1. Stem Cells and Regenerative Medicine
Download icon

Embryonic attenuated Wnt/β-catenin signaling defines niche location and long-term stem cell fate in hair follicle

  1. Zijian Xu
  2. Wenjie Wang
  3. Kaiju Jiang
  4. Zhou Yu
  5. Huagnwei Huang
  6. Fengchao Wang
  7. Bin Zhou
  8. Ting Chen  Is a corresponding author
  1. National Institute of Biological Sciences, China
Research Article
  • Cited 29
  • Views 4,446
  • Annotations
Cite this article as: eLife 2015;4:e10567 doi: 10.7554/eLife.10567

Abstract

Long-term adult stem cells sustain tissue regeneration throughout the lifetime of an organism. They were hypothesized to originate from embryonic progenitor cells that acquire long-term self-renewal ability and multipotency at the end of organogenesis. The process through which this is achieved often remains unclear. Here, we discovered that long-term hair follicle stem cells arise from embryonic progenitor cells occupying a niche location that is defined by attenuated Wnt/β-catenin signaling. Hair follicle initiation is marked by placode formation, which depends on the activation of Wnt/β-catenin signaling. Soon afterwards, a region with attenuated Wnt/β-catenin signaling emerges in the upper follicle. Embryonic progenitor cells residing in this region gain expression of adult stem cell markers and become definitive long-term hair follicle stem cells at the end of organogenesis. Attenuation of Wnt/β-catenin signaling is a prerequisite for hair follicle stem cell specification because it suppresses Sox9, which is required for stem cell formation.

Article and author information

Author details

  1. Zijian Xu

    National Institute of Biological Sciences, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  2. Wenjie Wang

    National Institute of Biological Sciences, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  3. Kaiju Jiang

    National Institute of Biological Sciences, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  4. Zhou Yu

    National Institute of Biological Sciences, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  5. Huagnwei Huang

    National Institute of Biological Sciences, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  6. Fengchao Wang

    National Institute of Biological Sciences, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  7. Bin Zhou

    National Institute of Biological Sciences, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  8. Ting Chen

    National Institute of Biological Sciences, Beijing, China
    For correspondence
    chenting@nibs.ac.cn
    Competing interests
    The authors declare that no competing interests exist.

Ethics

Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Biological Sciences. All of the animals were handled according to the guidelines of the Chinese law regulating the usage of experimental animals and the protocols (M0020) approved by the Committee on the Ethics of Animal Experiments of the National Institute of Biological Sciences, Beijing. All surgery was performed under combination anesthesia involving isoflurane and remifentanyl and every effort was made to minimize discomfort and suffering.

Reviewing Editor

  1. Janet Rossant, University of Toronto, Canada

Publication history

  1. Received: August 2, 2015
  2. Accepted: December 13, 2015
  3. Accepted Manuscript published: December 14, 2015 (version 1)
  4. Version of Record published: February 4, 2016 (version 2)

Copyright

© 2015, Xu et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 4,446
    Page views
  • 1,215
    Downloads
  • 29
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Download citations (links to download the citations from this article in formats compatible with various reference manager tools)

Open citations (links to open the citations from this article in various online reference manager services)

Further reading

    1. Developmental Biology
    2. Stem Cells and Regenerative Medicine
    Dongsheng Guo et al.
    Tools and Resources

    Skeletal muscle myoblasts (iMyoblasts) were generated from human induced pluripotent stem cells (iPSCs) using an efficient and reliable transgene-free induction and stem cell selection protocol. Immunofluorescence, flow cytometry, qPCR, digital RNA expression profiling, and scRNA-Seq studies identify iMyoblasts as a PAX3+/MYOD1+ skeletal myogenic lineage with a fetal-like transcriptome signature, distinct from adult muscle biopsy myoblasts (bMyoblasts) and iPSC-induced muscle progenitors. iMyoblasts can be stably propagated for >12 passages or 30 population doublings while retaining their dual commitment for myotube differentiation and regeneration of reserve cells. iMyoblasts also efficiently xenoengrafted into irradiated and injured mouse muscle where they undergo differentiation and fetal-adult MYH isoform switching, demonstrating their regulatory plasticity for adult muscle maturation in response to signals in the host muscle. Xenograft muscle retains PAX3+ muscle progenitors and can regenerate human muscle in response to secondary injury. As models of disease, iMyoblasts from individuals with Facioscapulohumeral Muscular Dystrophy revealed a previously unknown epigenetic regulatory mechanism controlling developmental expression of the pathological DUX4 gene. iMyoblasts from Limb-Girdle Muscular Dystrophy R7 and R9 and Walker Warburg Syndrome patients modeled their molecular disease pathologies and were responsive to small molecule and gene editing therapeutics. These findings establish the utility of iMyoblasts for ex vivo and in vivo investigations of human myogenesis and disease pathogenesis and for the development of muscle stem cell therapeutics.

    1. Stem Cells and Regenerative Medicine
    Mychel RPT Morais et al.
    Research Article

    Basement membranes (BMs) are complex macromolecular networks underlying all continuous layers of cells. Essential components include collagen IV and laminins, which are affected by human genetic variants leading to a range of debilitating conditions including kidney, muscle, and cerebrovascular phenotypes. We investigated the dynamics of BM assembly in human pluripotent stem cell-derived kidney organoids. We resolved their global BM composition and discovered a conserved temporal sequence in BM assembly that paralleled mammalian fetal kidneys. We identified the emergence of key BM isoforms, which were altered by a pathogenic variant in COL4A5. Integrating organoid, fetal and adult kidney proteomes we found dynamic regulation of BM composition through development to adulthood, and with single-cell transcriptomic analysis we mapped the cellular origins of BM components. Overall, we define the complex and dynamic nature of kidney BM assembly and provide a platform for understanding its wider relevance in human development and disease.