Journal article

Hhex Regulates Hematopoietic Stem Cell Self-Renewal and Stress Hematopoiesis via Repression of Cdkn2a

Jacob T Jackson, Benjamin J Shields, Wei Shi, Ladina Di Rago, Donald Metcalf, Nicos A Nicola, Matthew P McCormack

STEM CELLS | WILEY | Published : 2017

Abstract

The hematopoietically expressed homeobox transcription factor (Hhex) is important for the maturation of definitive hematopoietic progenitors and B-cells during development. We have recently shown that in adult hematopoiesis, Hhex is dispensable for maintenance of hematopoietic stem cells (HSCs) and myeloid lineages but essential for the commitment of common lymphoid progenitors (CLPs) to lymphoid lineages. Here, we show that during serial bone marrow transplantation, Hhex-deleted HSCs are progressively lost, revealing an intrinsic defect in HSC self-renewal. Moreover, Hhex-deleted mice show markedly impaired hematopoietic recovery following myeloablation, due to a failure of progenitor expan..

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Grants


Funding Acknowledgements

We thank Walter and Eliza Hall Institute (WEHI) Bioservices for animal husbandry and the WEHI flow cytometry facility. This work was supported by project grants (1003391 and 1085765, [to M.P.M]) and the Independent Research Institutes Infrastructure Support (IRIIS) Scheme from the Australian Government's National Health and Medical Research Council (NHMRC), a Grant-in-aid from the Cancer Council of Victoria (to M.P.M and W.S.), a Future Fellowship from the Australian Research Council (to M.P.M.), a Centenary Fellowship from Commonwealth Serum Laboratory (CSL) (W.S.), and a Victorian State Government Operational Infrastructure Support (OIS) grant.