Let-7 microRNAs are developmentally regulated in circulating human erythroid cells

Seung Jae Noh, Samuel H. Miller, Y. Terry Lee, Sung Ho Goh, Francesco M. Marincola, David F. Stroncek, Christopher Reed, Ena Wang, Jeffery L. Miller

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Background: MicroRNAs are ~22nt-long small non-coding RNAs that negatively regulate protein expression through mRNA degradation or translational repression in eukaryotic cells. Based upon their importance in regulating development and terminal differentiation in model systems, erythrocyte microRNA profiles were examined at birth and in adults to determine if changes in their abundance coincide with the developmental phenomenon of hemoglobin switching. Methods: Expression profiling of microRNA was performed using total RNA from four adult peripheral blood samples compared to four cord blood samples after depletion of plasma, platelets, and nucleated cells. Labeled RNAs were hybridized to custom spotted arrays containing 474 human microRNA species (miRBase release 9.1). Total RNA from Epstein-Barr virus (EBV)-transformed lymphoblastoid cell lines provided a hybridization reference for all samples to generate microRNA abundance profile for each sample. Results: Among 206 detected miRNAs, 79% of the microRNAs were present at equivalent levels in both cord and adult cells. By comparison, 37 microRNAs were up-regulated and 4 microRNAs were down-regulated in adult erythroid cells (fold change > 2; p < 0.01). Among the up-regulated subset, the let-7 miRNA family consistently demonstrated increased abundance in the adult samples by array-based analyses that were confirmed by quantitative PCR (4.5 to 18.4 fold increases in 6 of 8 let-7 miRNA). Profiling studies of messenger RNA (mRNA) in these cells additionally demonstrated down-regulation of ten let-7 target genes in the adult cells. Conclusion: These data suggest that a consistent pattern of up-regulation among let-7 miRNA in circulating erythroid cells occurs in association with hemoglobin switching during the fetal-to-adult developmental transition in humans.

Original languageEnglish
Article number98
JournalJournal of Translational Medicine
Volume7
DOIs
Publication statusPublished - 25 Nov 2009
Externally publishedYes

Fingerprint

Erythroid Cells
MicroRNAs
RNA
Hemoglobins
Blood
Long Noncoding RNA
Small Untranslated RNA
Messenger RNA
Transformed Cell Line
RNA Stability
Eukaryotic Cells
Platelets
Human Herpesvirus 4
Fetal Blood
Viruses
Up-Regulation
Blood Platelets
Down-Regulation
Genes
Erythrocytes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Noh, S. J., Miller, S. H., Lee, Y. T., Goh, S. H., Marincola, F. M., Stroncek, D. F., ... Miller, J. L. (2009). Let-7 microRNAs are developmentally regulated in circulating human erythroid cells. Journal of Translational Medicine, 7, [98]. https://doi.org/10.1186/1479-5876-7-98

Let-7 microRNAs are developmentally regulated in circulating human erythroid cells. / Noh, Seung Jae; Miller, Samuel H.; Lee, Y. Terry; Goh, Sung Ho; Marincola, Francesco M.; Stroncek, David F.; Reed, Christopher; Wang, Ena; Miller, Jeffery L.

In: Journal of Translational Medicine, Vol. 7, 98, 25.11.2009.

Research output: Contribution to journalArticle

Noh, SJ, Miller, SH, Lee, YT, Goh, SH, Marincola, FM, Stroncek, DF, Reed, C, Wang, E & Miller, JL 2009, 'Let-7 microRNAs are developmentally regulated in circulating human erythroid cells', Journal of Translational Medicine, vol. 7, 98. https://doi.org/10.1186/1479-5876-7-98
Noh, Seung Jae ; Miller, Samuel H. ; Lee, Y. Terry ; Goh, Sung Ho ; Marincola, Francesco M. ; Stroncek, David F. ; Reed, Christopher ; Wang, Ena ; Miller, Jeffery L. / Let-7 microRNAs are developmentally regulated in circulating human erythroid cells. In: Journal of Translational Medicine. 2009 ; Vol. 7.
@article{309628ab9aa44e409a12b30a81fa93d5,
title = "Let-7 microRNAs are developmentally regulated in circulating human erythroid cells",
abstract = "Background: MicroRNAs are ~22nt-long small non-coding RNAs that negatively regulate protein expression through mRNA degradation or translational repression in eukaryotic cells. Based upon their importance in regulating development and terminal differentiation in model systems, erythrocyte microRNA profiles were examined at birth and in adults to determine if changes in their abundance coincide with the developmental phenomenon of hemoglobin switching. Methods: Expression profiling of microRNA was performed using total RNA from four adult peripheral blood samples compared to four cord blood samples after depletion of plasma, platelets, and nucleated cells. Labeled RNAs were hybridized to custom spotted arrays containing 474 human microRNA species (miRBase release 9.1). Total RNA from Epstein-Barr virus (EBV)-transformed lymphoblastoid cell lines provided a hybridization reference for all samples to generate microRNA abundance profile for each sample. Results: Among 206 detected miRNAs, 79{\%} of the microRNAs were present at equivalent levels in both cord and adult cells. By comparison, 37 microRNAs were up-regulated and 4 microRNAs were down-regulated in adult erythroid cells (fold change > 2; p < 0.01). Among the up-regulated subset, the let-7 miRNA family consistently demonstrated increased abundance in the adult samples by array-based analyses that were confirmed by quantitative PCR (4.5 to 18.4 fold increases in 6 of 8 let-7 miRNA). Profiling studies of messenger RNA (mRNA) in these cells additionally demonstrated down-regulation of ten let-7 target genes in the adult cells. Conclusion: These data suggest that a consistent pattern of up-regulation among let-7 miRNA in circulating erythroid cells occurs in association with hemoglobin switching during the fetal-to-adult developmental transition in humans.",
author = "Noh, {Seung Jae} and Miller, {Samuel H.} and Lee, {Y. Terry} and Goh, {Sung Ho} and Marincola, {Francesco M.} and Stroncek, {David F.} and Christopher Reed and Ena Wang and Miller, {Jeffery L.}",
year = "2009",
month = "11",
day = "25",
doi = "10.1186/1479-5876-7-98",
language = "English",
volume = "7",
journal = "Journal of Translational Medicine",
issn = "1479-5876",
publisher = "BioMed Central",

