Gene Expression Profile of Murine Long-term Reconstituting Vs. Short-term Reconstituting Hematopoietic Stem Cells

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2005 Feb 8

PMID 15695585

Citations 33

Authors

Jiang F Zhong

Yi Zhao

Susan Sutton

Andrew Su

Yuxia Zhan

Lunjian Zhu

Chunli Yan

Tim Gallaher

Patrick B Johnston

W French Anderson

Michael P Cooke

Affiliations

Soon will be listed here.

Abstract

The hematopoietic stem cell (HSC) compartment is composed of long-term reconstituting (LTR) and short-term reconstituting (STR) stem cells. LTR HSC can reconstitute the hematopoietic system for life, whereas STR HSC can sustain hematopoiesis for only a few weeks in the mouse. Several excellent gene expression profiles have been obtained of the total hematopoietic stem cell population. We have used five-color FACS sorting to isolate separate populations of LTR and STR stem cell subsets. The LTR HSC has the phenotype defined as Lin- Sca+ Kit+ 38+ 34-; two subsets of STR HSC were obtained with phenotypes of Lin- Sca+ Kit+ 38+ 34+ and Lin- Sca+ Kit+ 38- 34+. The microarray profiling study reported here was able to identify genes specific for LTR functions. In the interrogated genes (approximately 12,000 probe sets corresponding to 8,000 genes), 210 genes are differentially expressed, and 72 genes are associated with LTR activity, including membrane proteins, signal transduction molecules, and transcription factors. Hierarchical clustering of the 210 differentially expressed genes suggested that they are not bone marrow-specific but rather appear to be stem cell-specific. Transcription factor-binding site analysis suggested that GATA3 might play an important role in the biology of LTR HSC.

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References

Harrison D, Zhong R . The same exhaustible multilineage precursor produces both myeloid and lymphoid cells as early as 3-4 weeks after marrow transplantation. Proc Natl Acad Sci U S A. 1992; 89(21):10134-8. PMC: 50292. DOI: 10.1073/pnas.89.21.10134. View

Udagawa N, Takahashi N, Akatsu T, Tanaka H, Sasaki T, Nishihara T . Origin of osteoclasts: mature monocytes and macrophages are capable of differentiating into osteoclasts under a suitable microenvironment prepared by bone marrow-derived stromal cells. Proc Natl Acad Sci U S A. 1990; 87(18):7260-4. PMC: 54723. DOI: 10.1073/pnas.87.18.7260. View

Morrison S, Weissman I . The long-term repopulating subset of hematopoietic stem cells is deterministic and isolatable by phenotype. Immunity. 1994; 1(8):661-73. DOI: 10.1016/1074-7613(94)90037-x. View

Uchida N, Jerabek L, Weissman I . Searching for hematopoietic stem cells. II. The heterogeneity of Thy-1.1(lo)Lin(-/lo)Sca-1+ mouse hematopoietic stem cells separated by counterflow centrifugal elutriation. Exp Hematol. 1996; 24(5):649-59. View

Randall T, Lund F, HOWARD M, Weissman I . Expression of murine CD38 defines a population of long-term reconstituting hematopoietic stem cells. Blood. 1996; 87(10):4057-67. View

Zhong R, Astle C, Harrison D . Distinct developmental patterns of short-term and long-term functioning lymphoid and myeloid precursors defined by competitive limiting dilution analysis in vivo. J Immunol. 1996; 157(1):138-45. View

Osawa M, Hanada K, Hamada H, Nakauchi H . Long-term lymphohematopoietic reconstitution by a single CD34-low/negative hematopoietic stem cell. Science. 1996; 273(5272):242-5. DOI: 10.1126/science.273.5272.242. View

Goodell M, Rosenzweig M, Kim H, Marks D, Demaria M, Paradis G . Dye efflux studies suggest that hematopoietic stem cells expressing low or undetectable levels of CD34 antigen exist in multiple species. Nat Med. 1997; 3(12):1337-45. DOI: 10.1038/nm1297-1337. View

Zanjani E, Almeida-Porada G, Livingston A, Flake A, Ogawa M . Human bone marrow CD34- cells engraft in vivo and undergo multilineage expression that includes giving rise to CD34+ cells. Exp Hematol. 1998; 26(4):353-60. View

10.

Dagher R, Hiatt K, Traycoff C, Srour E, Yoder M . c-Kit and CD38 are expressed by long-term reconstituting hematopoietic cells present in the murine yolk sac. Biol Blood Marrow Transplant. 1998; 4(2):69-74. DOI: 10.1053/bbmt.1998.v4.pm9763109. View

11.

Zhang D, Yang L, Ray A . Differential responsiveness of the IL-5 and IL-4 genes to transcription factor GATA-3. J Immunol. 1998; 161(8):3817-21. View

12.

Novelli E, Ramirez M, Civin C . Biology of CD34+CD38- cells in lymphohematopoiesis. Leuk Lymphoma. 1998; 31(3-4):285-93. DOI: 10.3109/10428199809059221. View

13.

Zanjani E, Almeida-Porada G, Livingston A, Porada C, Ogawa M . Engraftment and multilineage expression of human bone marrow CD34- cells in vivo. Ann N Y Acad Sci. 1999; 872:220-31; discussion 231-2. DOI: 10.1111/j.1749-6632.1999.tb08467.x. View

14.

Sato T, Laver J, Ogawa M . Reversible expression of CD34 by murine hematopoietic stem cells. Blood. 1999; 94(8):2548-54. View

15.

Phillips R, Ernst R, Brunk B, Ivanova N, Mahan M, Deanehan J . The genetic program of hematopoietic stem cells. Science. 2000; 288(5471):1635-40. DOI: 10.1126/science.288.5471.1635. View

16.

Lim K, Lakshmanan G, Crawford S, Gu Y, Grosveld F, Engel J . Gata3 loss leads to embryonic lethality due to noradrenaline deficiency of the sympathetic nervous system. Nat Genet. 2000; 25(2):209-12. DOI: 10.1038/76080. View

17.

Tong Q, Dalgin G, Xu H, Ting C, Leiden J, Hotamisligil G . Function of GATA transcription factors in preadipocyte-adipocyte transition. Science. 2000; 290(5489):134-8. DOI: 10.1126/science.290.5489.134. View

18.

Zhao Y, Lin Y, Zhan Y, Yang G, LOUIE J, Harrison D . Murine hematopoietic stem cell characterization and its regulation in BM transplantation. Blood. 2000; 96(9):3016-22. View

19.

Tajima F, Deguchi T, Laver J, Zeng H, Ogawa M . Reciprocal expression of CD38 and CD34 by adult murine hematopoietic stem cells. Blood. 2001; 97(9):2618-24. DOI: 10.1182/blood.v97.9.2618. View

20.

Lee G, Fields P, Flavell R . Regulation of IL-4 gene expression by distal regulatory elements and GATA-3 at the chromatin level. Immunity. 2001; 14(4):447-59. DOI: 10.1016/s1074-7613(01)00125-x. View