whangbo, J., Nikiforow, S., Cutler, C. S., Koreth, J., et al. (2015) · Blood · doi:10.1182/blood-2015-10-672345 · Cited by 174 · see citing works
Heterogeneity and hierarchy of hematopoietic stem cells
Ema, H., Morita, Y., & Suda, T. (2013) · Experimental Hematology · doi:10.1016/j.exphem.2013.11.004 · Cited by 150 · see citing works
Natural killer–cell differentiation by myeloid progenitors
Grzywacz, B. J., Kataria, N., Kataria, N., Blazar, B. R., Miller, J. S., & Verneris, M. R. (2010) · Blood · doi:10.1182/blood-2010-04-281394 · Cited by 140 · see citing works
Wang, G. P., Berry, C., Malani, N., Leboulch, P., Fischer, A., Hacein-Bey-Abina, S., Cavazzana-Calvo, M., & Bushman, F. (2010) · Blood · doi:10.1182/blood-2009-12-257352 · Cited by 139 · see citing works
Retroviral Integrations in Gene Therapy Trials
Biasco, L., Baricordi, C., & Aiuti, A. (2012) · Molecular Therapy · doi:10.1038/mt.2011.289 · Cited by 126 · see citing works
Self-citationCheung, A. M. S., Nguyen, L. V., Carles, A., Beer, P. A., Miller, P. H., Knapp, D. J. H. F., Dhillon, K., Hirst, M., & Eaves, C. J. (2013) · Blood · doi:10.1182/blood-2013-06-508432 · Cited by 105 · see citing works
Dynamics of HSPC Repopulation in Nonhuman Primates Revealed by a Decade-Long Clonal-Tracking Study
Kim, S., Kim, N., Presson, A. P., Metzger, M. E., Bonifacino, A. C., Sehl, M. E., Chow, S. A., Crooks, G. M., Dunbar, C. E., An, D. S., et al. (2014) · Cell stem cell · doi:10.1016/j.stem.2013.12.012 · Cited by 103 · see citing works
Kawamoto, H., Ikawa, T., Masuda, K., Wada, H., & Katsura, Y. (2010) · Immunological Reviews · doi:10.1111/j.1600-065x.2010.00959.x · Cited by 89 · see citing works
Hematopoietic stem cells for cancer immunotherapy
Gschweng, E. H., Oliveira, S. N. D., & Kohn, D. B. (2013) · Immunological Reviews · doi:10.1111/imr.12128 · Cited by 89 · see citing works
Scaramuzza, S., Biasco, L., Ripamonti, A., Castiello, M. C., Loperfido, M., Draghici, E., Hernández, R. J., Benedicenti, F., Radrizzani, M., Salomoni, M., et al. (2012) · Molecular Therapy · doi:10.1038/mt.2012.23 · Cited by 86 · see citing works
Self-citationOutcomes following hematopoietic cell transplantation for Wiskott–Aldrich syndrome
Shin, C. R., Kim, M.-O., Li, D., et al. (2012) · Bone Marrow Transplantation · doi:10.1038/bmt.2012.31 · Cited by 81 · see citing works
Pai, S.-Y., DeMartiis, D., Forino, C., et al. (2006) · Bone Marrow Transplantation · doi:10.1038/sj.bmt.1705512 · Cited by 79 · see citing works
Clinical Applications of Gene Therapy for Primary Immunodeficiencies
Cicalese, M. P., & Aiuti, A. (2015) · Human Gene Therapy · doi:10.1089/hum.2015.047 · Cited by 79 · see citing works
Self-citationHierarchical organization of fetal and adult hematopoietic stem cells
Babovic, S., & Eaves, C. J. (2014) · Experimental Cell Research · doi:10.1016/j.yexcr.2014.08.005 · Cited by 75 · see citing works
Castiello, M. C., Scaramuzza, S., Pala, F., et al. (2015) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2015.01.035 · Cited by 50 · see citing works
Self-citationA revised scheme for developmental pathways of hematopoietic cells: the myeloid-based model
Kawamoto, H., Wada, H., & Katsura, Y. (2010) · International Immunology · doi:10.1093/intimm/dxp125 · Cited by 49 · see citing works
Determining Lineage Pathways from Cellular Barcoding Experiments
Perié, L., Hodgkin, P. D., Naik, S. H., Schumacher, T. N., de Boer, R. J., & Duffy, K. R. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.01.016 · Cited by 49 · see citing works
Haematopoietic stem cell transplantation for SCID patients: where do we stand?
