NDLI: PR-domain–containing Mds1-Evi1 is critical for long-term hematopoietic stem cell function

Content Provider	PubMed Central
Author	Zhang, Yi Sandra, Stehling-sun Kimberly, Lezon-geyda Juneja, Subhash C. Coillard, Lucie Chatterjee, Gouri Wuertzer, Charles A. Camargo, Fernando Perkins, Archibald S.
Copyright Year	2011
Abstract	The Mds1 and Evi1 complex locus (Mecom) gives rise to several alternative transcripts implicated in leukemogenesis. However, the contribution that Mecom-derived gene products make to normal hematopoiesis remains largely unexplored. To investigate the role of the upstream transcription start site of Mecom in adult hematopoiesis, we created a mouse model with a lacZ knock-in at this site, termed ME m1, which eliminates Mds1-Evi1 (ME), the longer, PR-domain–containing isoform produced by the gene (also known as PRDM3). β-galactosidase–marking studies revealed that, within hematopoietic cells, ME is exclusively expressed in the stem cell compartment. ME deficiency leads to a reduction in the number of HSCs and a complete loss of long-term repopulation capacity, whereas the stem cell compartment is shifted from quiescence to active cycling. Genetic exploration of the relative roles of endogenous ME and EVI1 isoforms revealed that ME preferentially rescues long-term HSC defects. RNA-seq analysis in Lin−Sca-1+c-Kit+ cells (LSKs) of ME m1 documents near complete silencing of Cdkn1c, encoding negative cell-cycle regulator p57-Kip2. Reintroduction of ME into ME m1 LSKs leads to normalization of both p57-Kip2 expression and growth control. Our results clearly demonstrate a critical role of PR-domain–containing ME in linking p57-kip2 regulation to long-term HSC function.
Related Links	http://dx.doi.org/10.1182/blood-2011-02-334680
Ending Page	3861
Page Count	9
Starting Page	3853
File Format	PDF
ISSN	00064971
e-ISSN	15280020
Journal	Blood
Issue Number	14
Volume Number	118
Language	English
Publisher	American Society of Hematology
Publisher Date	2011-10-06
Access Restriction	Open
Rights Holder	American Society of Hematology
Subject Keyword	Immunology Cell Biology Biochemistry Hematology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Cell Biology Hematology Biochemistry Immunology

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