Erythroid‐extrinsic regulation of normal erythropoiesis by retinoic acid receptors

Dewamitta, Sita R.; Joseph, Chacko; Purton, Louise E.; Walkley, Carl R.

doi:10.1111/bjh.12578

Cited by 17 publications

(20 citation statements)

References 17 publications

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“…These targets include genes involved in migration and differentiation of the neural crest-derived periocular mesenchyme and its derivatives [ 46 , 47 ], already known to be regulated by RA. Genes expressed in vascular and hematopoietic lineages ( epo , angptl5 ) are known to be regulated by RA in other organs [ 87 , 88 ], and lens crystallins (though not the specific crystalline genes detected in the present microarray) have been demonstrated as targets of RA signaling [ 89 ].…”

Section: Discussionmentioning

confidence: 99%

Retinoic Acid Signaling Regulates Differential Expression of the Tandemly-Duplicated Long Wavelength-Sensitive Cone Opsin Genes in Zebrafish

et al. 2015

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The signaling molecule retinoic acid (RA) regulates rod and cone photoreceptor fate, differentiation, and survival. Here we elucidate the role of RA in differential regulation of the tandemly-duplicated long wavelength-sensitive (LWS) cone opsin genes. Zebrafish embryos were treated with RA from 48 hours post-fertilization (hpf) to 75 hpf, and RNA was isolated from eyes for microarray analysis. ~170 genes showed significantly altered expression, including several transcription factors and components of cellular signaling pathways. Of interest, the LWS1 opsin gene was strongly upregulated by RA. LWS1 is the upstream member of the tandemly duplicated LWS opsin array and is normally not expressed embryonically. Embryos treated with RA 48 hpf to 100 hpf or beyond showed significant reductions in LWS2-expressing cones in favor of LWS1-expressing cones. The LWS reporter line, LWS-PAC(H) provided evidence that individual LWS cones switched from LWS2 to LWS1 expression in response to RA. The RA signaling reporter line, RARE:YFP indicated that increased RA signaling in cones was associated with this opsin switch, and experimental reduction of RA signaling in larvae at the normal time of onset of LWS1 expression significantly inhibited LWS1 expression. A role for endogenous RA signaling in regulating differential expression of the LWS genes in postmitotic cones was further supported by the presence of an RA signaling domain in ventral retina of juvenile zebrafish that coincided with a ventral zone of LWS1 expression. This is the first evidence that an extracellular signal may regulate differential expression of opsin genes in a tandemly duplicated array.

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Section: Discussionmentioning

confidence: 99%

Retinoic Acid Signaling Regulates Differential Expression of the Tandemly-Duplicated Long Wavelength-Sensitive Cone Opsin Genes in Zebrafish

et al. 2015

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Section: Vitamin A/retinoic Acid In Adult Hematopoiesismentioning

confidence: 99%

“…RARγ -/- mice are anemic [ 56 ] and develop myeloproliferative syndrome, likely by a defective function of RARγ in the bone marrow cellular niche [ 57 ]. The erythropoiesis is normal after conditional deletion of RARα and RARγ in adult cells expressing the EPO receptor (EPOR), indicating that RARγ is playing a function in cells other than erythroid progenitors [ 56 ]. NOTCH and HOXB4 are known regulators of HSC self-renewal [ 58 , 59 ]; while HOXB4 expression in HSC is normal in the RARγ mutants, NOTCH1 and its effector HES1 are both downregulated [ 54 ].…”

Section: Vitamin A/retinoic Acid In Adult Hematopoiesismentioning

confidence: 99%

Role of Vitamin A/Retinoic Acid in Regulation of Embryonic and Adult Hematopoiesis

