Identification of a Human Natural Killer Cell Lineage-Restricted Progenitor in Fetal and Adult Tissues.
Natural killer (NK) cells are cytotoxic lymphocytes and play a vital role in controlling viral infections and cancer. In contrast to B and T lymphopoiesis where cellular and regulatory pathways have been extensively characterized, the cellular stages of early human NK cell commitment remain poorly understood. Here we demonstrate that a Lin(-)CD34(+)CD38(+)CD123(-)CD45RA(+)CD7(+)CD10(+)CD127(-) population represents a NK lineage-restricted progenitor (NKP) in fetal development, umbilical cord blood, and adult tissues. The newly identified NKP has robust NK cell potential both in vitro and in vivo, generates functionally cytotoxic NK cells, and lacks the ability to produce T cells, B cells, myeloid cells, and innate lymphoid-like cells (ILCs). Our findings identify an early step to human NK cell commitment and provide new insights into the human hematopoietic hierarchy.
Lund Research Center for Stem Cell Biology and Cell Therapy, Lund University, 221 84 Lund, Sweden.
Virginie M
VM
Renoux
Lund Research Center for Stem Cell Biology and Cell Therapy, Lund University, 221 84 Lund, Sweden; Division of Molecular Hematology, Department of Laboratory Medicine, Lund University, 221 84 Lund, Sweden.
Alya
A
Zriwil
Lund Research Center for Stem Cell Biology and Cell Therapy, Lund University, 221 84 Lund, Sweden.
Claudia
C
Peitzsch
Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, 141 86 Stockholm, Sweden.
Jakob
J
Michaëlsson
Department of Otorhinolaryngology, Karolinska University Hospital Huddinge and CLINTEC, Karolinska Institutet, 141 86 Stockholm, Sweden.
Danielle
D
Friberg
Lund Research Center for Stem Cell Biology and Cell Therapy, Lund University, 221 84 Lund, Sweden; Division of Molecular Hematology, Department of Laboratory Medicine, Lund University, 221 84 Lund, Sweden.
Shamit
S
Soneji
Lund Research Center for Stem Cell Biology and Cell Therapy, Lund University, 221 84 Lund, Sweden; Division of Molecular Hematology, Department of Laboratory Medicine, Lund University, 221 84 Lund, Sweden. Electronic address: ewa.sitnicka@med.lu.se.
Ewa
E
Sitnicka
D000328:Adult; D015703:Antigens, CD / Q000378:metabolism; D002454:Cell Differentiation; D019070:Cell Lineage; D003602:Cytotoxicity, Immunologic; D005312:Fetal Blood / Q000166:cytology*; D047109:Fetal Development; D005333:Fetus / Q000166:cytology*; D006410:Hematopoiesis / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate; D016130:Immunophenotyping; D007694:Killer Cells, Natural / Q000502:physiology*; D054503:Lymphoid Progenitor Cells / Q000502:physiology*
D015703:Antigens, CD