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 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.

journal_name

Sci Rep

journal_title

Scientific reports

authors

Rajasekhar M,Schmitz U,Flamant S,Wong JJ,Bailey CG,Ritchie W,Holst J,Rasko JEJ

doi

10.1038/s41598-018-24203-7

subject

Has Abstract

pub_date

2018-05-08 00:00:00

pages

7264

issue

1

issn

2045-2322

pii

10.1038/s41598-018-24203-7

journal_volume

8

pub_type

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