Identifying microRNA determinants of human myelopoiesis

Abstract Myelopoiesis involves differentiation of hematopoietic stem cells to cellular populations that are restricted in their self-renewal capacity, beginning with the common myeloid progenitor (CMP) and leading to mature cells including monocytes and granulocytes. This complex process is regulate...

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Autores principales:	Megha Rajasekhar, Ulf Schmitz, Stephane Flamant, Justin J.-L. Wong, Charles G. Bailey, William Ritchie, Jeff Holst, John E. J. Rasko
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5130f8e3f39c40e099172e258a4f2129
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spelling	oai:doaj.org-article:5130f8e3f39c40e099172e258a4f21292021-12-02T16:07:50ZIdentifying microRNA determinants of human myelopoiesis10.1038/s41598-018-24203-72045-2322https://doaj.org/article/5130f8e3f39c40e099172e258a4f21292018-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-24203-7https://doaj.org/toc/2045-2322Abstract Myelopoiesis involves differentiation of hematopoietic stem cells to cellular populations that are restricted in their self-renewal capacity, beginning with the common myeloid progenitor (CMP) and leading to mature cells including monocytes and granulocytes. This complex process is regulated by various extracellular and intracellular signals including microRNAs (miRNAs). We characterised the miRNA profile of human CD34+CD38+ myeloid progenitor cells, and mature monocytes and granulocytes isolated from cord blood using TaqMan Low Density Arrays. We identified 19 miRNAs that increased in both cell types relative to the CMP and 27 that decreased. miR-125b and miR-10a were decreased by 10-fold and 100-fold respectively in the mature cells. Using in vitro granulopoietic differentiation of human CD34+ cells we show that decreases in both miR-125b and miR-10a correlate with a loss of CD34 expression and gain of CD11b and CD15 expression. Candidate target mRNAs were identified by co-incident predictions between the miRanda algorithm and genes with increased expression during differentiation. Using luciferase assays we confirmed MCL1 and FUT4 as targets of miR-125b and the transcription factor KLF4 as a target of miR-10a. Together, our data identify miRNAs with differential expression during myeloid development and reveal some relevant miRNA-target pairs that may contribute to physiological differentiation.Megha RajasekharUlf SchmitzStephane FlamantJustin J.-L. WongCharles G. BaileyWilliam RitchieJeff HolstJohn E. J. RaskoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-15 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Megha Rajasekhar Ulf Schmitz Stephane Flamant Justin J.-L. Wong Charles G. Bailey William Ritchie Jeff Holst John E. J. Rasko Identifying microRNA determinants of human myelopoiesis
description	Abstract Myelopoiesis involves differentiation of hematopoietic stem cells to cellular populations that are restricted in their self-renewal capacity, beginning with the common myeloid progenitor (CMP) and leading to mature cells including monocytes and granulocytes. This complex process is regulated by various extracellular and intracellular signals including microRNAs (miRNAs). We characterised the miRNA profile of human CD34+CD38+ myeloid progenitor cells, and mature monocytes and granulocytes isolated from cord blood using TaqMan Low Density Arrays. We identified 19 miRNAs that increased in both cell types relative to the CMP and 27 that decreased. miR-125b and miR-10a were decreased by 10-fold and 100-fold respectively in the mature cells. Using in vitro granulopoietic differentiation of human CD34+ cells we show that decreases in both miR-125b and miR-10a correlate with a loss of CD34 expression and gain of CD11b and CD15 expression. Candidate target mRNAs were identified by co-incident predictions between the miRanda algorithm and genes with increased expression during differentiation. Using luciferase assays we confirmed MCL1 and FUT4 as targets of miR-125b and the transcription factor KLF4 as a target of miR-10a. Together, our data identify miRNAs with differential expression during myeloid development and reveal some relevant miRNA-target pairs that may contribute to physiological differentiation.
format	article
author	Megha Rajasekhar Ulf Schmitz Stephane Flamant Justin J.-L. Wong Charles G. Bailey William Ritchie Jeff Holst John E. J. Rasko
author_facet	Megha Rajasekhar Ulf Schmitz Stephane Flamant Justin J.-L. Wong Charles G. Bailey William Ritchie Jeff Holst John E. J. Rasko
author_sort	Megha Rajasekhar
title	Identifying microRNA determinants of human myelopoiesis
title_short	Identifying microRNA determinants of human myelopoiesis
title_full	Identifying microRNA determinants of human myelopoiesis
title_fullStr	Identifying microRNA determinants of human myelopoiesis
title_full_unstemmed	Identifying microRNA determinants of human myelopoiesis
title_sort	identifying microrna determinants of human myelopoiesis
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/5130f8e3f39c40e099172e258a4f2129
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Identifying microRNA determinants of human myelopoiesis

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