Jennifer Bordenave, Dorota Gajda, David Michonneau, Nicolas Vallet, Mathieu F Chevalier, Emmanuelle Clappier, Pierre Lemaire, Stéphanie Mathis, Marie Robin, Aliénor Xhaard, Flore Sicre de Fontbrune, Aurélien Corneau, Sophie Caillat-Zucman, Regis Peffault de Latour, Emmanuel Curis, Gerard Socie
{"title":"Deciphering bone marrow engraftment after allogeneic stem cell transplantation in humans using single cell analyses.","authors":"Jennifer Bordenave, Dorota Gajda, David Michonneau, Nicolas Vallet, Mathieu F Chevalier, Emmanuelle Clappier, Pierre Lemaire, Stéphanie Mathis, Marie Robin, Aliénor Xhaard, Flore Sicre de Fontbrune, Aurélien Corneau, Sophie Caillat-Zucman, Regis Peffault de Latour, Emmanuel Curis, Gerard Socie","doi":"10.1172/JCI180331","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Donor cell engraftment is a pre-requisite of successful allogeneic hematopoietic stem cell transplantation. Based on peripheral blood analyses it is characterized by early myeloid recovery and T- and B-cells lymphopenia. However, cellular networks associated with bone marrow engraftment of allogeneic human cells have been poorly described.</p><p><strong>Methods: </strong>Mass cytometry and CITEseq analyses were performed on bone marrow cells, three months post-transplant in patients with acute myelogenous leukemia.</p><p><strong>Results: </strong>Mass cytometry in 26 patients and 20 healthy controls disclosed profound alterations in myeloid and B-cell progenitors, with a shift towards terminal myeloid differentiation and decreased B-cell progenitors. Unsupervised analysis separated recipients into 2 groups, one of them being driven by previous GVHD (R2 patients). We then used single-cell CITEseq to decipher engraftment, which resolved 36 clusters, encompassing all bone marrow cellular components. Hematopoiesis in transplant recipients was sustained by committed myeloid and erythroid progenitors in a setting of monocytes-, NK cells- and T-cells mediated inflammation. Gene expression disclosed major pathways in transplant recipients, namely, TNFα signaling via NFκ-B, and interferon-γ response. The hallmark of allograft rejection was consistently found in clusters from transplant recipients, especially in R2 recipients.</p><p><strong>Conclusion: </strong>Bone marrow cell engraftment of allogeneic donor cells is characterized by a state of emergency hematopoiesis in the setting of allogeneic response driving inflammation.</p><p><strong>Trial registration: </strong>Not applicable.</p><p><strong>Funding: </strong>This study has been supported by the French National Cancer Institute (Institut National du Cancer): PLBIO19-239 and by an unrestricted research grant by Alexion Pharmaceutical.</p>","PeriodicalId":15469,"journal":{"name":"Journal of Clinical Investigation","volume":null,"pages":null},"PeriodicalIF":13.3000,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Clinical Investigation","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1172/JCI180331","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
引用次数: 0
Abstract
Background: Donor cell engraftment is a pre-requisite of successful allogeneic hematopoietic stem cell transplantation. Based on peripheral blood analyses it is characterized by early myeloid recovery and T- and B-cells lymphopenia. However, cellular networks associated with bone marrow engraftment of allogeneic human cells have been poorly described.
Methods: Mass cytometry and CITEseq analyses were performed on bone marrow cells, three months post-transplant in patients with acute myelogenous leukemia.
Results: Mass cytometry in 26 patients and 20 healthy controls disclosed profound alterations in myeloid and B-cell progenitors, with a shift towards terminal myeloid differentiation and decreased B-cell progenitors. Unsupervised analysis separated recipients into 2 groups, one of them being driven by previous GVHD (R2 patients). We then used single-cell CITEseq to decipher engraftment, which resolved 36 clusters, encompassing all bone marrow cellular components. Hematopoiesis in transplant recipients was sustained by committed myeloid and erythroid progenitors in a setting of monocytes-, NK cells- and T-cells mediated inflammation. Gene expression disclosed major pathways in transplant recipients, namely, TNFα signaling via NFκ-B, and interferon-γ response. The hallmark of allograft rejection was consistently found in clusters from transplant recipients, especially in R2 recipients.
Conclusion: Bone marrow cell engraftment of allogeneic donor cells is characterized by a state of emergency hematopoiesis in the setting of allogeneic response driving inflammation.
Trial registration: Not applicable.
Funding: This study has been supported by the French National Cancer Institute (Institut National du Cancer): PLBIO19-239 and by an unrestricted research grant by Alexion Pharmaceutical.
期刊介绍:
The Journal of Clinical Investigation, established in 1924 by the ASCI, is a prestigious publication that focuses on breakthroughs in basic and clinical biomedical science, with the goal of advancing the field of medicine. With an impressive Impact Factor of 15.9 in 2022, it is recognized as one of the leading journals in the "Medicine, Research & Experimental" category of the Web of Science.
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The Editorial Board consists of esteemed academic editors who possess extensive expertise in their respective fields. They are actively involved in research, ensuring the journal's high standards of publication and scientific rigor.