Obligate role of anti-apoptotic MCL-1 in the survival of hematopoietic stem cells

Joseph T. Opferman, Hiromi Iwasaki, Christy C. Ong, Heikyung Suh, Shin Ichi Mizuno, Koichi Akashi, Stanley J. Korsmeyer

Research output: Contribution to journalArticlepeer-review

422 Citations (Scopus)

Abstract

Apoptosis is important in controlling hematopoietic stem cell (HSC) numbers. However, the specific BCL-2 family member(s) that regulate HSC homeostasis are not precisely defined. We tested myeloid leukemia-1 (MCL-1) as an attractive candidate that is highly expressed in HSCs and regulated by growth factor signals. Inducible deletion of Mcl-1 in mice resulted in ablation of bone marrow. This resulted in the loss of early bone marrow progenitor populations, including HSCs. Moreover, growth factors including stem cell factor increased transcription of the Mcl-1 gene and required MCL-1 to augment survival of purified bone marrow progenitors. Deletion of Mcl-1 in other tissues, including liver, did not impair survival. Thus, MCL-1 is a critical and specific regulator essential for ensuring the homeostasis of early hematopoietic progenitors.

Original languageEnglish
Pages (from-to)1101-1104
Number of pages4
JournalScience
Volume307
Issue number5712
DOIs
Publication statusPublished - Feb 18 2005
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • General

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