csrnp1a Is Necessary for the Development of Primitive Hematopoiesis Progenitors in Zebrafish

Abstract

The CSRNP (cystein-serine-rich nuclear protein) transcription factors are conserved from Drosophila to human. Functional studies in mice, through knockout for each of their paralogs, have resulted insufficient to elucidate the function of this family of proteins in vertebrate development. Previously, we described the function of the zebrafish ortholog, Csnrp1/Axud1, showing its essential role in the survival and proliferation of cephalic progenitors. To extend our understanding of this family, we have studied the function of its paralog csrnp1a. Our results show that csrnp1a is expressed from 0 hpf, until larval stages, particularly in cephalic territories and in the intermediate cell mass (ICM). Using morpholinos in wild type and transgenic lines we observed that Csrnp1a knockdown generates a mild reduction in head size and a depletion of blood cells in circulation. This was combined with in situ hybridizations to analyze the expression of different mesodermal and primitive hematopoiesis markers. Morphant embryos have impaired blood formation without disruption of mesoderm specification, angiogenesis or heart development. The reduction of circulating blood cells occurs at the hematopoietic progenitor level, affecting both the erythroid and myeloid lineages. In addition, cell proliferation was also altered in hematopoietic anterior sites, specifically in spi1 expression domain. These and previous observations suggest an important role of Csnrps transcription factors in progenitor biology, both in the neural and hematopoietic linages.

Transcriptome sequencing supports a conservation of macrophage polarization in fish

“…In human M2 macrophages dependent on the study 1 , 64 19.9 445.2 agrn Agrin 00029572 4.3 Extracellular-matrix protein involved in monocyte/macrophage survival, cytoskeleton formation and phagocytosis 28 11.2 153.8 pde4bb Phosphodiësterase 4b 00024882 00020192 4.3 3.6 Degrades second messenger cAMP, promoting pro- and regulating anti-inflammatory effects 65 - 67 17.4 25.4 284.8 266.8 vegfaa Vascular endothelial growth factor Aa 00013154 4.3 Signaling protein involved in angiogenesis and tissue generation. Upregulated in M2 macrophages 68 , 69 4.9 77.9 csrnp1a Cysteine-serine-rich nuclear protein 1a 00015701 4.2 Transcriptional activator involved in Wnt-signaling and involved in primitive hematopoiesis in zebrafish 70 . Upregulated in macrophages of different origins with multiple stimuli including murine BMDM with Il-13 71 or LPS 72 7.5 117.1 il1β Interleukin 1 beta 00043439 00043440 4.2 4.0 Pro-inflammatory cytokine.…”

“…Data are of n = 3 fish. 1 Mills et al, 2000, 28 Mazzon et al, 2012, 52 Chen et al, 2001, 53 Chen and Lau, 2009, 54 Orecchioni et al, 2019, 55 Martinez and Gordon, 2014, 56 Nadella et al, 2015, 57 Sun and Kaartinen., 2018, 58 McLatchie et al, 1998, 59 Chen et al, 2011, 60 Pang et al, 2013, 61 Rogers et al, 2017, 62 Chen et al, 2019, 63 Broz et al, 2019, 64 Munder et al, 1999, 65 Jin et al, 2005, 66 Hertz et al, 2009, 67 Yang et al, 2017, 68 Stockmann et al, 2011, 69 Roszer et al, 2015, 70 Espina et al, 2013, 71 Das et al, 2018, 72 Eichelbaum and Krijgsveld, 2014, 26 Mantovani et al, 2019, 73 Shirakata et al, 2005, 74 Edwards et al, 2009, 75 Oteng et al, 2019, 76 Feingold et al, 2009, 77 Cho et al, 2019, 27 Scarl et al, 2017, 78 Wary and Humtsoe 2005, 79 Gustafsson et al, 2008, 80 Panchatcharam et al, 2014, 40 Carmans et al, 2010, 41 Loomis et al, 2019, 81 Della Fazia et al, 1997, 51 Ahmed and Prigent, 2017.…”

“…Data are of n = 3 fish. 1 Mills et al, 2000, 28 Mazzon et al, 2012, 52 Chen et al, 2001, 53 Chen and Lau, 2009, 54 Orecchioni et al, 2019, 55 Martinez and Gordon, 2014, 56 Nadella et al, 2015, 57 Sun and Kaartinen., 2018, 58 McLatchie et al, 1998, 59 Chen et al, 2011, 60 Pang et al, 2013, 61 Rogers et al, 2017, 62 Chen et al, 2019, 63 Broz et al, 2019, 64 Munder et al, 1999, 65 Jin et al, 2005, 66 Hertz et al, 2009, 67 Yang et al, 2017, 68 Stockmann et al, 2011, 69 Roszer et al, 2015, 70 Espina et al, 2013, 71 Das et al, 2018, 72 Eichelbaum and Krijgsveld, 2014, Panchatcharam et al, 2014, 40 Carmans et al, 2010, 41 Loomis et al, 2019, 81 Della Fazia et al, 1997, 51 Ahmed and Prigent, 2017. www.nature.com/scientificreports/ increase in il1β, nos2b and saa expression in M1 but not in M2 macrophages (Fig. 3b-d).…”

Meta-analysis of genome-wide association studies discovers multiple loci for chronic lymphocytic leukemia

“…The 3p22.2 SNP (rs1274963) is an intronic variant in the gene CSRNP1 (cysteine-serine-rich nuclear protein 1), which is induced by AXIN1, a scaffold protein that is a negative regulator of the Wnt/signalling pathway 30 . A putative tumour suppressor with potential apoptosis activity 31 , CSRNP1 plays an important role in the development of haematopoiesis progenitors in zebrafish 32 and has been shown to be expressed in many tissues, with leukocytes being among those with the highest abundance 30 . The SNP resides in an area with strong regulatory potential based on histone marks, DNaseI hypersensitivity and transcription factor binding sites ( Supplementary Table 8 ) and is located within a strong enhancer in the lymphoblastoid cell line, GM12878 ( Supplementary Fig.…”

The CSRNP Gene Family Serves as a Prognostic Biomarker in Clear Cell Renal Cell Carcinoma

“…The cysteine-serine-rich nuclear protein (CSRNP) family members, CSRNP1, CSRNP2, and CSRNP3, have been considered as nuclear proteins ( 6 ). Their corresponding transcription factors, which are conserved from Drosophila to humans ( 7 ), play essential roles in many important processes, such as cephalic neural progenitor proliferation, overall zebrafish survival ( 8 ), and mouse development ( 6 ).…”