Embryonic stem cells and transgenic mice in the study of hematopoiesis.

Blood formation (hematopoiesis) entails the generation of hematopoietic stem cells (HSCs) within the embryo and subsequent commitment of multipotential progenitors to differentiation along single lineages. These processes are controlled in large part by cell-restricted transcription factors which cooperate with more widely expressed factors to direct lineage-specific gene expression. Candidate hematopoietic transcriptional regulators have been identified by characterizing factors mediating cell-specific gene transcription and by defining genes involved in chromosomal rearrangements in leukemia. The application of transgenic and embryonic stem cell methods have provided insights into their in vivo functions and suggested mechanisms by which lineage selection may be achieved. One of the first, and best, characterized hematopoietic transcription factors is GATA-1. Herein studies of GATA-1 are reviewed to illustrate how manipulations of its locus in the mouse have contributed to current understanding in unique and unexpected ways.

[1]  S. Orkin,et al.  Failure of megakaryopoiesis and arrested erythropoiesis in mice lacking the GATA-1 transcriptional cofactor FOG. , 1998, Genes & development.

[2]  S. Orkin,et al.  Unsuspected role for the T-cell leukemia protein SCL/tal-1 in vascular development. , 1998, Genes & development.

[3]  W. Gelbart,et al.  u-shaped encodes a zinc finger protein that regulates the proneural genes achaete and scute during the formation of bristles in Drosophila. , 1997, Genes & development.

[4]  P. Simpson,et al.  Transcriptional activity of pannier is regulated negatively by heterodimerization of the GATA DNA-binding domain with a cofactor encoded by the u-shaped gene of Drosophila. , 1997, Genes & development.

[5]  D. Bodine,et al.  Characterization of definitive lymphohematopoietic stem cells in the day 9 murine yolk sac. , 1997, Immunity.

[6]  S. Orkin,et al.  An upstream, DNase I hypersensitive region of the hematopoietic-expressed transcription factor GATA-1 gene confers developmental specificity in transgenic mice. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[7]  S. Orkin,et al.  FOG, a Multitype Zinc Finger Protein, Acts as a Cofactor for Transcription Factor GATA-1 in Erythroid and Megakaryocytic Differentiation , 1997, Cell.

[8]  S. Orkin,et al.  A lineage‐selective knockout establishes the critical role of transcription factor GATA‐1 in megakaryocyte growth and platelet development , 1997, The EMBO journal.

[9]  S. Orkin,et al.  A "knockdown" mutation created by cis-element gene targeting reveals the dependence of erythroid cell maturation on the level of transcription factor GATA-1. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[10]  T. Rabbitts,et al.  The LIM‐only protein Lmo2 is a bridging molecule assembling an erythroid, DNA‐binding complex which includes the TAL1, E47, GATA‐1 and Ldb1/NLI proteins , 1997, The EMBO journal.

[11]  M. Greaves,et al.  Multilineage gene expression precedes commitment in the hemopoietic system. , 1997, Genes & development.

[12]  S. Orkin,et al.  Erythroid-cell-specific properties of transcription factor GATA-1 revealed by phenotypic rescue of a gene-targeted cell line , 1997, Molecular and cellular biology.

[13]  D A Kane,et al.  Characterization of zebrafish mutants with defects in embryonic hematopoiesis. , 1996, Development.

[14]  Y Fujiwara,et al.  Arrested development of embryonic red cell precursors in mouse embryos lacking transcription factor GATA-1. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[15]  P. Leder,et al.  Tal‐1 induces T cell acute lymphoblastic leukemia accelerated by casein kinase IIalpha. , 1996, The EMBO journal.

[16]  S. Orkin.  Development of the hematopoietic system. , 1996, Current opinion in genetics & development.

[17]  A. Medvinsky,et al.  Definitive Hematopoiesis Is Autonomously Initiated by the AGM Region , 1996, Cell.

[18]  C. Begley,et al.  The scl gene product is required for the generation of all hematopoietic lineages in the adult mouse. , 1996, The EMBO journal.

[19]  F. Alt,et al.  The T Cell Leukemia Oncoprotein SCL/tal-1 Is Essential for Development of All Hematopoietic Lineages , 1996, Cell.

[20]  T. Graf,et al.  MafB Is an Interaction Partner and Repressor of Ets-1 That Inhibits Erythroid Differentiation , 1996, Cell.

