Molecular portraits of B cell lineage commitment.
In an attempt to characterize early B cell development including the commitment of progenitor cells to the B cell lineage, we generated and compared genomewide gene expression profiles of human hematopoietic stem cells (HSCs) and pre-B cells (PBCs) by using serial analysis of gene expression. From more than 100,000 serial analysis of gene expression tags collected from human CD34(+) HSCs and CD10(+) CD19(+) PBCs, 42,399 unique transcripts were identified in HSCs but only 16,786 in PBCs, suggesting that more than 60% of transcripts expressed in HSCs were silenced during or after commitment to the B cell lineage. On the other hand, mRNAs of pre-B cell receptor (pre-BCR)-associated genes are virtually missing in HSCs but account for more than 10% of the transcriptome of PBCs, which also show increased expression of apoptosis-related genes. Both concentration of the transcriptional repertoire on pre-BCR-related genes together with marked up-regulation of apoptosis mediators in PBC might reflect selection for the expression of a functional pre-BCR within the bone marrow. Besides known regulator genes of early B cell development such as PAX5, E2A, and EBF, the most abundantly expressed genes in PBCs include ATM, PDGFRA, SIAH1, PIM2, C/EBPB, WNT16, and TCL1, the role of which has not been established yet in early B cell development.
Müschen
Markus
M
Institute for Genetics, University of Cologne, Weyertal 121, 50931 Cologne, Germany. markus.mueschen@uni-koeln.de
Lee
Sanggyu
S
Zhou
Guolin
G
Feldhahn
Niklas
N
Barath
Varun Singh
VS
Chen
Jianjun
J
Moers
Cordula
C
Krönke
Martin
M
Rowley
Janet D
JD
Wang
San Ming
SM
D015703:Antigens, CD / Q000032:analysis*; D018941:Antigens, CD19 / Q000032:analysis; D018952:Antigens, CD34 / Q000032:analysis; D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000502:physiology; D001402:B-Lymphocytes / Q000145:classification / Q000166:cytology / Q000502:physiology*; D002454:Cell Differentiation; D005786:Gene Expression Regulation; D015723:Gene Library; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000502:physiology*; D006801:Humans; D016130:Immunophenotyping; D015260:Neprilysin / Q000032:analysis; D012333:RNA, Messenger / Q000235:genetics; D014158:Transcription, Genetic
D015703:Antigens, CD; D018941:Antigens, CD19; D018952:Antigens, CD34; D012333:RNA, Messenger; D015260:Neprilysin