Deciphering bone marrow engraftment after allogeneic stem cell transplantation in humans using single-cell analyses.

Autor: Bordenave J; INSERM UMR 976, Université Paris Cité, Paris, France., Gajda D; UR 7537 BioSTM, Faculté de Pharmacie, Université Paris Cité, Paris, France., Michonneau D; INSERM UMR 976, Université Paris Cité, Paris, France.; Assistance Publique-Hôpitaux de Paris (APHP), Hématologie Greffe, Hôpital Saint Louis, Paris, France.; UFR de Médecine, Université Paris Cité, Paris, France., Vallet N; INSERM UMR 976, Université Paris Cité, Paris, France., Chevalier M; INSERM UMR 976, Université Paris Cité, Paris, France., Clappier E; UFR de Médecine, Université Paris Cité, Paris, France.; APHP, Laboratoire d'Hématologie, Hôpital Saint Louis, Saint-Louis, France., Lemaire P; APHP, Laboratoire d'Hématologie, Hôpital Saint Louis, Saint-Louis, France., Mathis S; APHP, Laboratoire d'Hématologie, Hôpital Saint Louis, Saint-Louis, France., Robin M; Assistance Publique-Hôpitaux de Paris (APHP), Hématologie Greffe, Hôpital Saint Louis, Paris, France., Xhaard A; Assistance Publique-Hôpitaux de Paris (APHP), Hématologie Greffe, Hôpital Saint Louis, Paris, France., Sicre de Fontbrune F; Assistance Publique-Hôpitaux de Paris (APHP), Hématologie Greffe, Hôpital Saint Louis, Paris, France., Corneau A; Plateforme de Cytométrie de la Pitié-Salpétrière (CyPS), UMS037-PASS, Paris, France.; Faculté de Médecine, Sorbonne Université, Paris, France., Caillat-Zucman S; INSERM UMR 976, Université Paris Cité, Paris, France.; UFR de Médecine, Université Paris Cité, Paris, France.; APHP, Laboratoire d'Immunologie, Hôpital Saint Louis, Saint-Louis, France., Peffault de Latour R; INSERM UMR 976, Université Paris Cité, Paris, France.; Assistance Publique-Hôpitaux de Paris (APHP), Hématologie Greffe, Hôpital Saint Louis, Paris, France.; UFR de Médecine, Université Paris Cité, Paris, France., Curis E; UR 7537 BioSTM, Faculté de Pharmacie, Université Paris Cité, Paris, France.; APHP, Laboratoire d'Hématologie, Hôpital Lariboisière, Paris, France., Socié G; INSERM UMR 976, Université Paris Cité, Paris, France.; Assistance Publique-Hôpitaux de Paris (APHP), Hématologie Greffe, Hôpital Saint Louis, Paris, France.; UFR de Médecine, Université Paris Cité, Paris, France.
Jazyk: angličtina
Zdroj: The Journal of clinical investigation [J Clin Invest] 2024 Aug 29; Vol. 134 (20). Date of Electronic Publication: 2024 Aug 29.
DOI: 10.1172/JCI180331
Abstrakt: BACKGROUNDDonor cell engraftment is a prerequisite of successful allogeneic hematopoietic stem cell transplantation. Based on peripheral blood analyses, it is characterized by early myeloid recovery and T and B cell lymphopenia. However, cellular networks associated with bone marrow engraftment of allogeneic human cells have been poorly described.METHODSMass cytometry and CITE-Seq analyses were performed on bone marrow cells 3 months after transplantation in patients with acute myelogenous leukemia.RESULTSMass cytometric analyses in 26 patients and 20 healthy controls disclosed profound alterations in myeloid and B cell progenitors, with a shift toward terminal myeloid differentiation and decreased B cell progenitors. Unsupervised analysis separated recipients into 2 groups, one of them being driven by previous graft-versus-host disease (R2 patients). We then used single-cell CITE-Seq 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 monocyte-, NK cell-, and T cell-mediated inflammation. Gene expression revealed major pathways in transplant recipients, namely, TNF-α signaling via NF-κB and the IFN-γ response. The hallmark of allograft rejection was consistently found in clusters from transplant recipients, especially in R2 recipients.CONCLUSIONBone marrow cell engraftment of allogeneic donor cells is characterized by a state of emergency hematopoiesis in the setting of an allogeneic response driving inflammation.FUNDINGThis study was supported by the French National Cancer Institute (Institut National du Cancer; PLBIO19-239) and by an unrestricted research grant by Alexion Pharmaceuticals.
Databáze: MEDLINE
Externí odkaz: