SCL expression at critical points in human hematopoietic lineage commitment.
The stem cell leukemia (SCL or tal-1) gene was initially identified as a translocation partner in a leukemia that possessed both lymphoid and myeloid differentiation potential. Mice that lacked SCL expression showed a complete block in hematopoiesis; thus, SCL was associated with hematopoietic stem cell (HSC) function. More recent studies show a role for SCL in murine erythroid differentiation. However, the expression pattern and the role of SCL during early stages of human hematopoietic differentiation are less clear. In this study we chart the pattern of human SCL expression from HSCs, through developmentally sequential populations of lymphoid and myeloid progenitors to mature cells of the hematopoietic lineages. Using recently defined surface immunophenotypes, we fluorescence-activated cell-sorted (FACS) highly purified populations of primary human hematopoietic progenitors for reverse transcription-polymerase chain reaction (RT-PCR) analysis of SCL expression. Our data show that SCL mRNA is easily detectable in all hematopoietic populations with erythroid potential, including HSCs, multipotential progenitors, common myeloid progenitors, megakaryocyte/erythrocyte progenitors, and nucleated erythroid lineage cells. SCL mRNA expression was present but rapidly downregulated in the common lymphoid progenitor and granulocyte/monocyte progenitor populations that lack erythroid potential. SCL expression was undetectable in immature cells of nonerythroid lineages, including pro-B cells, early thymic progenitors, and myeloid precursors expressing the M-CSF receptor. SCL expression was also absent from all mature cells of the nonerythroid lineages. Although low levels of SCL were detected in lymphoid- and myeloid-restricted progenitors, our studies show that abundant SCL expression is normally tightly linked with erythroid differentiation potential.
Zhang
Yanjia
Y
Childrens Hospital Los Angeles, M.S.#62, 4650 Sunset Boulevard, Los Angeles, CA 90027, USA.
Payne
Kimberly J
KJ
Zhu
Yuhua
Y
Price
Mary A
MA
Parrish
Yasmin K
YK
Zielinska
Ewa
E
Barsky
Lora W
LW
Crooks
Gay M
GM
D000818:Animals; D018952:Antigens, CD34 / Q000096:biosynthesis; D051792:Basic Helix-Loop-Helix Proteins; D001854:Bone Marrow Cells / Q000166:cytology; D002454:Cell Differentiation; D002460:Cell Line; D019070:Cell Lineage; D002469:Cell Separation; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000502:physiology*; D015536:Down-Regulation; D005434:Flow Cytometry; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D016130:Immunophenotyping; D051379:Mice; D008954:Models, Biological; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis* / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000166:cytology; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D013950:Thymus Gland / Q000378:metabolism; D013997:Time Factors; D014157:Transcription Factors / Q000096:biosynthesis* / Q000502:physiology*
D018952:Antigens, CD34; D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D014157:Transcription Factors; C067143:TAL1 protein, human