Biology subjects

Reddien, P. W.

Publications and source records attributed to Reddien, P. W..

3 recordsLinked to original sources

bioRxiv2026

Lack of specificity of progenitor responses to injury in regeneration

Regeneration is the process by which organisms replace lost body parts. How cell-type production is tailored to match the identity of missing tissues is a central problem of regeneration. Here, we investigated the specificity of planarian stem-cell responses to the identity of missing tissues following injury. Proximal injury not affecting the mature tissue nonetheless drives increased cell incorporation into brain neurons, ventral nerve cords, pharynx muscle and neurons. Following direct injury, peripheral neurons show a spatially imprecise, generic amplification of incorporation relative to the injury; body-wall muscle incorporation was amplified, with decreased incorporation at wound-distal sites in favor of increased incorporation wound-proximally. By contrast, essentially no stem-cell division contributes to initial epidermal regeneration, instead post-mitotic progenitors supply the wound. Amplification of epidermal incorporation following injury does occur weeks after injury, including to uninjured regions. These results indicate that the identity of the missing mature tissue is not required in determining the stem-cell response to injury. We suggest that planarian regeneration specificity involves a combination of ongoing cell turnover, wound-associated amplification of stem-cells, and spatially broad neoblast specification zones.

developmental biology↗

bioRxiv2025

map3k1 is required for spatial restriction of progenitor differentiation in planarians

Planarian regeneration and tissue turnover involve fate specification in pluripotent stem cells called neoblasts. Neoblasts select fates through the expression of fate-specific transcription factors (FSTFs), generating specialized neoblasts. Specialized neoblasts are spatially intermingled and can be dispersed broadly, frequently being present far from their target tissue. The post-mitotic progeny of neoblasts, serving as progenitors, can migrate and differentiate into mature cell types. Pattern formation is thus strongly influenced by the migratory assortment and differentiation of fate-specified progenitors in precise locations, which we refer to as progenitor targeting. This central step of pattern maintenance and formation, however, is poorly understood. Here, we describe a requirement for the conserved map3k1 gene in targeting, restricting post-mitotic progenitor differentiation to precise locations. RNAi of map3k1 causes ectopic differentiation of eye progenitors along their migratory path, resulting in dispersed, ectopic eye cells and eyes. Other neural tissues similarly display ectopic posterior differentiation and ectopic pharynx cells emerge dispersed laterally and anteriorly in map3k1 RNAi animals. Ectopic differentiated cells are also found within the incorrect organs after map3k1 RNAi, and ultimately, teratomas form. These findings implicate map3k1 signaling in controlling the positional regulation of progenitor behavior - restricting progenitor differentiation to targeted locations in response to external cues in the local tissue environment.

developmental biology↗

bioRxiv2021

m6A is required for resolving progenitor identity during planarian stem cell differentiation

Regeneration requires accurate production of missing cell lineages. Cell production is driven by changes to gene expression, which is shaped by multiple layers of regulation. Here, we find that the ubiquitous mRNA base-modification, m6A, is required for proper cell fate choice and cellular maturation in planarian stem cells (neoblasts). We mapped m6A-enriched regions in 7,600 planarian genes, and found that perturbation of the m6A pathway resulted in progressive deterioration of tissues and death. Using single cell RNA sequencing of >20,000 cells following perturbation of the pathway, we discovered that m6A negatively regulates transcription of histone variants, and that inhibition of the pathway resulted in accumulation of undifferentiated cells throughout the animal in an abnormal transcriptional state. Analysis of >1000 planarian gene expression datasets revealed that the inhibition of the chromatin modifying complex NuRD had almost indistinguishable consequences, unraveling an unappreciated link between m6A and chromatin modifications. Our findings reveal that m6A is critical for planarian stem cell homeostasis and gene regulation in regeneration.

developmental biology↗