Biology subjects

Hamm, M.

Publications and source records attributed to Hamm, M..

5 recordsLinked to original sources

bioRxiv2026

BRN2 preserves the melanocyte lineage following ionizing radiation

Adult stem cells maintain tissue homeostasis, but mechanisms preserving their integrity under stress remain incompletely understood. Here, we identify BRN2 (POU3F2), previously implicated in neuronal development, reprogramming of fibroblasts to neurons and in melanoma proliferation, migration and DNA-damage responses, as a key guardian of melanocyte stem cells. Remarkably, we reveal that while Brn2-deficient mice maintain their McSC compartment and normal pigmentation for up to 95 weeks, in contrast, rapid, dose-dependent, permanent hair depigmentation associated with the disappearance of detectable McSCs and differentiated melanocytes occurs in Brn2 KO mice exposed to ionizing radiation but not in WT mice. Importantly, our results indicate that in human follicular melanocytes BRN2 activity in melanocyte stem cells (McSCs) declines with age and that Brn2 promotes melanocyte stem cell regeneration by restraining stress-induced melanocytic differentiation. Our findings establish a previously unrecognized in vivo requirement for BRN2 in preserving the integrity of the melanocyte lineage following ionizing radiation, revealing a stress-dependent function distinct from its largely dispensable role in steady-state McSC maintenance.

cell biology↗

bioRxiv2021

BRN2 is a non-canonical melanoma tumor-suppressor

While the major drivers of melanoma initiation, including activation of NRAS/BRAF and loss of PTEN or CDKN2A, have been identified, the role of key transcription factors that impose altered transcriptional states in response to deregulated signaling is not well understood. The POU domain transcription factor BRN2 is a key regulator of melanoma invasion, yet its role in melanoma initiation remains unknown. Here, we show that BRN2 haplo-insufficiency is sufficient to promote melanoma initiation and metastasis, acting as a non-canonical tumor suppressor. Mechanistically, BRN2 directly modulates PTEN expression, and PI3K signaling, to drive tumor initiation and progression. Collectively our results reveal that somatic deletion of one BRN2 allele elicits melanoma initiation and progression. SIGNIFICANCEHere, we report frequent mono-allelic loss of the transcription factor BRN2 in human cutaneous melanoma metastases. We developed a mouse model for Brn2-deficient melanoma based on the most common alterations (BrafV600E and Pten loss) in human melanoma and established the role of Brn2 as a functional regulator of tumor initiation, tumor growth, and the formation of metastases in vivo. Mechanistically, BRN2 loss increases PI3K-signaling through PTEN repression, either via MITF induction or not. Overall, we describe a novel tumor suppressor of high prevalence in human melanoma that regulates several steps of in vivo melanomagenesis through two previously unknown molecular mechanisms.

cancer biology↗

bioRxiv2020

The regulatory landscape of Arabidopsis thaliana roots at single-cell resolution

In plants, chromatin accessibility - the primary mark of regulatory DNA - is relatively static across tissues and conditions. This scarcity of accessible sites that are dynamic or tissue-specific may be due in part to tissue heterogeneity in previous bulk studies. To assess the effects of tissue heterogeneity, we apply single-cell ATAC-seq to A. thaliana roots and identify thousands of differentially accessible sites, sufficient to resolve all major cell types of the root. However, even this vast increase relative to bulk studies in the number of dynamic sites does not resolve the poor correlation at individual loci between accessibility and expression. Instead, we find that the entirety of a cells regulatory landscape and its transcriptome each capture cell type identity independently. We leverage this shared information on cell identity to integrate accessibility and transcriptome data in order to characterize developmental progression, endoreduplication and cell division in the root. We further use the combined data to characterize cell type-specific motif enrichments of large transcription factor families and to link the expression of individual family members to changing accessibility at specific loci, taking the first steps toward resolving the direct and indirect effects that shape gene expression. Our approach provides an analytical framework to infer the gene regulatory networks that execute plant development.

genomics↗

bioRxiv2020

BrphyB is critical for rapid recovery to darkness in mature Brassica rapa leaves

Crop biomass and yield are tightly linked to how the light signaling network translates information about the environment into allocation of resources, including photosynthates. Once activated, the phytochrome (phy) class of photoreceptors signal and re-deploy carbon resources to alter growth, plant architecture, and reproductive timing. Brassica rapa has been used as a crop model to test for conservation of the phytochrome-carbon network. B. rapa phyB mutants have significantly decreased or absent CO2-stimulated growth responses in seedlings, and adult plants have reduced chlorophyll levels, photosynthetic rate, stomatal index, and seed yield. Here, we examine the transcriptomic response of adult wild-type and BrphyB leaves to darkening and recovery in light. Three days of darkness was sufficient to elicit a response in wild type leaves suggesting a shift from carbon fixation and nutrient acquisition to active redistribution of cellular resources. Upon a return to light, wild-type leaves appeared to transcriptionally return to a pre-darkness state restoring a focus on nutrient acquisition. Overall, BrphyB mutant plants have a similar response with key differences in genes involved in photosynthesis and light response which deviate from the wild type transcriptional dynamics. Genes targeted to the chloroplast are especially affected. Adult BrphyB mutant plants had fewer, larger chloroplasts, further linking phytochromes, chloroplast development, photosynthetic deficiencies and optimal resource allocation.

plant biology↗

bioRxiv2019

The concerted emergence of well-known spatial and temporal ecological patterns in an evolutionary food web model in space

Ecological systems show a variety of characteristic patterns of biodiversity in space and time. It is a challenge for theory to find models that can reproduce and explain the observed patterns. Since the advent of island biogeography these models revolve around speciation, dispersal, and extinction, but they usually neglect trophic structure. Here, we propose and study a spatially extended evolutionary food web model that allows us to study large spatial systems with several trophic layers. Our computer simulations show that the model gives rise simultaneously to several biodiversity patterns in space and time, from species abundance distributions to the waxing and waning of geographic ranges. We find that trophic position in the network plays a crucial role when it comes to the time evolution of range sizes, because the trophic context restricts the occurrence and survival of species especially on higher trophic levels.

ecology↗