et al. 2017

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Vitamin A is an essential micronutrient throughout life. Its physiologically active metabolite retinoic acid (RA), acting through nuclear retinoic acid receptors (RARs), is a potent regulator of patterning during embryonic development, as well as being necessary for adult tissue homeostasis. Vitamin A deficiency during pregnancy increases risk of maternal night blindness and anemia and may be a cause of congenital malformations. Childhood Vitamin A deficiency can cause xerophthalmia, lower resistance to infection and increased risk of mortality. RA signaling appears to be essential for expression of genes involved in developmental hematopoiesis, regulating the endothelial/blood cells balance in the yolk sac, promoting the hemogenic program in the aorta-gonad-mesonephros area and stimulating eryrthropoiesis in fetal liver by activating the expression of erythropoietin. In adults, RA signaling regulates differentiation of granulocytes and enhances erythropoiesis. Vitamin A may facilitate iron absorption and metabolism to prevent anemia and plays a key role in mucosal immune responses, modulating the function of regulatory T cells. Furthermore, defective RA/RARα signaling is involved in the pathogenesis of acute promyelocytic leukemia due to a failure in differentiation of promyelocytes. This review focuses on the different roles played by vitamin A/RA signaling in physiological and pathological mouse hematopoiesis duddurring both, embryonic and adult life, and the consequences of vitamin A deficiency for the blood system.

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“…In addition to lower bone mass, Rarg –/– mice developed a myeloproliferative‐like syndrome (MPS) characterized by significantly more granulocytes in the peripheral blood (PB), BM, and spleen . Rarg –/– mice also exhibited defects in erythropoiesis and B lymphopoiesis, with lower numbers of pro‐B and pre‐B lymphocytes in the BM . When BM from wild‐type mice was transplanted into mice with a Rarg –/– microenvironment, the transplanted mice rapidly developed MPS‐like disease and erythrocyte and B lymphocyte defects.…”

Section: Introductionmentioning

confidence: 99%

Retinoic Acid Receptor γ Activity in Mesenchymal Stem Cells Regulates Endochondral Bone, Angiogenesis, and B Lymphopoiesis

Green

Rudolph-Stringer

Straszkowski

et al. 2018

Journal of Bone and Mineral Research

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Retinoic acid receptor (RAR) signaling regulates bone structure and hematopoiesis through intrinsic and extrinsic mechanisms. This study aimed to establish how early in the osteoblast lineage loss of RARγ (Rarg) disrupts the bone marrow microenvironment. Bone structure was analyzed by micro-computed tomography (μCT) in Rarg mice and mice with Rarg conditional deletion in Osterix-Cre-targeted osteoblast progenitors or Prrx1-Cre-targeted mesenchymal stem cells. Rarg tibias exhibited less trabecular and cortical bone and impaired longitudinal and radial growth. The trabecular bone and longitudinal, but not radial, growth defects were recapitulated in Prrx1:Rarg mice but not Osx1:Rarg mice. Although both male and female Prrx1:Rarg mice had low trabecular bone mass, males exhibited increased numbers of trabecular osteoclasts and Prrx1:Rarg females had impaired mineral deposition. Both male and female Prrx1:Rarg growth plates were narrower than controls and their epiphyses contained hypertrophic chondrocyte islands. Flow cytometry revealed that male Prrx1:Rarg bone marrow exhibited elevated pro-B and pre-B lymphocyte numbers, accompanied by increased Cxcl12 expression in bone marrow cells. Prrx1:Rarg bone marrow also had elevated megakaryocyte-derived Vegfa expression accompanied by smaller sinusoidal vessels. Thus, RARγ expression by Prrx1-Cre-targeted cells directly regulates endochondral bone formation and indirectly regulates tibial vascularization. Furthermore, RARγ expression by Prrx1-Cre-targeted cells extrinsically regulates osteoclastogenesis and B lymphopoiesis in male mice. © 2018 American Society for Bone and Mineral Research.

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Erythroid‐extrinsic regulation of normal erythropoiesis by retinoic acid receptors

Cited by 17 publications

References 17 publications

Retinoic Acid Signaling Regulates Differential Expression of the Tandemly-Duplicated Long Wavelength-Sensitive Cone Opsin Genes in Zebrafish

Retinoic Acid Signaling Regulates Differential Expression of the Tandemly-Duplicated Long Wavelength-Sensitive Cone Opsin Genes in Zebrafish

Role of Vitamin A/Retinoic Acid in Regulation of Embryonic and Adult Hematopoiesis

Retinoic Acid Receptor γ Activity in Mesenchymal Stem Cells Regulates Endochondral Bone, Angiogenesis, and B Lymphopoiesis

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