HMGA2 promotes long-term engraftment and myeloerythroid differentiation of human hematopoietic stem and progenitor cells

Blood Advances
Praveen KumarJonas Larsson

Abstract

Identification of determinants of fate choices in hematopoietic stem cells (HSCs) is essential to improve the clinical use of HSCs and to enhance our understanding of the biology of normal and malignant hematopoiesis. Here, we show that high-mobility group AT hook 2 (HMGA2), a nonhistone chromosomal-binding protein, is highly and preferentially expressed in HSCs and in the most immature progenitor cell subset of fetal, neonatal, and adult human hematopoiesis. Knockdown of HMGA2 by short hairpin RNA impaired the long-term hematopoietic reconstitution of cord blood (CB)-derived CB CD34+ cells. Conversely, overexpression of HMGA2 in CB CD34+ cells led to overall enhanced reconstitution in serial transplantation assays accompanied by a skewing toward the myeloerythroid lineages. RNA-sequencing analysis showed that enforced HMGA2 expression in CD34+ cells induced gene-expression signatures associated with differentiation toward megakaryocyte-erythroid and myeloid lineages, as well as signatures associated with growth and survival, which at the protein level were coupled with strong activation of AKT. Taken together, our findings demonstrate a key role of HMGA2 in regulation of both proliferation and differentiation of human HSPCs.

References

Apr 3, 2007·Nature Genetics·Madhu S KumarTyler Jacks
Feb 26, 2008·Cell·Stuart H Orkin, Leonard I Zon
Mar 1, 2008·Proceedings of the National Academy of Sciences of the United States of America·Madhu S KumarTyler Jacks
Feb 7, 2009·Cell Cycle·Miranda Buitenhuis, Paul J Coffer
Jun 2, 2009·Nature Genetics·Srinivas R ViswanathanGeorge Q Daley
Sep 17, 2010·Nature·Marina Cavazzana-CalvoPhilippe Leboulch
Oct 29, 2010·Genome Biology·Simon Anders, Wolfgang Huber
Feb 4, 2011·Experimental Hematology·June Li
Nov 13, 2012·Cell Stem Cell·Eric R LechmanLuigi Naldini
Nov 28, 2012·Developmental Cell·Zhizhong LiDavid J Glass
Sep 1, 2015·Journal of Cancer Research and Clinical Oncology·Li TanHuo Tan
Jul 13, 2016·The Journal of Experimental Medicine·R Grant RoweGeorge Q Daley

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Citations

Jan 23, 2020·International Journal of Molecular Sciences·Robert Vignali, Silvia Marracci
Jan 16, 2020·International Journal of Molecular Sciences·Silvia ParisiTommaso Russo
Aug 28, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Titus Ime EkanemKuen-Haur Lee
Oct 13, 2021·Hematological Oncology·Marco De MartinoAlfredo Fusco

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