Faculty Collaboration Database

Heterogeneity of human bone marrow and blood natural killer cells defined by single-cell transcriptome. Nat Commun 2019 Sep 02;10(1):3931

Date

09/04/2019

Pubmed ID

31477722

Pubmed Central ID

PMC6718415

DOI

10.1038/s41467-019-11947-7

Scopus ID

2-s2.0-85071610251 (requires institutional sign-in at Scopus site)   124 Citations

Abstract

Natural killer (NK) cells are critical to both innate and adaptive immunity. However, the development and heterogeneity of human NK cells are yet to be fully defined. Using single-cell RNA-sequencing technology, here we identify distinct NK populations in human bone marrow and blood, including one population expressing higher levels of immediate early genes indicative of a homeostatic activation. Functionally matured NK cells with high expression of CX3CR1, HAVCR2 (TIM-3), and ZEB2 represents terminally differentiated status with the unique transcriptional profile. Transcriptomic and pseudotime analyses identify a transitional population between CD56^bright and CD56^dim NK cells. Finally, a donor with GATA2^T354M mutation exhibits reduced percentage of CD56^bright NK cells with altered transcriptome and elevated cell death. These data expand our understanding of the heterogeneity and development of human NK cells.

Author List

Yang C, Siebert JR, Burns R, Gerbec ZJ, Bonacci B, Rymaszewski A, Rau M, Riese MJ, Rao S, Carlson KS, Routes JM, Verbsky JW, Thakar MS, Malarkannan S

Authors

Karen-Sue B. Carlson MD, PhD Associate Professor in the Medicine department at Medical College of Wisconsin
Subramaniam Malarkannan PhD Professor in the Medicine department at Medical College of Wisconsin
Sridhar Rao MD, PhD Associate Professor in the Pediatrics department at Medical College of Wisconsin
Amy Rymaszewski PhD Research Scientist I in the Pediatrics department at Medical College of Wisconsin
James Verbsky MD, PhD Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Bone Marrow
Bone Marrow Cells
CD56 Antigen
CX3C Chemokine Receptor 1
Genetic Heterogeneity
Hepatitis A Virus Cellular Receptor 2
Humans
Killer Cells, Natural
Single-Cell Analysis
Transcriptome
Zinc Finger E-box Binding Homeobox 2