Regulation of erythropoiesis in the spleen by Desert Hedgehog (Dhh)
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA843316 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR19435677_1.fastq.gz | Fastqsanger.gz | |||
| SRR19435677_2.fastq.gz | Fastqsanger.gz | |||
| SRR19435678_1.fastq.gz | Fastqsanger.gz | |||
| SRR19435678_2.fastq.gz | Fastqsanger.gz | |||
| SRR19435679_1.fastq.gz | Fastqsanger.gz |
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Project description:Dhh negatively regulates multiple stages of erythrocyte differentiation. In Dhh-deficient bone marrow, the common myeloid progenitor (CMP) population was increased, but differentiation from CMP to granulocyte/macrophage progenitor was decreased, and the mature granulocyte population was decreased, compared with wild-type (WT). In contrast, differentiation from CMP to megakaryocyte/erythrocyte progenitor was increased, and the megakaryocyte/erythrocyte progenitor population was increased. In Dhh-deficient spleen and bone marrow, BFU-Es and erythroblast populations were increased compared with WT. During recovery of hematopoiesis after irradiation, and under conditions of stress-induced erythropoiesis, erythrocyte differentiation was accelerated in both spleen and bone marrow of Dhh-deficient mice compared with WT. To investigate possible mechanisms for its regulation of erythropoiesis we carried out RNAsequencing on Facs-sorted erythroblast population II (CD71+Ter119+) cells from Dhh-/-, Dhh+/- and WR mice.
2022-05-31 | GSE205034 | GEO
Project description:Glioblastoma is the most frequent type of adult-onset malignant brain tumors and has a very poor prognosis. A cell population called glioblastoma stem cells has been shown to be one of the mechanisms by which glioblastoma acquires therapy resistance. Therefore, there is a need to establish novel therapeutic strategies useful for inhibiting the cell population. γ-glutamylcyclotransferase (GGCT) is an enzyme involved in the synthesis and metabolism of glutathione, which is highly expressed in a wide range of cancer types including glioblastoma, and inhibition of its expression has been reported to have antitumor effects on various cancer types. In this study, we searched for pathways affected by the growth-promoting effect of GGCT overexpression in mouse embryonic fibroblasts NIH3T3 by comprehensive gene expression analysis and found the hedgehog pathway. Knockdown of GGCT inhibited proliferation of glioblastoma stem cells derived from a mouse glioblastoma model and caused decreased expression of desert hedgehog (Dhh), a representative ligand of the pathway, and the downstream target Gli1. To analyze the contribution of reduced Dhh, we activated the hedgehog pathway by forced expression of Dhh. We found that Dhh overexpression significantly restored the growth suppressive effect of GGCT knockdown. The results of this study indicate that high GGCT expression is important for Dhh expression and activation of the hedgehog pathway, which is required to maintain glioblastoma stem cell proliferation. Therefore, inhibition of GGCT function may be useful in suppressing stemness of glioblastoma stem cells accompanied with activation of the hedgehog pathway.
2024-05-20 | GSE266154 | GEO
Project description:Physiologically, trophoblast progenitor cells differentiate into placental villous cytotrophoblast cells (CTBs). CTBs either differentiate into invasive lineage to yields extravillous cytotrophoblast cells (EVTs), or undergo cell fusion lineage to yields syncytiotrophoblast cells (STBs)，Sonic hedgehog (Shh) together with indian hedgehog (Ihh) and desert hedgehog (Dhh) consist of ligand of hedgehog signaling pathway, which plays pivotal roles in regulating cell proliferation, cell differentiation, organogenesis and development, even involving in tumorigenesis and progression. previous study had summarized and indicatedthat hedgehog proteins played important roles in regulating hematopoiesis, vasculogenesis and angiogenesis during embryogenesis and development. Herein, we investigate the effect of the Sonic Hedgehog morphogen inhibitor Cyclopamine on JAR cells
2019-12-31 | GSE130367 | GEO
Project description:The goal of the microarray analysis is to determine the redundant and distinct roles of Dhh and Ihh in ovarian functions
2018-05-30 | GSE109842 | GEO
Project description:Although testosterone deficiency (TD) may be present in 1 out of 5 men 40 years or older, the factors responsible for TD remain largely unknown. Leydig stem cells (LSCs) differentiate into adult Leydig cells (ALC) and produce testosterone in the testes under the pulsatile control of luteinizing hormone (LH) from the pituitary gland. However, recent studies have suggested that the testicular microenvironment (TME), which is comprised of Sertoli and peritubular myoid cells (PMC), plays an instrumental role in LSC differentiation and testosterone production under the regulation of the desert hedgehog signaling pathway (DHH). It was hypothesized that TME releases paracrine factors to modulate LSC differentiation. For this purpose, cells (Sertoli, PMCs, LSCs and ALCs) were extracted from men undergoing testis biopsies for sperm retrieval and were evaluated for the paracrine factors in the presence or absence of TME (Sertoli and PMC). The results demonstrated that TME secretes leptin which induces LSC differentiation and increases T production. Leptin’s effects on LSC differentiation and T production, however, are inversely concentration-dependent: positive at low doses and negative at higher doses. Mechanistically, leptin acts on LSCs upstream of DHH; leptin-DHH regulation functions unidirectionally insofar as DHH gain or loss of function has no effects on leptin levels. Taken together, these findings identify leptin as a key paracrine factor released by cells within the TME that modulates LSC differentiation and testosterone release from mature Leydig cells, a finding with important clinical implications for TD.
