Embryonic origin of adult stem cells required for tissue homeostasis and regeneration
- Stowers Institute for Medical Research, United States
Abstract
Planarian neoblasts are pluripotent, adult somatic stem cells and lineage-primed progenitors required for production and maintenance of all differentiated cell types, including the germline. Neoblasts, originally defined as undifferentiated cells residing in the adult parenchyma, are frequently compared to embryonic stem cells yet their developmental origin remains obscure. We investigated the provenance of neoblasts during S. mediterranea embryogenesis, and report that neoblasts arise from an anarchic, cycling piwi-1+ population wholly responsible for production of all temporary and definitive organs during embryogenesis. Early embryonic piwi-1+ cells are molecularly and functionally distinct from neoblasts: they express unique cohorts of early embryo enriched transcripts and behave differently than neoblasts in cell transplantation assays. Neoblast lineages arise as organogenesis begins and are required for construction of all major organ systems during embryogenesis. These subpopulations are continuously generated during adulthood, where they act as agents of tissue homeostasis and regeneration.
Article and author information
Author details
Alejandro Sánchez Alvarado
Funding
National Institute of General Medical Sciences (R37GM057260-17)
- Alejandro Sánchez Alvarado
Howard Hughes Medical Institute
- Kai Lei
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Utpal Banerjee, University of California, Los Angeles, United States
Version history
- Received: August 30, 2016
- Accepted: January 4, 2017
- Accepted Manuscript published: January 10, 2017 (version 1)
- Version of Record published: February 6, 2017 (version 2)
Copyright
© 2017, Davies 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.
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Embryonic origin of adult stem cells required for tissue homeostasis and regeneration
eLife 6:e21052.
https://doi.org/10.7554/eLife.21052
Further reading
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Endothelial and skeletal muscle lineages arise from common embryonic progenitors. Despite their shared developmental origin, adult endothelial cells (ECs) and muscle stem cells (MuSCs; satellite cells) have been thought to possess distinct gene signatures and signaling pathways. Here, we shift this paradigm by uncovering how adult MuSC behavior is affected by the expression of a subset of EC transcripts. We used several computational analyses including single-cell RNA-seq (scRNA-seq) to show that MuSCs express low levels of canonical EC markers in mice. We demonstrate that MuSC survival is regulated by one such prototypic endothelial signaling pathway (VEGFA-FLT1). Using pharmacological and genetic gain- and loss-of-function studies, we identify the FLT1-AKT1 axis as the key effector underlying VEGFA-mediated regulation of MuSC survival. All together, our data support that the VEGFA-FLT1-AKT1 pathway promotes MuSC survival during muscle regeneration, and highlights how the minor expression of select transcripts is sufficient for affecting cell behavior.
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