PMID- 37355988
OWN - NLM
STAT- MEDLINE
DCOM- 20230731
LR  - 20240121
IS  - 2211-1247 (Electronic)
VI  - 42
IP  - 7
DP  - 2023 Jul 25
TI  - Understanding heterogeneity of human bone marrow plasma cell maturation and 
      survival pathways by single-cell analyses.
PG  - 112682
LID - S2211-1247(23)00693-9 [pii]
LID - 10.1016/j.celrep.2023.112682 [doi]
LID - 112682
AB  - Human bone marrow (BM) plasma cells are heterogeneous, ranging from newly arrived 
      antibody-secreting cells (ASCs) to long-lived plasma cells (LLPCs). We provide 
      single-cell transcriptional resolution of 17,347 BM ASCs from five healthy 
      adults. Fifteen clusters are identified ranging from newly minted ASCs (cluster 
      1) expressing MKI67 and high major histocompatibility complex (MHC) class II that 
      progress to late clusters 5-8 through intermediate clusters 2-4. Additional ASC 
      clusters include the following: immunoglobulin (Ig) M predominant (likely of 
      extra-follicular origin), interferon responsive, and high mitochondrial activity. 
      Late ASCs are distinguished by G2M checkpoints, mammalian target of rapamycin 
      (mTOR) signaling, distinct metabolic pathways, CD38 expression, utilization of 
      tumor necrosis factor (TNF)-receptor superfamily members, and two distinct 
      maturation pathways involving TNF signaling through nuclear factor kappaB (NF-kappaB). 
      This study provides a single-cell atlas and molecular roadmap of LLPC maturation 
      trajectories essential in the BM microniche. Altogether, understanding BM ASC 
      heterogeneity in health and disease enables development of new strategies to 
      enhance protective ASCs and to deplete pathogenic ones.
CI  - Copyright (c) 2023 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Duan, Meixue
AU  - Duan M
AD  - School of Biological Sciences, Georgia Institute of Technology, Atlanta, GA, USA.
FAU - Nguyen, Doan C
AU  - Nguyen DC
AD  - Department of Medicine, Division of Pulmonary, Allergy, Critical Care, and Sleep 
      Medicine, Emory University, Atlanta, GA, USA.
FAU - Joyner, Chester J
AU  - Joyner CJ
AD  - Department of Medicine, Division of Pulmonary, Allergy, Critical Care, and Sleep 
      Medicine, Emory University, Atlanta, GA, USA.
FAU - Saney, Celia L
AU  - Saney CL
AD  - Department of Medicine, Division of Pulmonary, Allergy, Critical Care, and Sleep 
      Medicine, Emory University, Atlanta, GA, USA.
FAU - Tipton, Christopher M
AU  - Tipton CM
AD  - Department of Medicine, Division of Pulmonary, Allergy, Critical Care, and Sleep 
      Medicine, Emory University, Atlanta, GA, USA; Department of Medicine, Division of 
      Rheumatology, Lowance Center for Human Immunology, Emory University, Atlanta, GA, 
      USA.
FAU - Andrews, Joel
AU  - Andrews J
AD  - Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory 
      University, Atlanta, GA, USA.
FAU - Lonial, Sagar
AU  - Lonial S
AD  - Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory 
      University, Atlanta, GA, USA.
FAU - Kim, Caroline
AU  - Kim C
AD  - Department of Medicine, Division of Pulmonary, Allergy, Critical Care, and Sleep 
      Medicine, Emory University, Atlanta, GA, USA.
FAU - Hentenaar, Ian
AU  - Hentenaar I
AD  - Department of Medicine, Division of Pulmonary, Allergy, Critical Care, and Sleep 
      Medicine, Emory University, Atlanta, GA, USA.
FAU - Kosters, Astrid
AU  - Kosters A
AD  - Department of Medicine, Division of Rheumatology, Lowance Center for Human 
      Immunology, Emory University, Atlanta, GA, USA.
FAU - Ghosn, Eliver
AU  - Ghosn E
AD  - Department of Medicine, Division of Rheumatology, Lowance Center for Human 
      Immunology, Emory University, Atlanta, GA, USA.
FAU - Jackson, Annette
AU  - Jackson A
AD  - Departments of Immunology, Duke University, Durham, NC, USA; Department of 
      Surgery, Duke University, Durham, NC, USA.
FAU - Knechtle, Stuart
AU  - Knechtle S
AD  - Department of Surgery, Duke University, Durham, NC, USA.