Cavazzana, M., André‐Schmutz, I., & Fischer, A. (2012) · British Journal of Haematology · doi:10.1111/bjh.12119 · Cited by 45 · see citing works
The Continuing Contribution of Gene Marking to Cell and Gene Therapy
Tey, S., & Brenner, M. K. (2007) · Molecular Therapy · doi:10.1038/sj.mt.6300109 · Cited by 19 · see citing works
Molecular and functional characterization of early human hematopoiesis
Laurenti, E., & Dick, J. E. (2012) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2012.06577.x · Cited by 18 · see citing works
Broadening the Indications for Hematopoietic Stem Cell Genetic Therapies
Williams, D. A. (2013) · Cell stem cell · doi:10.1016/j.stem.2013.08.006 · Cited by 13 · see citing works
No Monkeying Around: Clonal Tracking of Stem Cells and Progenitors in the Macaque
Dykstra, B. J., & Bystrykh, L. V. (2014) · Cell stem cell · doi:10.1016/j.stem.2014.03.006 · Cited by 5 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Population dynamics of normal human blood inferred from somatic mutations
Lee-Six, H., Øbro, N. F., Shepherd, M. S., Grossmann, S., Dawson, K., Belmonte, M., Osborne, R. J., Huntly, B. J. P., Martincorena, I., Anderson, E., et al. (2018) · Nature · doi:10.1038/s41586-018-0497-0 · Cited by 604 · see citing works
A comprehensive single cell transcriptional landscape of human hematopoietic progenitors
Pellin, D., Loperfido, M., Baricordi, C., Wolock, S. L., Montepeloso, A., Weinberg, O. K., Biffi, A., Klein, A. M., & Biasco, L. (2019) · Nature Communications · doi:10.1038/s41467-019-10291-0 · Cited by 360 · see citing works
Self-citationHematopoietic Stem Cells Are the Major Source of Multilineage Hematopoiesis in Adult Animals
Sawai, C. M., Babovic, S., Upadhaya, S., Knapp, D. J. H. F., Lavin, Y., Lau, C. M., Goloborodko, A., Feng, J., Fujisaki, J., Ding, L., et al. (2016) · Immunity · doi:10.1016/j.immuni.2016.08.007 · Cited by 381 · see citing works
Unraveling Hematopoiesis through the Lens of Genomics
Liggett, L. A., & Sankaran, V. G. (2020) · Cell · doi:10.1016/j.cell.2020.08.030 · Cited by 163 · see citing works
Säwen, P., Eldeeb, M., Erlandsson, E., Kristiansen, T. A., Laterza, C., Kokaia, Z., Karlsson, G., Yuan, J., Soneji, S., Mandal, P. K., et al. (2018) · eLife · doi:10.7554/elife.41258 · Cited by 120 · see citing works
Inflammatory bone marrow microenvironment
Leimkühler, N. B., & Schneider, R. K. (2019) · Hematology · doi:10.1182/hematology.2019000045 · Cited by 82 · see citing works
Piras, F., Riba, M., Petrillo, C., Lazarevic, D., Cuccovillo, I., Bartolaccini, S., Stupka, E., Gentner, B., Cittaro, D., Naldini, L., et al. (2017) · EMBO Molecular Medicine · doi:10.15252/emmm.201707922 · Cited by 75 · see citing works
Self-citationThe Source and Dynamics of Adult Hematopoiesis: Insights from Lineage Tracing
Pucella, J. N., Upadhaya, S., & Reizis, B. (2020) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-020520-114601 · Cited by 53 · see citing works
Lareau, C. A., Ludwig, L. S., & Sankaran, V. G. (2019) · Blood Advances · doi:10.1182/bloodadvances.2019001196 · Cited by 17 · see citing works
- Authors
- Biasco, L., Pellin, D., Scala, S., Dionisio, F., Basso-Ricci, L., Leonardelli, L., Scaramuzza, S., Baricordi, C., Ferrua, F., Cicalese, M. P., Giannelli, S., Neduva, V., Dow, D. J., Schmidt, M., Von Kalle, C., Roncarolo, M. G., Ciceri, F., Vicard, P., Wit, E., Di Serio, C., Naldini, L., & Aiuti, A.
- Affiliations
- The San Raffaele Telethon Institute for Gene Therapy (IT)
- Vita-Salute San Raffaele University (IT)
- IRCCS Ospedale San Raffaele (IT)
- GlaxoSmithKline (United Kingdom) (GB)
- German Cancer Research Center (DE)
- Stanford Medicine (US)
- Roma Tre University (IT)
- University of Groningen (NL)
- Corresponding author
- Biasco, Luca
- Aiuti, Alessandro
- ORCID
- Venue
- Cell stem cell
- Publisher
- Elsevier BV
- Published
- 2016-07
- Volume
- 19
- Issue
- 1
- Pages
- 107-119
- ISSN
- 1875-9777 (ISSN-L)
- 1934-5909
- PMC
- PMC4942697
- OpenAlex
- W2400758624
- Cited by
- 243
- References
- 51
- Citations by year
- 2026: 11 · 2025: 13 · 2024: 23 · 2023: 27 · 2022: 26 · 2021: 24 · 2020: 34 · 2019: 23 · 2018: 24 · 2017: 27 · 2016: 10 · 2015: 1
- FWCI
- 26.65
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Cell stem cell (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Archivio istituzionale della ricerca (Alma Mater Studiorum Università di Bologna) (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Iris (Roma Tre University) (submittedVersion)
- Archivio Istituzionale della Ricerca - Università Vita-Salute San Raffaele (submittedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, cc-by-nc-nd)
- Funders
- GlaxoSmithKline
- European Commission (261387)
- Fondazione Telethon
- Ministero della Salute (RF-2009-1485896)
- Topics
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Keywords
- hematopoietic stem and progenitor cells, clonal dynamics, Wiskott-Aldrich syndrome, lentiviral gene therapy, hematopoietic recovery, lineage hierarchy, bone marrow, peripheral blood
- MeSH terms
- Child, Preschool, Clone Cells, Hematopoiesis, Hematopoietic Stem Cells, Humans, Infant, Male, Time Factors, Wiskott-Aldrich Syndrome, Genetic Therapy, Mutagenesis, Insertional, Antigens, CD34, Cell Lineage, Multipotent Stem Cells, Cell Tracking, Cell Engineering
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
