Enhancement of hematopoietic stem cell repopulating capacity and self-renewal in the absence of the transcription factor C/EBPα

Pu Zhang; Junko Iwasaki-Arai; Hiromi Iwasaki; Maris L. Fenyus; Tajhal Dayaram; Bronwyn M. Owens; Hirokazu Shigematsu; Elena Levantini; Claudia S. Huettner; Julie A. Lekstrom-Himes; Koichi Akashi; Daniel G. Tenen

doi:10.1016/j.immuni.2004.11.006

Enhancement of hematopoietic stem cell repopulating capacity and self-renewal in the absence of the transcription factor C/EBPα

Pu Zhang, Junko Iwasaki-Arai, Hiromi Iwasaki, Maris L. Fenyus, Tajhal Dayaram, Bronwyn M. Owens, Hirokazu Shigematsu, Elena Levantini, Claudia S. Huettner, Julie A. Lekstrom-Himes, Koichi Akashi, Daniel G. Tenen

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Abstract

The transcription factor C/EBPα is required for granulopoiesis and frequently disrupted in human acute myeloid leukemia (AML). Here, we show disruption of C/EBPα blocks the transition from the common myeloid to the granulocyte/monocyte progenitor but is not required beyond this stage for terminal granulocyte maturation. C/EBPα-deficient hematopoietic stem cells (HSCs) have increased expression of Bmi-1 and enhanced competitive repopulating activity. Bone marrow in adult C/EBPα-deficient mice was filled with myeloblasts, similar to human AML, supporting the notion that disruption of C/EBPα cooperates with other events in the development of leukemia. Therefore, C/EBPα is not only essential for granulocyte development but, in addition, is a regulator of hematopoietic stem cell activity.

Original language	English
Pages (from-to)	853-863
Number of pages	11
Journal	Immunity
Volume	21
Issue number	6
DOIs	https://doi.org/10.1016/j.immuni.2004.11.006
Publication status	Published - Dec 2004
Externally published	Yes

All Science Journal Classification (ASJC) codes

Immunology and Allergy
Immunology
Infectious Diseases

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.immuni.2004.11.006

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Zhang, P., Iwasaki-Arai, J., Iwasaki, H., Fenyus, M. L., Dayaram, T., Owens, B. M., Shigematsu, H., Levantini, E., Huettner, C. S., Lekstrom-Himes, J. A., Akashi, K., & Tenen, D. G. (2004). Enhancement of hematopoietic stem cell repopulating capacity and self-renewal in the absence of the transcription factor C/EBPα. Immunity, 21(6), 853-863. https://doi.org/10.1016/j.immuni.2004.11.006

Zhang, P, Iwasaki-Arai, J, Iwasaki, H, Fenyus, ML, Dayaram, T, Owens, BM, Shigematsu, H, Levantini, E, Huettner, CS, Lekstrom-Himes, JA, Akashi, K & Tenen, DG 2004, 'Enhancement of hematopoietic stem cell repopulating capacity and self-renewal in the absence of the transcription factor C/EBPα', Immunity, vol. 21, no. 6, pp. 853-863. https://doi.org/10.1016/j.immuni.2004.11.006

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title = "Enhancement of hematopoietic stem cell repopulating capacity and self-renewal in the absence of the transcription factor C/EBPα",

abstract = "The transcription factor C/EBPα is required for granulopoiesis and frequently disrupted in human acute myeloid leukemia (AML). Here, we show disruption of C/EBPα blocks the transition from the common myeloid to the granulocyte/monocyte progenitor but is not required beyond this stage for terminal granulocyte maturation. C/EBPα-deficient hematopoietic stem cells (HSCs) have increased expression of Bmi-1 and enhanced competitive repopulating activity. Bone marrow in adult C/EBPα-deficient mice was filled with myeloblasts, similar to human AML, supporting the notion that disruption of C/EBPα cooperates with other events in the development of leukemia. Therefore, C/EBPα is not only essential for granulocyte development but, in addition, is a regulator of hematopoietic stem cell activity.",

author = "Pu Zhang and Junko Iwasaki-Arai and Hiromi Iwasaki and Fenyus, {Maris L.} and Tajhal Dayaram and Owens, {Bronwyn M.} and Hirokazu Shigematsu and Elena Levantini and Huettner, {Claudia S.} and Lekstrom-Himes, {Julie A.} and Koichi Akashi and Tenen, {Daniel G.}",

note = "Funding Information: We acknowledge Tracey Lodie for assistance with breeding and analysis of C/EBPα −/− mice; Gary Gilliland and Liqin Liu, as well as Frank Rosenbauer and other members of the Akashi and Tenen labs for valuable suggestions; Joel Lawitts and the Beth Israel Deaconess Medical Center Transgenic Facility for assistance in rederivation of mice; Maris Handley for cell sorting and analysis; and Alison Lugay for assistance with preparation of the manuscript. This work was supplied by National Institutes of Health grants HL56745 and CA72009 to D.G.T. and CA78045 to K.A. ",

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AU - Fenyus, Maris L.

AU - Dayaram, Tajhal

AU - Owens, Bronwyn M.

AU - Shigematsu, Hirokazu

AU - Levantini, Elena

AU - Huettner, Claudia S.

AU - Lekstrom-Himes, Julie A.

AU - Akashi, Koichi

AU - Tenen, Daniel G.

N1 - Funding Information: We acknowledge Tracey Lodie for assistance with breeding and analysis of C/EBPα −/− mice; Gary Gilliland and Liqin Liu, as well as Frank Rosenbauer and other members of the Akashi and Tenen labs for valuable suggestions; Joel Lawitts and the Beth Israel Deaconess Medical Center Transgenic Facility for assistance in rederivation of mice; Maris Handley for cell sorting and analysis; and Alison Lugay for assistance with preparation of the manuscript. This work was supplied by National Institutes of Health grants HL56745 and CA72009 to D.G.T. and CA78045 to K.A.

PY - 2004/12

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AB - The transcription factor C/EBPα is required for granulopoiesis and frequently disrupted in human acute myeloid leukemia (AML). Here, we show disruption of C/EBPα blocks the transition from the common myeloid to the granulocyte/monocyte progenitor but is not required beyond this stage for terminal granulocyte maturation. C/EBPα-deficient hematopoietic stem cells (HSCs) have increased expression of Bmi-1 and enhanced competitive repopulating activity. Bone marrow in adult C/EBPα-deficient mice was filled with myeloblasts, similar to human AML, supporting the notion that disruption of C/EBPα cooperates with other events in the development of leukemia. Therefore, C/EBPα is not only essential for granulocyte development but, in addition, is a regulator of hematopoietic stem cell activity.

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Enhancement of hematopoietic stem cell repopulating capacity and self-renewal in the absence of the transcription factor C/EBPα

Abstract

All Science Journal Classification (ASJC) codes

UN SDGs

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