Protection from UV light is an evolutionarily conserved feature of the haematopoietic niche

Kapp, Friedrich; Perlin, Julie R.; Hagedorn, Elliott J.; Gansner, John M.; Schwarz, Daniel; O’Connell, Lauren A.; Johnson, Nicholas S.; Amemiya, Chris T.; Fisher, David E.; Wölfle, Ute; Trompouki, Eirini; Niemeyer, Charlotte M.; Driever, Wolfgang; Zon, Leonard I.

doi:10.1038/s41586-018-0213-0

Cited by 63 publications

(60 citation statements)

References 30 publications

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“…Given the pivotal role of stem cells in tissue maintenance and cancer formation, the protection of stem cells from DNA damage appears to be of utmost importance for the evolution of long-lived vertebrate species. One measure of stem cell protection from environmental factors inducing DNA damage certainly is the sheltering in niches [1]. Keeping stem cells in a quiescent state with a slow cell cycle profile and markedly reduced metabolic activity further evolved as a protective mechanism against accumulation of DNA damage (reviewed in ref.…”

Section: Introductionmentioning

confidence: 99%

Elevated Hedgehog activity contributes to attenuated DNA damage responses in aged hematopoietic cells

et al. 2019

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Accumulation of DNA damage and myeloid-skewed differentiation characterize aging of the hematopoietic system, yet underlying mechanisms remain incompletely understood. Here, we show that aging hematopoietic progenitor cells particularly of the myeloid branch exhibit enhanced resistance to bulky DNA lesions-a relevant type of DNA damage induced by toxins such as cancer drugs or endogenous aldehydes. We identified aging-associated activation of the Hedgehog (Hh) pathway to be connected to this phenotype. Inhibition of Hh signaling reverts DNA damage tolerance and DNA damage-resistant proliferation in aged hematopoietic progenitors. Vice versa, elevating Hh activity in young hematopoietic progenitors is sufficient to impair DNA damage responses. Altogether, these findings provide experimental evidence for aging-associated increases in Hh activity driving DNA damage tolerance in myeloid progenitors and myeloid-skewed differentiation. Modulation of Hh activity could thus be explored as a therapeutic strategy to prevent DNA damage tolerance, myeloid skewing, and disease development in the aging hematopoietic system.

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Section: Introductionmentioning

confidence: 99%

Elevated Hedgehog activity contributes to attenuated DNA damage responses in aged hematopoietic cells

et al. 2019

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“… Skin color patterns are ubiquitous in nature, evolve rapidly, and impact social behavior 1 , predator avoidance 2 , and protection from ultraviolet irradiation 3 . A leading model system for vertebrate skin patterning is the zebrafish 4-7 ; its alternating blue stripes and yellow interstripes depend on guanine crystal-containing cells called iridophores that reflect light.…”

mentioning

confidence: 99%

In situdifferentiation of iridophore crystallotypes underlies zebrafish stripe patterning

Gur

Bain

Johnson

et al. 2020

Preprint

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22Skin color patterns are ubiquitous in nature, evolve rapidly, and impact social 23 behavior 1 , predator avoidance 2 , and protection from ultraviolet irradiation 3 . A 24 leading model system for vertebrate skin patterning is the zebrafish 4-7 ; its 25 alternating blue stripes and yellow interstripes depend on guanine crystal-26 containing cells called iridophores that reflect light. It was suggested that the 27 zebrafish's alternating color pattern arises from a single type of iridophore 28 migrating differentially to stripes and interstripes 7-9 . When we tracked iridophores, 29 however, we found they did not migrate between stripes and interstripes but 30 instead differentiated and proliferated in place based on their micro-environment. 31RNA seq analysis further revealed stripe and interstripe iridophores had different 32 transcriptomic states, while cryogenic scanning electron microscopy and micro-33 X-ray diffraction showed they had different guanine crystal organizations and 34 responsiveness to norepinephrine, all indicating that stripe and interstripe 35 iridophores are different cell types. Based on these results, we present a new 36 model of skin patterning in zebrafish in which distinct iridophore crystallotypes 37 containing specialized, physiologically responsive, subcellular organelles arise in 38 stripe and interstripe zones by in situ differentiation. In this model, pattern 39 phenotype depends not only on interactions among pigment cells that affect their 40 arrangements, but also on factors that specify subcellular organization and 41 physiological responsiveness of specialized organelles. 42 43 Introduction 1 Biological patterning is ubiquitous in nature, but mechanisms underlying its 2 establishment and maintenance have been well-documented in only a few instances that 3 are unlikely to represent the full spectrum of pattern-forming systems 6,10 . Indeed, 4 patterning can arise in response to graded positional information or by self-organization 5 of interacting cells, and it can require alternative specification of cell-types from a 6 common progenitor or sorting-out of cells that are heterogeneous already. Elucidating 7 the mechanisms required to pattern cells in diverse tissues and organs is fundamental to 8 understanding development and how phenotypes evolve.9The alternating dark (blue) and light (yellow) pigmented stripe pattern of adult 10 zebrafish Danio rerio (Fig. 1a) is a useful model for dissecting patterning 11 mechanisms 4,5,7,11,12 . Cells within the dark stripes include black pigment-containing 12 melanophores; cells in the light stripes (known as "interstripes") include orange-pigment 13 containing xanthophores; and both dark stripes and light interstripes contain specialized 14 cells called iridophores 13,14 . Iridophores are the major players for skin pattern 15 establishment and reiteration in zebrafish. They behave as reflective cells, exhibiting 16 angular-dependent changes in hue-iridescence-owing to membrane-bound reflecting 17 platelets of crystalline guanine 14-16...

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“…In a study by Kapp et al the HSPC niche in zebrafish was examined on the assumption that niches in terrestrial animals would have evolved at sites protecting the HSPCs from ionizing radiation while the water would have protected aquatic animals. They revealed that melanocytes are forming a protective umbrella over the HSPCs in different species of fish and frogs and by this protects the cells from UV light and its damaging effect on DNA as well as its ability to induce cell death (Kapp et al, 2018). This finding could explain why HSCs are found in the BM of terrestrial animal since the bone creates complete protection from UV irradiation.…”

Section: Bone Marrow Nichesmentioning

confidence: 98%

Hypoxia inducible factor 1 alpha : dependent and independent regulation of hematopoietic stem cells and leukemia

Halvarsson

2018

Linköping University Medical Dissertations

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Protection from UV light is an evolutionarily conserved feature of the haematopoietic niche

Cited by 63 publications

References 30 publications

Elevated Hedgehog activity contributes to attenuated DNA damage responses in aged hematopoietic cells

Elevated Hedgehog activity contributes to attenuated DNA damage responses in aged hematopoietic cells

In situdifferentiation of iridophore crystallotypes underlies zebrafish stripe patterning

Hypoxia inducible factor 1 alpha : dependent and independent regulation of hematopoietic stem cells and leukemia

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