TCF-1 upregulation identifies early innate lymphoid progenitors in the bone marrow.
The cellular and molecular events that drive the early development of innate lymphoid cells (ILCs) remain poorly understood. We show that the transcription factor TCF-1 is required for the efficient generation of all known adult ILC subsets and their precursors. Using novel reporter mice, we identified a new subset of early ILC progenitors (EILPs) expressing high amounts of TCF-1. EILPs lacked efficient T and B lymphocyte potential but efficiently gave rise to NK cells and all known adult helper ILC lineages, indicating that they are the earliest ILC-committed progenitors identified so far. Our results suggest that upregulation of TCF-1 expression denotes the earliest stage of ILC fate specification. The discovery of EILPs provides a basis for deciphering additional signals that specify ILC fate.
T-Cell Biology and Development Unit, Laboratory of Genome Integrity, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA.|Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Qi
Q
Yang
Department of Microbiology, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA.
Fengyin
F
Li
T-Cell Biology and Development Unit, Laboratory of Genome Integrity, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA.
Christelle
C
Harly
Department of Microbiology, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA.
Shaojun
S
Xing
T-Cell Biology and Development Unit, Laboratory of Genome Integrity, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA.
Longyun
L
Ye
Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Xuefeng
X
Xia
Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Haikun
H
Wang
Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Xinxin
X
Wang
Department of Microbiology, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA.
Shuyang
S
Yu
Department of Microbiology, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA.
Xinyuan
X
Zhou
CCR Collaborative Bioinformatics Resource, National Cancer Institute, Bethesda, Maryland, USA.
Maggie
M
Cam
Department of Microbiology, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA.
Hai-Hui
HH
Xue
T-Cell Biology and Development Unit, Laboratory of Genome Integrity, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA.
Avinash
A
Bhandoola
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology* / Q000276:immunology*; D002478:Cells, Cultured; D005434:Flow Cytometry; D007113:Immunity, Innate; D008214:Lymphocytes / Q000166:cytology* / Q000276:immunology*; D051379:Mice; D046228:Microarray Analysis; D051822:T Cell Transcription Factor 1 / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation
D051822:T Cell Transcription Factor 1