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Toll-Like Receptor 2 Expression on c-kit+ Cells Tracks the Emergence of Definitive Hematopoietic Progenitors in a Pre-Circulation Embryo

64 Pages Posted: 26 Feb 2019 Sneak Peek Status: Review Complete

See all articles by Jana Balounová

Jana Balounová

Czech Academy of Sciences, Institute of Molecular Genetics, Laboratory of Immunobiology; Czech Academy of Sciences, Institute of Molecular Genetics, Czech Centre for Phenogenomics & Laboratory of Transgenic Models of Diseases

Iva Šplíchalová

Czech Academy of Sciences, Institute of Molecular Genetics, Laboratory of Immunobiology; Charles University in Prague, Faculty of Science - BIOCEV, Department of Cell Biology

Martina Dobešová

Czech Academy of Sciences, Institute of Molecular Genetics, Laboratory of Immunobiology

Michal Kolář

Czech Academy of Sciences, Institute of Molecular Genetics, Laboratory of Genomics and Bioinformatics

Karel Fišer

Charles University in Prague, 2nd Faculty of Medicine, Childhood Leukaemia Investigation Prague

Jan Procházka

Czech Academy of Sciences, Institute of Molecular Genetics, Czech Centre for Phenogenomics & Laboratory of Transgenic Models of Diseases

Radislav Sedláček

Czech Academy of Sciences, Institute of Molecular Genetics, Czech Centre for Phenogenomics & Laboratory of Transgenic Models of Diseases

Andrea Jurisicova

Mount Sinai Hospital, Lunenfeld-Tanenbaum Research Institute

Hoon-ki Sung

University of Toronto - The Hospital for Sick Children - SickKids

Meritxell Alberich-Jorda

Czech Academy of Sciences, Institute of Molecular Genetics, Laboratory of Hematooncology

Dominik Filipp

Czech Academy of Sciences, Institute of Molecular Genetics, Laboratory of Immunobiology

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Abstract

Hematopoiesis in mammalian embryos proceeds through three successive waves of hematopoietic progenitors. Since their emergence is spatially and temporally overlapping and phenotypic markers are often shared, the specifics regarding their origin, development, lineage restriction and mutual relationships have not been fully determined. The identification of wave-specific markers would aid to resolve these uncertainties. Here, we show that Toll-like receptors (TLRs) are expressed during early embryogenesis. We provide phenotypic and functional evidence that the expression of TLR2 on E7.5 c-kit+ cells marks the emergence of erythro-myeloid progenitors (EMPs) and established that TLR2 engagement leads to the enhanced production of myeloid cells. Using in vivo fate mapping, we show that at E8.5 the Tlr2 locus is already active in emerging EMPs and in progenitors of adult hematopoietic stem cells (HSC). Together, these data demonstrate that the activation of Tlr2 locus tracks the earliest events in the process of EMP and HSC specification.

Suggested Citation

Balounová, Jana and Šplíchalová, Iva and Dobešová, Martina and Kolář, Michal and Fišer, Karel and Procházka, Jan and Sedláček, Radislav and Jurisicova, Andrea and Sung, Hoon-ki and Alberich-Jorda, Meritxell and Filipp, Dominik, Toll-Like Receptor 2 Expression on c-kit+ Cells Tracks the Emergence of Definitive Hematopoietic Progenitors in a Pre-Circulation Embryo (December 28, 2018). Available at SSRN: https://ssrn.com/abstract=3307530 or http://dx.doi.org/10.2139/ssrn.3307530
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Jana Balounová

Czech Academy of Sciences, Institute of Molecular Genetics, Laboratory of Immunobiology

Prague
Czech Republic

Czech Academy of Sciences, Institute of Molecular Genetics, Czech Centre for Phenogenomics & Laboratory of Transgenic Models of Diseases

Prague
Czech Republic

Iva Šplíchalová

Czech Academy of Sciences, Institute of Molecular Genetics, Laboratory of Immunobiology

Prague
Czech Republic

Charles University in Prague, Faculty of Science - BIOCEV, Department of Cell Biology

Prague
Czech Republic

Martina Dobešová

Czech Academy of Sciences, Institute of Molecular Genetics, Laboratory of Immunobiology

Prague
Czech Republic

Michal Kolář

Czech Academy of Sciences, Institute of Molecular Genetics, Laboratory of Genomics and Bioinformatics

Prague
Czech Republic

Karel Fišer

Charles University in Prague, 2nd Faculty of Medicine, Childhood Leukaemia Investigation Prague

Prague
Czech Republic

Jan Procházka

Czech Academy of Sciences, Institute of Molecular Genetics, Czech Centre for Phenogenomics & Laboratory of Transgenic Models of Diseases

Prague
Czech Republic

Radislav Sedláček

Czech Academy of Sciences, Institute of Molecular Genetics, Czech Centre for Phenogenomics & Laboratory of Transgenic Models of Diseases

Prague
Czech Republic

Andrea Jurisicova

Mount Sinai Hospital, Lunenfeld-Tanenbaum Research Institute

600 University Ave
Toronto, Ontario
Canada

Hoon-ki Sung

University of Toronto - The Hospital for Sick Children - SickKids

555 University Avenue
Toronto, Ontario M5G 1X8
Canada

Meritxell Alberich-Jorda

Czech Academy of Sciences, Institute of Molecular Genetics, Laboratory of Hematooncology

Prague
Czech Republic

Dominik Filipp (Contact Author)

Czech Academy of Sciences, Institute of Molecular Genetics, Laboratory of Immunobiology ( email )

Prague
Czech Republic

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