Cargando…

The Lysine Methyltransferase SMYD2 Is Required for Definite Hematopoietic Stem Cell Production in the Mouse Embryo

The five-membered SET and MYND domain-containing lysine methyltransferase (SMYD) family plays pivotal roles in development and differentiation. Initially characterized within the cardiovascular system, one such member, SMYD2, has been implicated in transcriptional and apoptotic regulation of hematop...

Descripción completa

Detalles Bibliográficos
Autores principales: Edwards, Melissa A., Brown, Mark A., Alshiraihi, Ilham, Jarrell, Dillon K., Tucker, Haley O.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7560092/
https://www.ncbi.nlm.nih.gov/pubmed/32722433
http://dx.doi.org/10.3390/vetsci7030100
_version_ 1783595010095054848
author Edwards, Melissa A.
Brown, Mark A.
Alshiraihi, Ilham
Jarrell, Dillon K.
Tucker, Haley O.
author_facet Edwards, Melissa A.
Brown, Mark A.
Alshiraihi, Ilham
Jarrell, Dillon K.
Tucker, Haley O.
author_sort Edwards, Melissa A.
collection PubMed
description The five-membered SET and MYND domain-containing lysine methyltransferase (SMYD) family plays pivotal roles in development and differentiation. Initially characterized within the cardiovascular system, one such member, SMYD2, has been implicated in transcriptional and apoptotic regulation of hematopoiesis. Deletion of Smyd2 in adult mouse Hemaopoietic Stem Cells (HSC) using an interferon-inducible mx1-Cre-mediated conditional knockout (CKO) led to HSC reduction via both apoptosis and transcriptional deficiencies. Since HSC are specified from hemogenic endothelial (HE) cells in the dorsal aorta (DA), we sought to determine whether the flaw in HSC originated embryologically from this site. Toward this end, we performed deletion with vav-Cre mice, which is active in all hematopoietic and endothelial tissues from E10.5 embryonic life onward. Unexpectedly, we observed no defects in the embryo, other than apoptotic loss of definite HSC, whereas adult hematopoietic populations downstream were unaffected. These results further establish the importance of SMYD2 in antiapoptotic gene control of gene expression from the embryo to the adult.
format Online
Article
Text
id pubmed-7560092
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-75600922020-10-22 The Lysine Methyltransferase SMYD2 Is Required for Definite Hematopoietic Stem Cell Production in the Mouse Embryo Edwards, Melissa A. Brown, Mark A. Alshiraihi, Ilham Jarrell, Dillon K. Tucker, Haley O. Vet Sci Article The five-membered SET and MYND domain-containing lysine methyltransferase (SMYD) family plays pivotal roles in development and differentiation. Initially characterized within the cardiovascular system, one such member, SMYD2, has been implicated in transcriptional and apoptotic regulation of hematopoiesis. Deletion of Smyd2 in adult mouse Hemaopoietic Stem Cells (HSC) using an interferon-inducible mx1-Cre-mediated conditional knockout (CKO) led to HSC reduction via both apoptosis and transcriptional deficiencies. Since HSC are specified from hemogenic endothelial (HE) cells in the dorsal aorta (DA), we sought to determine whether the flaw in HSC originated embryologically from this site. Toward this end, we performed deletion with vav-Cre mice, which is active in all hematopoietic and endothelial tissues from E10.5 embryonic life onward. Unexpectedly, we observed no defects in the embryo, other than apoptotic loss of definite HSC, whereas adult hematopoietic populations downstream were unaffected. These results further establish the importance of SMYD2 in antiapoptotic gene control of gene expression from the embryo to the adult. MDPI 2020-07-25 /pmc/articles/PMC7560092/ /pubmed/32722433 http://dx.doi.org/10.3390/vetsci7030100 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Edwards, Melissa A.
Brown, Mark A.
Alshiraihi, Ilham
Jarrell, Dillon K.
Tucker, Haley O.
The Lysine Methyltransferase SMYD2 Is Required for Definite Hematopoietic Stem Cell Production in the Mouse Embryo
title The Lysine Methyltransferase SMYD2 Is Required for Definite Hematopoietic Stem Cell Production in the Mouse Embryo
title_full The Lysine Methyltransferase SMYD2 Is Required for Definite Hematopoietic Stem Cell Production in the Mouse Embryo
title_fullStr The Lysine Methyltransferase SMYD2 Is Required for Definite Hematopoietic Stem Cell Production in the Mouse Embryo
title_full_unstemmed The Lysine Methyltransferase SMYD2 Is Required for Definite Hematopoietic Stem Cell Production in the Mouse Embryo
title_short The Lysine Methyltransferase SMYD2 Is Required for Definite Hematopoietic Stem Cell Production in the Mouse Embryo
title_sort lysine methyltransferase smyd2 is required for definite hematopoietic stem cell production in the mouse embryo
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7560092/
https://www.ncbi.nlm.nih.gov/pubmed/32722433
http://dx.doi.org/10.3390/vetsci7030100
work_keys_str_mv AT edwardsmelissaa thelysinemethyltransferasesmyd2isrequiredfordefinitehematopoieticstemcellproductioninthemouseembryo
AT brownmarka thelysinemethyltransferasesmyd2isrequiredfordefinitehematopoieticstemcellproductioninthemouseembryo
AT alshiraihiilham thelysinemethyltransferasesmyd2isrequiredfordefinitehematopoieticstemcellproductioninthemouseembryo
AT jarrelldillonk thelysinemethyltransferasesmyd2isrequiredfordefinitehematopoieticstemcellproductioninthemouseembryo
AT tuckerhaleyo thelysinemethyltransferasesmyd2isrequiredfordefinitehematopoieticstemcellproductioninthemouseembryo
AT edwardsmelissaa lysinemethyltransferasesmyd2isrequiredfordefinitehematopoieticstemcellproductioninthemouseembryo
AT brownmarka lysinemethyltransferasesmyd2isrequiredfordefinitehematopoieticstemcellproductioninthemouseembryo
AT alshiraihiilham lysinemethyltransferasesmyd2isrequiredfordefinitehematopoieticstemcellproductioninthemouseembryo
AT jarrelldillonk lysinemethyltransferasesmyd2isrequiredfordefinitehematopoieticstemcellproductioninthemouseembryo
AT tuckerhaleyo lysinemethyltransferasesmyd2isrequiredfordefinitehematopoieticstemcellproductioninthemouseembryo