title: Signaling Networks among Stem Cell Precursors, Transit-Amplifying Progenitors, and their Niche in Developing Hair Follicles.
abstract: The hair follicle (HF) is a complex miniorgan that serves as an ideal model system to study stem cell (SC) interactions with the niche during growth and regeneration. Dermal papilla (DP) cells are required for SC activation during the adult hair cycle, but signal exchange between niche and SC precursors/transit-amplifying cell (TAC) progenitors that regulates HF morphogenetic growth is largely unknown. Here we use six transgenic reporters to isolate 14 major skin and HF cell populations. With next-generation RNA sequencing, we characterize their transcriptomes and define unique molecular signatures. SC precursors, TACs, and the DP niche express a plethora of ligands and receptors. Signaling interaction network analysis reveals a bird's-eye view of pathways implicated in epithelial-mesenchymal interactions. Using a systematic tissue-wide approach, this work provides a comprehensive platform, linked to an interactive online database, to identify and further explore the SC/TAC/niche crosstalk regulating HF growth.
authors.affiliation: Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Amélie
authors.initials: A
authors.lastname: Rezza
authors.affiliation: Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Pharmacology and Systems Therapeutics, BD2K-LINCS Data Coordination and Integration Center, Knowledge Management Center for Illuminating the Druggable Genome (KMC-IDG), Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Zichen
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Rachel
authors.initials: R
authors.lastname: Sennett
authors.affiliation: Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, ON M5S 3G9, Canada.
authors.forename: Wenlian
authors.initials: W
authors.lastname: Qiao
authors.affiliation: Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO 80309, USA.
authors.forename: Dongmei
authors.initials: D
authors.lastname: Wang
authors.affiliation: Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Heitman
authors.affiliation: Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Ka Wai
authors.initials: KW
authors.lastname: Mok
authors.affiliation: Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Carlos
authors.initials: C
authors.lastname: Clavel
authors.affiliation: Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO 80309, USA.
authors.forename: Rui
authors.initials: R
authors.lastname: Yi
authors.affiliation: Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, ON M5S 3G9, Canada.
authors.forename: Peter
authors.initials: P
authors.lastname: Zandstra
authors.affiliation: Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Pharmacology and Systems Therapeutics, BD2K-LINCS Data Coordination and Integration Center, Knowledge Management Center for Illuminating the Druggable Genome (KMC-IDG), Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Avi
authors.initials: A
authors.lastname: Ma'ayan
authors.affiliation: Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. Electronic address: michael.rendl@mssm.edu.
authors.forename: Michael
authors.initials: M
authors.lastname: Rendl
mesh_terms: D000818:Animals; D005434:Flow Cytometry; D018859:Hair Follicle / Q000378:metabolism*; D053547:Keratin-14 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008856:Microscopy, Fluorescence; D025341:Principal Component Analysis; D055758:SOX9 Transcription Factor / Q000235:genetics / Q000378:metabolism; D017423:Sequence Analysis, RNA; D015398:Signal Transduction / Q000235:genetics; D012867:Skin / Q000166:cytology / Q000378:metabolism*; D055153:Stem Cell Niche; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D059467:Transcriptome
chemical_list: D053547:Keratin-14; D055758:SOX9 Transcription Factor; C527932:SOX9 protein, human
keywords: big data; dermal papilla; epithelial-mesenchymal interactions; hair follicle; hair growth; progenitors; signaling networks; stem cell niche; stem cells; systems biology; transcriptomics