LINGO3 regulates mucosal tissue regeneration and promotes TFF2 dependent recovery from colitis

Zullo, Kelly; Douglas, Bonnie; Maloney, Nicole M; Ji, Yingbiao; Wei, Yun; Herbine, Karl; Cohen, Richard L.; Pastore, Christopher; Cramer, Zvi; Wang, Xin; Wei, Wenjie; Somsouk, Ma; Hung, Li-Yin; Lengner, Christopher J.; Kohanski, Michael H; Cohen, Noam A.; Herbert, De’Broski R.

doi:10.1080/00365521.2021.1917650

Cited by 9 publications

(6 citation statements)

References 65 publications

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“…The TSA administration in the right gonad stimulated the chicken Zar1 transcription to even exceed the expression level of the left gonad. Similarly, the expression level of other reproductive and developmental genes, such as Lingo3 [ 49 ], Scnn1g [ 50 ], Tfcp2l1 [ 51 ], were all elevated to the comparable levels of the developing left gonad (Fig. 7 A).…”

Section: Resultsmentioning

confidence: 97%

H3K27ac chromatin acetylation and gene expression analysis reveal sex- and situs-related differences in developing chicken gonads

et al. 2022

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Background Birds exhibit a unique asymmetry in terms of gonad development. The female left gonad generates a functional ovary, whereas the right gonad regresses. In males, both left and right gonads would develop into testes. How is this left/right asymmetry established only in females but not in males remains unknown. The epigenetic regulation of gonadal developmental genes may contribute to this sex disparity. The modification of histone tails such as H3K27ac is tightly coupled to chromatin activation and gene expression. To explore whether H3K27ac marked chromatin activation is involved in the asymmetric development of avian gonads, we probed genome-wide H3K27ac occupancy in left and right gonads from both sexes and related chromatin activity profile to the expression of gonadal genes. Furthermore, we validated the effect of chromatin activity on asymmetric gonadal development by manipulating the chromatin histone acetylation levels. Methods The undifferentiated gonads from both sides of each sex were collected and subjected to RNA-Seq and H3K27ac ChIP-Seq experiments. Integrated analysis of gene expression and active chromatin regions were performed to identify the sex- and situs-specific regulation and expression of gonadal genes. The histone deacetylase inhibitor trichostatin A (TSA) was applied to the undifferentiated female right gonads to assess the effect of chromatin activation on gonadal gene expression and cell proliferation. Results Even before sex differentiation, the gonads already show divergent gene expression between different sexes and between left/right sides in females. The sex-specific H3K27ac chromatin distributions coincide with the higher expression of male/female specification genes in each sex. Unexpectedly, the H3K27ac marked chromatin activation show a dramatic difference between left and right gonads in both sexes, although the left/right asymmetric gonadal development was observed only in females but not in males. In females, the side-specific H3K27ac occupancy instructs the differential expression of developmental genes between the pair of gonads and contributes to the development of left but not right gonad. However, in males, the left/right discrepancy of H3K27ac chromatin distribution does not drive the side-biased gene expression or gonad development. The TSA-induced retention of chromatin acetylation causes up-regulation of ovarian developmental genes and increases cell proliferation in the female right gonad. Conclusions We revealed that left/right asymmetry in H3K27ac marked chromatin activation exists in both sexes, but this discrepancy gives rise to asymmetric gonadal development only in females. Other mechanisms overriding the chromatin activation would control the symmetric development of male gonads in chicken.

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Section: Resultsmentioning

confidence: 97%

H3K27ac chromatin acetylation and gene expression analysis reveal sex- and situs-related differences in developing chicken gonads

et al. 2022

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“…A total of 5,123 genes ( P-adj < 0.1) were differentially expressed in sham-fumigated nestlings across the urban (up-regulated) and non-urban (down-regulated) sites - of which, 2,521 were up-regulated and 2,602 were down-regulated. Altogether, 57 genes demonstrated strong expression patterns (± 4-fold change), including frizzled class receptor 10 FZD10 (16.20-fold change), a primary receptor for Wnt signaling, leucine rich repeat and Ig domain containing 3 LINGO3 (5.35-fold change), which has been shown to regulate mucosal tissue regeneration in humans and promote wound healing, adenosine deaminase ADA (-8.17-fold change), associated with hemolytic anemia, and hepatic leukemia factor HLF (-5.64-fold change), known to influence the renewal of hematopoietic stem cells (Wang et al, 2016; Zullo et al, 2021; Chen & Mitchell, 1994; Komorowska et al, 2017). In fumigated nestlings, only two genes were up-regulated in the urban site, bisphosphoglycerate mutase BPGM (3.23-fold change), a regulator of erythrocyte metabolism and hemoglobin in red blood cells, and zinc finger protein GLIS1 (3.40-fold change), which has been significantly associated with bill length (Xu et al, 2020; Lundregan et al, 2018).…”