FAU - Maruthamuthu, Stalinraja
AU  - Maruthamuthu S
AD  - Immunogenetics and Transplantation Laboratory, Department of Surgery, University 
      of California San Francisco, San Francisco, CA, USA.
FAU - Chandran, Sindhu
AU  - Chandran S
AD  - Department of Medicine, University of California San Francisco, San Francisco, 
      CA, USA.
FAU - Martin, Tom
AU  - Martin T
AD  - Department of Medicine, University of California San Francisco, San Francisco, 
      CA, USA.
FAU - Rajalingam, Raja
AU  - Rajalingam R
AD  - Immunogenetics and Transplantation Laboratory, Department of Surgery, University 
      of California San Francisco, San Francisco, CA, USA.
FAU - Vincenti, Flavio
AU  - Vincenti F
AD  - Division of Nephrology, Department of Medicine, University of California San 
      Francisco, San Francisco, CA, USA.
FAU - Breeden, Cynthia
AU  - Breeden C
AD  - Emory Transplant Center, Department of Surgery, School of Medicine, Emory 
      University, Atlanta, GA, USA.
FAU - Sanz, Ignacio
AU  - Sanz I
AD  - Department of Medicine, Division of Rheumatology, Lowance Center for Human 
      Immunology, Emory University, Atlanta, GA, USA.
FAU - Gibson, Greg
AU  - Gibson G
AD  - School of Biological Sciences, Georgia Institute of Technology, Atlanta, GA, USA.
FAU - Lee, F Eun-Hyung
AU  - Lee FE
AD  - Department of Medicine, Division of Pulmonary, Allergy, Critical Care, and Sleep 
      Medicine, Emory University, Atlanta, GA, USA; Department of Medicine, Division of 
      Rheumatology, Lowance Center for Human Immunology, Emory University, Atlanta, GA, 
      USA. Electronic address: f.e.lee@emory.edu.
LA  - eng
GR  - U01 AI141993/AI/NIAID NIH HHS/United States
GR  - UM1 AI109565/AI/NIAID NIH HHS/United States
GR  - R01 AI121252/AI/NIAID NIH HHS/United States
GR  - P01 AI125180/AI/NIAID NIH HHS/United States
GR  - U54 CA260563/CA/NCI NIH HHS/United States
GR  - P01 AI078907/AI/NIAID NIH HHS/United States
GR  - U19 AI110483/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20230624
PL  - United States
TA  - Cell Rep
JT  - Cell reports
JID - 101573691
RN  - 0 (Histocompatibility Antigens Class II)
SB  - IM
UOF - bioRxiv. 2023 Jan 20;:. PMID: 36711623
MH  - Adult
MH  - Humans
MH  - *Plasma Cells
MH  - *Bone Marrow
MH  - Antibody-Producing Cells/metabolism
MH  - Histocompatibility Antigens Class II/metabolism
MH  - Single-Cell Analysis
MH  - Bone Marrow Cells
PMC - PMC10391632
OTO - NOTNLM
OT  - CP: Immunology
OT  - TNF signaling through NFKB
OT  - heterogeneity and maturation
OT  - human bone marrow
OT  - long-lived plasma cell
OT  - single-cell sequencing
COIS- Declaration of interests F.E.L. is the founder of Micro-Bplex, Inc., serves on 
      the scientific board of Be Biopharma, and is a recipient of grants from the BMGF 
      and Genentech, Inc. I.S. has consulted for GSK, Pfizer, Kayverna, Johnson & 
      Johnson, Celgene, Bristol Myer Squibb, and Visterra. F.E.L, D.C.N., and I.S. are 
      inventors of the issued patents: 9/21/21 US 11,124766 B2 PCT/US2016/036650 and 
      9/21/21 US 11, 125757 B2 for the PC survival media.
EDAT- 2023/06/25 19:15
MHDA- 2023/07/31 06:42
PMCR- 2023/06/24
CRDT- 2023/06/25 12:36
PHST- 2022/09/02 00:00 [received]
PHST- 2022/12/28 00:00 [revised]
PHST- 2023/06/06 00:00 [accepted]
PHST- 2023/07/31 06:42 [medline]
PHST- 2023/06/25 19:15 [pubmed]
PHST- 2023/06/25 12:36 [entrez]
PHST- 2023/06/24 00:00 [pmc-release]
AID - S2211-1247(23)00693-9 [pii]
AID - 112682 [pii]
AID - 10.1016/j.celrep.2023.112682 [doi]
PST - ppublish
SO  - Cell Rep. 2023 Jul 25;42(7):112682. doi: 10.1016/j.celrep.2023.112682. Epub 2023 
      Jun 24.