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 language | English |
|---|---|
| Pages (from-to) | 1101-1104 |
| Number of pages | 4 |
| Journal | Science |
| Volume | 307 |
| Issue number | 5712 |
| DOIs | |
| Publication status | Published - Feb 18 2005 |
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All Science Journal Classification (ASJC) codes
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Obligate role of anti-apoptotic MCL-1 in the survival of hematopoietic stem cells. / Opferman, Joseph T.; Iwasaki, Hiromi; Ong, Christy C.; Suh, Heikyung; Mizuno, Shin Ichi; Akashi, Koichi; Korsmeyer, Stanley J.
In: Science, Vol. 307, No. 5712, 18.02.2005, p. 1101-1104.Research output: Contribution to journal › Article
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TY - JOUR
T1 - Obligate role of anti-apoptotic MCL-1 in the survival of hematopoietic stem cells
AU - Opferman, Joseph T.
AU - Iwasaki, Hiromi
AU - Ong, Christy C.
AU - Suh, Heikyung
AU - Mizuno, Shin Ichi
AU - Akashi, Koichi
AU - Korsmeyer, Stanley J.
PY - 2005/2/18
Y1 - 2005/2/18
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=13844319184&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=13844319184&partnerID=8YFLogxK
U2 - 10.1126/science.1106114
DO - 10.1126/science.1106114
M3 - Article
C2 - 15718471
AN - SCOPUS:13844319184
VL - 307
SP - 1101
EP - 1104
JO - Science
JF - Science
SN - 0036-8075
IS - 5712
ER -