TY - JOUR
T1 - Multi-tissue single-cell analysis deconstructs the complex programs of mouse natural killer and type 1 innate lymphoid cells in tissues and circulation
AU - McFarland, Adelle P.
AU - Yalin, Adam
AU - Wang, Shuang Yin
AU - Cortez, Victor S.
AU - Landsberger, Tomer
AU - Sudan, Raki
AU - Peng, Vincent
AU - Miller, Hannah L.
AU - Ricci, Biancamaria
AU - David, Eyal
AU - Faccio, Roberta
AU - Amit, Ido
AU - Colonna, Marco
N1 - Funding Information:
We thank the Flow Cytometry & FACS Core at the WUSM Department of Pathology & Immunology for cell sorting assistance and guidance, as well as Susan Gilfillan for helpful suggestions. M.C. is supported by the NIH (grants R01 DE025884 , 1R01 AI134236-01 , R01 124699 and R01 AI134035 ). I.A. is an Eden and Steven Romick Professorial Chair and is supported by Merck KGaA (Darmstadt, Germany), the Chan Zuckerberg Initiative (CZI), an HHMI International Scholar award, European Research Council consolidator grant (ERC-COG) 724471-HemTree2.0 , the ISF Israel Precision Medicine Program (IPMP) 607/20 (grant P128245 ), an SCA award of the Wolfson Foundation and Family Charitable Trust , the Thompson Family Foundation , an MRA Established Investigator Award ( 509044 ), the Israel Science Foundation (703/15), the Ernest and Bonnie Beutler Research Program for Excellence in Genomic Medicine , the Helen and Martin Kimmel award for innovative investigation, the NeuroMac DFG /Transregional Collaborative Research Center Grant, the International Progressive MS Alliance/NMSS ( PA-1604 08459 ), and an Abney Foundation grant. A.P.M was supported by NIH grant T32 DK077653-27 . S.-Y.W. is an EMBO long-term fellow ( ALTF 263-2018 ) and is supported by an NWO Rubicon award ( 019.181EN.038 ). V.S.C. is supported by the Cancer Research Institute.
Funding Information:
We thank the Flow Cytometry & FACS Core at the WUSM Department of Pathology & Immunology for cell sorting assistance and guidance, as well as Susan Gilfillan for helpful suggestions. M.C. is supported by the NIH (grants R01 DE025884, 1R01 AI134236-01, R01 124699 and R01 AI134035). I.A. is an Eden and Steven Romick Professorial Chair and is supported by Merck KGaA (Darmstadt, Germany), the Chan Zuckerberg Initiative (CZI), an HHMI International Scholar award, European Research Council consolidator grant (ERC-COG) 724471-HemTree2.0, the ISF Israel Precision Medicine Program (IPMP) 607/20 (grant P128245), an SCA award of the Wolfson Foundation and Family Charitable Trust, the Thompson Family Foundation, an MRA Established Investigator Award (509044), the Israel Science Foundation (703/15), the Ernest and Bonnie Beutler Research Program for Excellence in Genomic Medicine, the Helen and Martin Kimmel award for innovative investigation, the NeuroMac DFG/Transregional Collaborative Research Center Grant, the International Progressive MS Alliance/NMSS (PA-1604 08459), and an Abney Foundation grant. A.P.M was supported by NIH grant T32 DK077653-27. S.-Y.W. is an EMBO long-term fellow (ALTF 263-2018) and is supported by an NWO Rubicon award (019.181EN.038). V.S.C. is supported by the Cancer Research Institute. Conceptualization, A.Y. V.S.C. I.A. and M.C.; methodology, A.Y. V.S.C. S.-Y.W. B.R. R.F. I.A. and M.C.; validation, A.P.M. R.S. V.P. and H.M.; formal analysis, A.P.M. A.Y. S.-Y.W. E.D. and T.L.; investigation, A.P.M. A.Y. V.C. S.-Y.W. H.M. and B.R.; writing, A.P.M. A.Y. I.A. and M.C.; visualization, A.P.M. A.Y. and S.-Y.W.; funding acquisition, I.A. and M.C. M.C. receives research support from Pfizer and NGM Biopharmaceuticals, is a scientific advisory board member of Vigil Neuroscience and NGM Biopharmaceuticals, and is a consultant of Cell Signaling Technologies. I.A. is a scientific advisory board member of Neogene Therapeutics and CELLINK.
Publisher Copyright:
© 2021 Elsevier Inc.
PY - 2021/6/8
Y1 - 2021/6/8
N2 - Natural killer (NK) cells and type 1 innate lymphoid cells (ILC1s) are heterogenous innate lymphocytes broadly defined in mice as Lin−NK1.1+NKp46+ cells that express the transcription factor T-BET and produce interferon-γ. The ILC1 definition primarily stems from studies on liver and small intestinal populations. However, NK1.1+NKp46+ cells in the salivary glands, uterus, adipose, and other tissues exhibit nonuniform programs that differ from those of liver or intestinal ILC1s or NK cells. Here, we performed single-cell RNA sequencing on murine NK1.1+NKp46+ cells from blood, spleen, various tissues, and solid tumors. We identified gene expression programs of tissue-specific ILC1s, tissue-specific NK cells, and non-tissue-specific populations in blood, spleen, and other tissues largely corresponding to circulating cells. Moreover, we found that circulating NK cell programs were reshaped in tumor-bearing mice. Core programs of circulating and tumor NK cells paralleled conserved human NK cells signatures, advancing our understanding of the human NK-ILC1 spectrum.
AB - Natural killer (NK) cells and type 1 innate lymphoid cells (ILC1s) are heterogenous innate lymphocytes broadly defined in mice as Lin−NK1.1+NKp46+ cells that express the transcription factor T-BET and produce interferon-γ. The ILC1 definition primarily stems from studies on liver and small intestinal populations. However, NK1.1+NKp46+ cells in the salivary glands, uterus, adipose, and other tissues exhibit nonuniform programs that differ from those of liver or intestinal ILC1s or NK cells. Here, we performed single-cell RNA sequencing on murine NK1.1+NKp46+ cells from blood, spleen, various tissues, and solid tumors. We identified gene expression programs of tissue-specific ILC1s, tissue-specific NK cells, and non-tissue-specific populations in blood, spleen, and other tissues largely corresponding to circulating cells. Moreover, we found that circulating NK cell programs were reshaped in tumor-bearing mice. Core programs of circulating and tumor NK cells paralleled conserved human NK cells signatures, advancing our understanding of the human NK-ILC1 spectrum.
KW - EOMES
KW - HOBIT
KW - TCF-1
KW - glycolysis
KW - innate lymphoid cells
KW - natural killer cells
KW - single-cell RNA sequencing
KW - tissue
KW - transcription factor
KW - tumor
UR - http://www.scopus.com/inward/record.url?scp=85108026677&partnerID=8YFLogxK
U2 - 10.1016/j.immuni.2021.03.024
DO - 10.1016/j.immuni.2021.03.024
M3 - Article
C2 - 33945787
AN - SCOPUS:85108026677
SN - 1074-7613
VL - 54
SP - 1320-1337.e4
JO - Immunity
JF - Immunity
IS - 6
ER -