2022-02-17 | GSE196702 | GEO
Project description:Extramedullary erythropoiesis is not expected in healthy adult mice, but erythropoietic gene expression was elevated in lineage-depleted spleen cells from cd47−/− mice. Elevated expression of several genes associated with early stages of erythropoiesis was observed in mice lacking CD47 or its signaling ligand thrombospondin-1, consistent with previous evidence that this signaling pathway inhibits expression of multipotent stem cell transcription factors in spleen. In contrast, cells expressing markers of committed erythroid progenitors including erythropoietin receptor, aquaporin-1, glycophorin A, and erythrocyte membrane-associated protein were more abundant in cd47−/− spleens but significantly depleted in thbs1−/− spleens. Single cell transcriptome analysis indicated that loss of CD47 is associated with accumulation and increased proliferation of CD34− committed erythroid progenitors in spleen, consistent with the known function of CD47 to limit turnover of aging erythrocytes. Conversely, loss of thrombospondin-1 delays turnover, which suppresses erythropoiesis in thbs1−/− spleens relative to the basal level in wild type mice.
2024-06-17 | GSE239427 | GEO
Project description:Extramedullary erythropoiesis is not expected in healthy adult mice, but erythropoietic gene expression was elevated in lineage-depleted spleen cells from cd47−/− mice. Elevated expression of several genes associated with early stages of erythropoiesis was observed in mice lacking CD47 or its signaling ligand thrombospondin-1, consistent with previous evidence that this signaling pathway inhibits expression of multipotent stem cell transcription factors in spleen. In contrast, cells expressing markers of committed erythroid progenitors including erythropoietin receptor, aquaporin-1, glycophorin A, and erythrocyte membrane-associated protein were more abundant in cd47−/− spleens but significantly depleted in thbs1−/− spleens. Single cell transcriptome analysis indicated that loss of CD47 is associated with accumulation and increased proliferation of CD34− committed erythroid progenitors in spleen, consistent with the known function of CD47 to limit turnover of aging erythrocytes. Conversely, loss of thrombospondin-1 delays turnover, which suppresses erythropoiesis in thbs1−/− spleens relative to the basal level in wild type mice.
2024-06-17 | GSE239424 | GEO
Project description:Transcriptomes comparisons of Dhh KO, Ihh KO and Dhh/Ihh DKO ovaries
| PRJNA432169 | ENA
Project description:Background46,XY disorders of sex development (DSD) comprise a heterogeneous group of congenital conditions. Mutations in a variety of genes can affect gonadal development or androgen biosynthesis/action and thereby influence the development of the internal and external genital organs.ObjectiveThe objective of the study was to identify the genetic cause in two 46,XY sisters of a consanguineous family with DSD and gonadal tumor formation.MethodsWe used a next-generation sequencing approach by exome sequencing. Electrophysiological and high-resolution ultrasound examination of peripheral nerves as well as histopathological examination of the gonads were performed.ResultsWe identified a novel homozygous R124Q mutation in the desert hedgehog gene (DHH), which alters a conserved residue among the three mammalian Hedgehog ligands sonic hedgehog, Indian hedgehog, and desert hedgehog. No other relevant mutations in DSD-related genes were encountered. The gonads of one patient showed partial gonadal dysgenesis with loss of Leydig cells in tubular areas with seminoma in situ and a hyperplasia of Leydig cell-like cells expressing CYP17A1 in more dysgenetic parts of the gonad. In addition, both patients suffer from a polyneuropathy. High-resolution ultrasound revealed a structural change of peripheral nerve structure that fits well to a minifascicle formation of peripheral nerves.ConclusionMutations in DHH play a role in 46,XY gonadal dysgenesis and are associated with seminoma formation and a neuropathy with minifascicle formation. Gonadal dysgenesis in these cases may be due to impairment of Sertoli cell-Leydig cell interaction during gonadal development.
| S-EPMC4490300 | biostudies-literature
Project description:Hox genes are required for the development of the intestinal caecum, a major organ of species eating plants. We have analysed the transcriptional regulation of Hoxd genes in caecal buds and show that they are controlled by a series of enhancers located in a gene desert telomeric to the HoxD cluster. The start site of two neighboring and opposite long non-coding RNAs, Hotdog and Twin of Hotdog, specifically transcribed in the caecum, contacts the expressed Hoxd genes in the framework of a topological domain, a large domain of interactions, which ensures a robust transcription of these genes during caecum budding. We show that hedgehogs have kept this regulatory potential despite the absence of caecum, suggesting that these enhancers are used in other developmental situations. In this context, we discuss some striking similarities between the caecum and the limb buds, suggesting the implementation of a common budding tool-kit. Transcriptional activity at the HoxD locus in the hedgehog developing gut at E13.5, Differential gene expression analysis along the hedgehog developing gut
2013-10-23 | E-GEOD-44696 | biostudies-arrayexpress