}

TY - JOUR

T1 - Let-7 microRNAs are developmentally regulated in circulating human erythroid cells

AU - Noh, Seung Jae

AU - Miller, Samuel H.

AU - Lee, Y. Terry

AU - Goh, Sung Ho

AU - Marincola, Francesco M.

AU - Stroncek, David F.

AU - Reed, Christopher

AU - Wang, Ena

AU - Miller, Jeffery L.

PY - 2009/11/25

Y1 - 2009/11/25

N2 - Background: MicroRNAs are ~22nt-long small non-coding RNAs that negatively regulate protein expression through mRNA degradation or translational repression in eukaryotic cells. Based upon their importance in regulating development and terminal differentiation in model systems, erythrocyte microRNA profiles were examined at birth and in adults to determine if changes in their abundance coincide with the developmental phenomenon of hemoglobin switching. Methods: Expression profiling of microRNA was performed using total RNA from four adult peripheral blood samples compared to four cord blood samples after depletion of plasma, platelets, and nucleated cells. Labeled RNAs were hybridized to custom spotted arrays containing 474 human microRNA species (miRBase release 9.1). Total RNA from Epstein-Barr virus (EBV)-transformed lymphoblastoid cell lines provided a hybridization reference for all samples to generate microRNA abundance profile for each sample. Results: Among 206 detected miRNAs, 79% of the microRNAs were present at equivalent levels in both cord and adult cells. By comparison, 37 microRNAs were up-regulated and 4 microRNAs were down-regulated in adult erythroid cells (fold change > 2; p < 0.01). Among the up-regulated subset, the let-7 miRNA family consistently demonstrated increased abundance in the adult samples by array-based analyses that were confirmed by quantitative PCR (4.5 to 18.4 fold increases in 6 of 8 let-7 miRNA). Profiling studies of messenger RNA (mRNA) in these cells additionally demonstrated down-regulation of ten let-7 target genes in the adult cells. Conclusion: These data suggest that a consistent pattern of up-regulation among let-7 miRNA in circulating erythroid cells occurs in association with hemoglobin switching during the fetal-to-adult developmental transition in humans.

AB - Background: MicroRNAs are ~22nt-long small non-coding RNAs that negatively regulate protein expression through mRNA degradation or translational repression in eukaryotic cells. Based upon their importance in regulating development and terminal differentiation in model systems, erythrocyte microRNA profiles were examined at birth and in adults to determine if changes in their abundance coincide with the developmental phenomenon of hemoglobin switching. Methods: Expression profiling of microRNA was performed using total RNA from four adult peripheral blood samples compared to four cord blood samples after depletion of plasma, platelets, and nucleated cells. Labeled RNAs were hybridized to custom spotted arrays containing 474 human microRNA species (miRBase release 9.1). Total RNA from Epstein-Barr virus (EBV)-transformed lymphoblastoid cell lines provided a hybridization reference for all samples to generate microRNA abundance profile for each sample. Results: Among 206 detected miRNAs, 79% of the microRNAs were present at equivalent levels in both cord and adult cells. By comparison, 37 microRNAs were up-regulated and 4 microRNAs were down-regulated in adult erythroid cells (fold change > 2; p < 0.01). Among the up-regulated subset, the let-7 miRNA family consistently demonstrated increased abundance in the adult samples by array-based analyses that were confirmed by quantitative PCR (4.5 to 18.4 fold increases in 6 of 8 let-7 miRNA). Profiling studies of messenger RNA (mRNA) in these cells additionally demonstrated down-regulation of ten let-7 target genes in the adult cells. Conclusion: These data suggest that a consistent pattern of up-regulation among let-7 miRNA in circulating erythroid cells occurs in association with hemoglobin switching during the fetal-to-adult developmental transition in humans.

UR - http://www.scopus.com/inward/record.url?scp=72549098210&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=72549098210&partnerID=8YFLogxK

U2 - 10.1186/1479-5876-7-98

DO - 10.1186/1479-5876-7-98

M3 - Article

VL - 7

JO - Journal of Translational Medicine

JF - Journal of Translational Medicine

SN - 1479-5876

M1 - 98

ER -