Section: Resultsmentioning

confidence: 99%

Urban living can rescue Darwin’s finches from the lethal effects of invasive vampire flies

Knutie

Webster

Vaziri

et al. 2023

Preprint

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Human activity changes multiple factors in the environment, which can have additive or neutralizing effects on organisms. However, few studies have explored the causal effects of multiple anthropogenic factors, such as urbanization and invasive species, on animals, and the mechanisms that mediate these interactions. This study examines the influence of urbanization on the detrimental effect of invasive avian vampire flies (Philornis downsi) on endemic Darwin's finches in the Galapagos Islands. We experimentally manipulated nest fly abundance in an urban and non-urban area and then characterized nestling health, survival, diet, and gene expression patterns related to host defense. Survival of non-parasitized nestlings from urban (85%) and non-urban (78%) nests did not differ significantly. However, parasitized, non-urban nestlings lost more blood and had lower survival (7%) compared to urban nestlings (50%). Stable isotopic values (δ15N) from nestling feces revealed that diet differed between urban and non-urban nestlings. δ15N values correlated negatively with parasite abundance, which suggests that diet might influence host defenses (e.g., tolerance and resistance). Parasitized urban nestlings differentially expressed genes within pathways associated with red blood cell production (tolerance) and pro-inflammatory response (innate immunological resistance), compared to parasitized non-urban nestlings. In contrast, parasitized non-urban nestlings differentially expressed genes within pathways associated with immunoglobulin production (adaptive immunological resistance). Our results suggest that urban nestlings are investing more in pro-inflammatory responses to resist parasites, but also recovering more blood cells to tolerate blood loss. Although non-urban nestlings are mounting an adaptive immune response, it is likely a last effort by the immune system rather than an effective defense against avian vampire flies since few nestlings survived.

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“…A pairwise differential expression analysis observing two locations (urban and non-urban) and two treatments (fumigated and sham-fumigated), with an interaction, was conducted (File S1). A with hemolytic anemia, and hepatic leukemia factor HLF (−5.64-fold change), known to influence the renewal of hematopoietic stem cells (Chen & Mitchell, 1994;Komorowska et al, 2017;Wang et al, 2016;Zullo et al, 2021). In fumigated nestlings, only two genes were upregulated in the urban location: bisphosphoglycerate mutase BPGM (+3.24-fold change), a regulator of erythrocyte metabolism and hemoglobin in red blood cells, and zinc finger protein GLIS1 (+3.40fold change), which has been significantly associated with bill length (Lundregan et al, 2018;Xu et al, 2020).…”

Section: Differentially Expressed Genesmentioning

confidence: 99%

Urban living can rescue Darwin's finches from the lethal effects of invasive vampire flies

Knutie,

Webster,

Vaziri

et al. 2024

Global Change Biology

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Human activity changes multiple factors in the environment, which can have positive or negative synergistic effects on organisms. However, few studies have explored the causal effects of multiple anthropogenic factors, such as urbanization and invasive species, on animals and the mechanisms that mediate these interactions. This study examines the influence of urbanization on the detrimental effect of invasive avian vampire flies (Philornis downsi) on endemic Darwin's finches in the Galápagos Islands. We experimentally manipulated nest fly abundance in urban and non‐urban locations and then characterized nestling health, fledging success, diet, and gene expression patterns related to host defense. Fledging success of non‐parasitized nestlings from urban (79%) and non‐urban (75%) nests did not differ significantly. However, parasitized, non‐urban nestlings lost more blood, and fewer nestlings survived (8%) compared to urban nestlings (50%). Stable isotopic values (δ15N) from urban nestling feces were higher than those from non‐urban nestlings, suggesting that urban nestlings are consuming more protein. δ15N values correlated negatively with parasite abundance, which suggests that diet might influence host defenses (e.g., tolerance and resistance). Parasitized, urban nestlings differentially expressed genes within pathways associated with red blood cell production (tolerance) and pro‐inflammatory response (innate immunological resistance), compared to parasitized, non‐urban nestlings. In contrast, parasitized non‐urban nestlings differentially expressed genes within pathways associated with immunoglobulin production (adaptive immunological resistance). Our results suggest that urban nestlings are investing more in pro‐inflammatory responses to resist parasites but also recovering more blood cells to tolerate blood loss. Although non‐urban nestlings are mounting an adaptive immune response, it is likely a last effort by the immune system rather than an effective defense against avian vampire flies since few nestlings survived.

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LINGO3 regulates mucosal tissue regeneration and promotes TFF2 dependent recovery from colitis

Cited by 9 publications

References 65 publications

H3K27ac chromatin acetylation and gene expression analysis reveal sex- and situs-related differences in developing chicken gonads

H3K27ac chromatin acetylation and gene expression analysis reveal sex- and situs-related differences in developing chicken gonads

Urban living can rescue Darwin’s finches from the lethal effects of invasive vampire flies

Urban living can rescue Darwin's finches from the lethal effects of invasive vampire flies

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