[21]  T. Rabbitts,et al.  Protein dimerization between Lmo2 (Rbtn2) and Tal1 alters thymocyte development and potentiates T cell tumorigenesis in transgenic mice. , 1996, The EMBO journal.

[22]  S. Orkin,et al.  Transcription factor GATA-1 permits survival and maturation of erythroid precursors by preventing apoptosis. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[23]  T. Ley,et al.  Targeted deletion of 5'HS2 of the murine beta-globin LCR reveals that it is not essential for proper regulation of the beta-globin locus. , 1995, Genes & development.

[24]  C. Begley,et al.  Absence of yolk sac hematopoiesis from mice with a targeted disruption of the scl gene. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[25]  T. Graf,et al.  GATA-1 reprograms avian myelomonocytic cell lines into eosinophils, thromboblasts, and erythroblasts. , 1995, Genes & development.

[26]  S. Orkin,et al.  Absence of blood formation in mice lacking the T-cell leukaemia oncoprotein tal-1/SCL , 1995, Nature.

[27]  S. Orkin,et al.  The C-terminal zinc finger of GATA-1 or GATA-2 is sufficient to induce megakaryocytic differentiation of an early myeloid cell line , 1995, Molecular and cellular biology.

[28]  T. Rabbitts,et al.  Chromosomal translocations in human cancer , 1994, Nature.

[29]  J. Li,et al.  Specific in vivo association between the bHLH and LIM proteins implicated in human T cell leukemia. , 1994, The EMBO journal.

[30]  Stuart H. Orkin,et al.  An early haematopoietic defect in mice lacking the transcription factor GATA-2 , 1994, Nature.

[31]  M. Evans,et al.  The Oncogenic Cysteine-rich LIM domain protein Rbtn2 is essential for erythroid development , 1994, Cell.

[32]  K. Rajewsky,et al.  Deletion of a DNA polymerase beta gene segment in T cells using cell type-specific gene targeting. , 1994, Science.

[33]  G. Keller,et al.  Novel insights into erythroid development revealed through in vitro differentiation of GATA-1 embryonic stem cells. , 1994, Genes & development.

[34]  A. Müller,et al.  An early pre-liver intraembryonic source of CFU-S in the developing mouse , 1993, Nature.

[35]  J. D. Engel,et al.  Erythroid transcription factor GATA-1 is abundantly transcribed in mouse testis , 1993, Nature.

[36]  J. Visvader,et al.  GATA‐1 but not SCL induces megakaryocytic differentiation in an early myeloid line. , 1992, The EMBO journal.

[37]  S. Orkin,et al.  The SCL gene product: a positive regulator of erythroid differentiation. , 1992, The EMBO journal.

[38]  J. Visvader,et al.  SCL is coexpressed with GATA-1 in hemopoietic cells but is also expressed in developing brain. , 1992, Oncogene.

[39]  S. Orkin,et al.  Erythroid differentiation in chimaeric mice blocked by a targeted mutation in the gene for transcription factor GATA-1 , 1991, Nature.

[40]  S. Orkin,et al.  Transcriptional activation and DNA binding by the erythroid factor GF-1/NF-E1/Eryf 1. , 1990, Genes & development.

[41]  Stuart H. Orkin,et al.  Expression of an erythroid transcription factor in megakaryocytic and mast cell lineages , 1990, Nature.

[42]  T. Waldmann,et al.  The gene SCL is expressed during early hematopoiesis and encodes a differentiation-related DNA-binding motif. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[43]  G. Felsenfeld,et al.  The erythroid-specific transcription factor eryf1: A new finger protein , 1989, Cell.

[44]  Shih-Feng Tsai,et al.  Cloning of cDNA for the major DNA-binding protein of the erythroid lineage through expression in mammalian cells , 1989, Nature.

[45]  W. Schaffner,et al.  A cloned octamer transcription factor stimulates transcription from lymphoid–specific promoters in non–B cells , 1988, Nature.

[46]  P. Sharp,et al.  Cloning of a lymphoid-specific cDNA encoding a protein binding the regulatory octamer DNA motif. , 1988, Science.

[47]  H. Weintraub,et al.  Expression of a single transfected cDNA converts fibroblasts to myoblasts , 1987, Cell.

[48]  S. Orkin.  Hematopoiesis: how does it happen? , 1995, Current opinion in cell biology.

[49]  M. Wiles,et al.  Hematopoietic commitment during embryonic stem cell differentiation in culture. , 1993, Molecular and cellular biology.