Hematopoietic progenitors express neural genes.
Bone marrow, or cells selected from bone marrow, were reported recently to give rise to cells with a neural phenotype after in vitro treatment with neural-inducing factors or after delivery into the brain. However, we showed previously that untreated bone marrow cells express products of the neural myelin basic protein gene, and we demonstrate here that a subset of ex vivo bone marrow cells expresses the neurogenic transcription factor Pax-6 as well as neuronal genes encoding neurofilament H, NeuN (neuronal nuclear protein), HuC/HuD (Hu-antigen C/Hu-antigen D), and GAD65 (glutamic acid decarboxylase 65), as well as the oligodendroglial gene encoding CNPase (2',3' cyclic nucleotide 3'-phosphohydrolase). In contrast, astroglial glial fibrillary acidic protein (GFAP) was not detected. These cells also were CD34+, a marker of hematopoietic stem cells. Cultures of these highly proliferative CD34+ cells, derived from adult mouse bone marrow, uniformly displayed a phenotype comparable with that of hematopoietic progenitor cells (CD45+, CD34+, Sca-1+, AA4.1+, cKit+, GATA-2+, and LMO-2+). The neuronal and oligodendroglial genes expressed in ex vivo bone marrow also were expressed in all cultured CD34+ cells, and GFAP was not observed. After CD34+ cell transplantation into adult brain, neuronal or oligodendroglial markers segregated into distinct nonoverlapping cell populations, whereas astroglial GFAP appeared, in the absence of other neural markers, in a separate set of implanted cells. Thus, neuronal and oligodendroglial gene products are present in a subset of bone marrow cells, and the expression of these genes can be regulated in brain. The fact that these CD34+ cells also express transcription factors (Rex-1 and Oct-4) that are found in early development elicits the hypothesis that they may be pluripotent embryonic-like stem cells.
Goolsby
James
J
Department of Neurology, University of Maryland School of Medicine, and Multiple Sclerosis Center of Excellence, Veterans Affairs Medical Center, Baltimore, MD 21201, USA.
Marty
Marie C
MC
Heletz
Dafna
D
Chiappelli
Joshua
J
Tashko
Gerti
G
Yarnell
Deborah
D
Fishman
Paul S
PS
Dhib-Jalbut
Suhayl
S
Bever
Christopher T
CT
Pessac
Bernard
B
Trisler
David
D
D000818:Animals; D018952:Antigens, CD34 / Q000096:biosynthesis; D015153:Blotting, Western; D001854:Bone Marrow Cells / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D002455:Cell Division; D017690:Cell Transplantation; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D051959:ELAV Proteins; D000067778:ELAV-Like Protein 3; D000067779:ELAV-Like Protein 4; D005136:Eye Proteins; D005904:Glial Fibrillary Acidic Protein / Q000096:biosynthesis; D005968:Glutamate Decarboxylase / Q000096:biosynthesis; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000096:biosynthesis; D007150:Immunohistochemistry; D007377:Interleukin-3 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007527:Isoenzymes / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000096:biosynthesis; D016900:Neurofilament Proteins / Q000096:biosynthesis; D009474:Neurons / Q000378:metabolism*; D050814:Octamer Transcription Factor-3; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; D010641:Phenotype; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000096:biosynthesis; D012097:Repressor Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019089:Stem Cell Factor / Q000378:metabolism; D013997:Time Factors; D014157:Transcription Factors
D018952:Antigens, CD34; D004268:DNA-Binding Proteins; D051959:ELAV Proteins; D000067778:ELAV-Like Protein 3; D000067779:ELAV-Like Protein 4; C490263:Elavl3 protein, mouse; C498011:Elavl4 protein, mouse; D005136:Eye Proteins; D005904:Glial Fibrillary Acidic Protein; D018398:Homeodomain Proteins; D007377:Interleukin-3; D015850:Interleukin-6; D007527:Isoenzymes; D009419:Nerve Tissue Proteins; D016900:Neurofilament Proteins; D050814:Octamer Transcription Factor-3; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; C000605732:Pax6 protein, mouse; C494174:Pou5f1 protein, mouse; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D012097:Repressor Proteins; D019089:Stem Cell Factor; D014157:Transcription Factors; C051774:neurofilament protein H; D005968:Glutamate Decarboxylase; C401141:glutamate decarboxylase 2