Biology subjects

Hack, S. J.

Publications and source records attributed to Hack, S. J..

3 recordsLinked to original sources

bioRxiv2025

Planar cell polarity signaling controls cell division symmetry to promote termination of adult tissue regeneration

Tissue formation is coordinated by cell-intrinsic and cell-extrinsic signals across space and time, yet how self-limiting growth is controlled remains mysterious. Here, we leveraged the highly regenerative planarian Schmidtea mediterranea to identify molecular regulators of endogenous growth termination in adults, where unchecked growth can promote carcinogenesis. We identified the Planar Cell Polarity (PCP) pathway as a key regulator of body-wide regenerative growth through control of stem cell division symmetry. Following PCP pathway inhibition, widespread tissue hyperplasia occurred weeks after regeneration normally finishes. Importantly, this was due to progenitor expansion and depletion of adult tspan-1+ pluripotent stem cells capable of whole-body regeneration. Using transcriptional analysis of regenerating animals over time, we identified that control of stem cell fate by changes in cell division symmetry is a potential growth termination mechanism. While symmetric divisions maintain the stem cell pool in adult planaria, upon PCP loss, the number of asymmetrically dividing cells increases, driving stem cell depletion and excessive tissue differentiation. Our data suggest that PCP signaling regulates stem cell maintenance and fate decisions during self-limiting growth. Summary StatementHere, we show that Planar Cell Polarity (PCP) signaling regulates stem cell division symmetry to control termination of adult tissue regeneration in planarians.

developmental biology↗

bioRxiv2024

Temporal Transcriptomic Profiling of the Developing Xenopus laevis Eye

Retinal progenitor cells (RPCs) are a multipotent and highly proliferative population that give rise to all retinal cell types during organogenesis. Defining their molecular signature is a key step towards identifying suitable approaches to treat visual impairments. Here, we performed RNA-sequencing of whole eyes from Xenopus at three embryonic stages and used differential expression analysis to define the transcriptomic profiles of optic tissues containing proliferating and differentiating RPCs during retinogenesis. Gene Ontology and KEGG pathway analyses showed that genes associated with developmental pathways (including Wnt and Hedgehog signaling) were upregulated during the period of active RPC proliferation in early retinal development (Nieuwkoop Faber st. 24 and 27). Developing eyes had dynamic expression profiles and shifted to enrichment for metabolic processes and phototransduction during RPC progeny specification and differentiation (st. 35). Furthermore, conserved adult eye regeneration genes were also expressed during early retinal development including sox2, pax6, nrl, and Notch signaling components. The eye transcriptomic profiles presented here span RPC proliferation to retinogenesis and included regrowth-competent stages. Thus, our dataset provides a rich resource to uncover molecular regulators of RPC activity and will allow future studies to address regulators of RPC proliferation during eye repair and regrowth.

developmental biology↗

bioRxiv2022

Reactive Oxygen Species Signaling Differentially Controls Wound Healing and Regeneration

Reactive oxygen species (ROS), such as hydrogen peroxide, are conserved and critical components of both wound healing and regeneration. Even though millions are affected each year by poor wound healing and an inability to restore functional tissue, how the same ROS-mediated signaling regulates these two different processes is not fully understood. Here, we investigate the role(s) of ROS during planarian wound healing and regeneration. We show ROS accumulate after injury and are required for wound closure (by promoting cytoskeletal movements) and regrowth (by promoting blastema formation). We found that different threshold levels of ROS regulate separate downstream targets to control wound healing (jun-1) versus regeneration (hsp70). By only manipulating ROS levels, we were able to control which injury-induced program was initiated: failure to close (chronic wound), healing only (no blastema), or full regeneration. Our results demonstrate that healing versus regenerative outcomes are based on differential ROS-mediated gene expression soon after injury. This study highlights ROS signaling as a potential therapeutic means to control wound repair mechanisms in multiple contexts. Therefore, investigating the mechanisms by which ROS control different tissue repair processes will be necessary not only for regenerative medicine but to improve clinical outcomes for chronic wounds and fibrosis.

developmental biology↗