Molecular portraits of B cell lineage commitment

Markus Müschen, Sanggyu Lee, Guolin Zhou, Niklas Feldhahn, Varun Singh Barath, Jianjun Chen, Cordula Moers, Martin Krönke, Janet D. Rowley, San Ming Wang

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)10014-10019
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume99
Issue number15
DOIs
Publication statusPublished - Jul 23 2002

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Müschen, M., Lee, S., Zhou, G., Feldhahn, N., Barath, V. S., Chen, J., ... Wang, S. M. (2002). Molecular portraits of B cell lineage commitment. Proceedings of the National Academy of Sciences of the United States of America, 99(15), 10014-10019. https://doi.org/10.1073/pnas.152327399