Differential mRNA processing in hematopoietic stem cells.
Hematopoietic stem cells (HSCs) maintain tissue homeostasis by rapidly responding to environmental changes. Although this function is well understood, the molecular mechanisms governing this characteristic are largely unknown. We used a sequenced-based strategy to explore the role of both transcriptional and post-transcriptional regulation in HSC biology. We characterized the gene expression differences between HSCs, both quiescent and proliferating, and their differentiated progeny. This analysis revealed a large fraction of sequence tags aligned to intronic sequences, which we showed were derived from unspliced transcripts. A comparison of the biological properties of the observed spliced versus unspliced transcripts in HSCs showed that the unspliced transcripts were enriched in genes involved in DNA binding and RNA processing. In addition, levels of unspliced message decreased in a transcript-specific fashion after HSC activation in vivo. This change in unspliced transcript level coordinated with increases in gene expression of splicing machinery components. Combined, these results suggest that post-transcriptional regulation is important in HSC activation in vivo.
Bowman
Teresa V
TV
Cell and Gene Therapy Center, Baylor College of Medicine, N1030, One Baylor Plaza, Houston, Texas 77030, USA.
McCooey
Andrew J
AJ
Merchant
Akil A
AA
Ramos
Carlos A
CA
Fonseca
Patricia
P
Poindexter
Alan
A
Bradfute
Steven B
SB
Oliveira
Daniela M
DM
Green
Rahshaana
R
Zheng
Yayun
Y
Jackson
Kathyjo A
KA
Chambers
Stuart M
SM
McKinney-Freeman
Shannon L
SL
Norwood
Kevin G
KG
Darlington
Gretchen
G
Gunaratne
Preethi H
PH
Steffen
David
D
Goodell
Margaret A
MA
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000502:physiology; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000502:physiology*; D006706:Homeostasis / Q000502:physiology; D051379:Mice; D012326:RNA Splicing / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods