Developmental origin and induction processes of hair follicle stem cells



The coordination of stem cell proliferation and differentiation is central to tissue development and maintenance. During mammalian epidermal development, different stem cell compartments are induced from seemingly homogeneous epidermal precursors, but the mechanisms that regulate stem cell induction remain elusive, mainly due to the lack of specific markers that exclusively label stem cell progenitors. By combining two marker-independent single-cell methods, namely the single-cell resolution 3D live imaging and single-cell transcriptomics, we investigate the molecular and cellular mechanisms underlying the induction of a variety of mouse hair follicle epidermal stem cells. We obtained high-spatiotemporal resolution live imaging data of epidermal cells in ex vivo developing hair follicles and identified the early developmental origin and lineages of follicle epidermal cells. Stem cell progenitors were originated from the basal epidermal cells located at the periphery of basal placode, but not from the previously reported suprabasal placode cells. Origins of different epidermal cell lineages were located in the basal placode in a concentric manner. Our single-cell transcriptome analysis of developing hair follicles identified the unique transcriptional signatures, markers and transcriptional dynamics of stem cell progenitors. We are now integrating the imaging and transcriptome data to create the first atlas of cellular dynamics and transcriptional changes that take place during the stem cell induction processes.


Hironobu Fujiwara is a Team Leader at the RIKEN Biosystems Dynamics Research in Kobe, Japan. He obtained his BSc in pharmacy from Kyoto Pharmaceutical University, and went on to receive his M.S. and Ph. D. from Osaka University, with Kiyotoshi Sekiguchi, the latter in 2003 for his work on the purification and characterization of the human laminin-8 protein. From 2003 to 2007, he served as a postdoctoral researcher at the Osaka University Institute for Protein research, with support from the ERATO Sekiguchi Biomatrix Signaling Project (2003 – 2006). He studied the role of the basement membrane in regulating mouse gastrulation using embryoid bodies. He then moved to the Cancer Research UK Cambridge Research Institute, where he completed a second postdoctoral fellowship with Fiona Watt. His study in the UK was focused on the role of the specialized basement membrane in the interaction between hair follicle stem cells and muscles. In 2012, he returned to Japan to take a position as a Team Leader at the RIKEN Center for Developmental Biology (CDB). His current research interests include the reciprocal interactions between tissue stem cells and their microenvironments, especially the extracellular matrix, in skin morphogenesis and regeneration.