Drosophila hematopoiesis bears striking resemblance with that of vertebrates, both in the context of distinct phases and the signaling molecules. Even though, there has been no evidence of Hematopoietic stem cells (HSCs) in Drosophila, the larval lymph gland with its Hedgehog dependent progenitors served as an invertebrate model of progenitor biology. Employing lineage-tracing analyses, we have now identified Notch expressing HSCs in the first instar larval lymph gland. Our studies clearly establish the hierarchical relationship between Notch expressing HSCs and the previously described Domeless expressing progenitors. These HSCs require Decapentapelagic (Dpp) signal from the hematopoietic niche for their maintenance in an identical manner to vertebrate aorta-gonadal-mesonephros (AGM) HSCs. Thus, this study not only extends the conservation across these divergent taxa, but also provides a new model that can be exploited to gain better insight into the AGM related Hematopoietic stem cells (HSCs).
- Lolitika Mandal
- Nidhi Sharma Dey
- Parvathy Ramesh
- Mayank Chugh
- Sudip Mandal
- Lolitika Mandal
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
- Yukiko M Yamashita, University of Michigan, United States
- Received: May 30, 2016
- Accepted: October 25, 2016
- Accepted Manuscript published: October 26, 2016 (version 1)
- Accepted Manuscript updated: October 31, 2016 (version 2)
- Version of Record published: November 23, 2016 (version 3)
- Version of Record updated: November 30, 2016 (version 4)
- Version of Record updated: September 11, 2019 (version 5)
© 2016, Dey 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.
In vitro culture systems that structurally model human myogenesis and promote PAX7+ myogenic progenitor maturation have not been established. Here we report that human skeletal muscle organoids can be differentiated from induced pluripotent stem cell lines to contain paraxial mesoderm and neuromesodermal progenitors and develop into organized structures reassembling neural plate border and dermomyotome. Culture conditions instigate neural lineage arrest and promote fetal hypaxial myogenesis toward limb axial anatomical identity, with generation of sustainable uncommitted PAX7 myogenic progenitors and fibroadipogenic (PDGFRa+) progenitor populations equivalent to those from the second trimester of human gestation. Single-cell comparison to human fetal and adult myogenic progenitor /satellite cells reveals distinct molecular signatures for non-dividing myogenic progenitors in activated (CD44High/CD98+/MYOD1+) and dormant (PAX7High/FBN1High/SPRY1High) states. Our approach provides a robust 3D in vitro developmental system for investigating muscle tissue morphogenesis and homeostasis.