Examples for 3′ A additions (A), U additions (B), and A to G nucleotide exchanges due to possible deamination events (C) are given. Nucleotides of sequenced miRNAs that do not match their genomic sequence are colored. The black bar underneath each sequence logo indicates the predominantly cloned sequence. A list of all modifications and their occurrence in the different libraries is given in Tables S24 and S25.

miRNA precursor clusters with at least 5% relative cloning frequency in at least one of the samples are depicted individually in a color code. All other miRNAs and viral miRNAs were pooled and are displayed together. Undetected miRNAs are displayed in black. Hematopoietic-specific miRNA clusters are marked by black dots. B-, T- and dendritic cell (DC) samples were combined and their composite profiles are shown in panel (A) while panel B, C, and D, respectively, show the individual samples. The lineage is indicated above each figure. Different disease entities and normal cells are indicated with color bars. Patient-derived samples are labeled with the disease name and patient number, while for cell lines the respective names are given. The FAB classification is given for the AML samples and the progenitor cells are indicated. Abbreviations: LMPP, lymphoid primed multipotent progenitor; CLP, common lymphoid progenitor; CMP, common myeloid progenitor; GMP, granulocyte/macrophage progenitor; MkEP, megakaryocyte/erythrocyte progenitor; BM remission, bone marrow in remission; DLBCL, diffuse large B-cell lymphoma; MZ, marginal zone; MC, mantle cell; FL, follicular lymphoma; BL, Burkitt’s lymphoma; PC, plasmocytoma; HL, Hodgkin lymphoma.

Cell lines were treated and differentiated into neurons (A) and osteoblasts (B). (C) A thyroid stimulating hormone (TSH)-dependent rat cell line FRTL5 was dedifferentiated by induction of a chimeric RAS protein. Expression profiles for orthologous miRNA precursor clusters with 5% or more relative cloning frequency in at least one sample are depicted in a color-coded manner (see Figure 3 for details). Abbreviations: dcAMP, dibutyryl cAMP; FBS, fetal bovine serum; TPA, trans-phorbol ester; RA, retinoic acid; USSC, human unrestricted somatic stem cell; orth, indicates that the hsa-mir-470 cluster is orthologous to the rodent mir-463 clusters.

(A) The 51 most specific miRNA precursor clusters for human and mouse are depicted. The total height of each bar represents the information content reflecting tissue specificity, while the relative heights for each of the tissues are proportional to the clones of a miRNA precursor cluster in a given tissue type relative to all tissue types. The enrichment of miR-124 in the endocrine tissue in mouse is due to high expression of this miRNA in the MIN-6 beta-cell line, but miR-124 is not expressed in primary β-cells residing in mouse or human islets. (B) The 26 most expressed miRNA precursor clusters for human and mouse are depicted. The mean clone count for each tissue type (striped bars) and the tissue specificity (white bars) are indicated. The most abundant miRNA clusters are ubiquitously expressed and show little tissue specificity.

Expression profiles of miRNA precursor clusters with at least 5% relative expression in one of the samples as well as the neuronal-specific miRNA clusters (marked with black dot) are depicted individually for human (A), mouse (B) and rat (C) brain sections, brain tumor samples (FC0020688, WL210995, DD040800) and cell lines as indicated (color code of expression values see Figure 3). The open circles indicate miRNAs enriched in endocrine tissue including the pituitary gland. All panels show orthologous miRNA precursor clusters (if present). Abbreviations: dcAMP, dibutyryl cAMP; FBS, fetal bovine serum; TPA, trans-phorbol ester; RA, retinoic acid; orth, indicates that the hsa-mir-470 cluster is orthologous to the rodent mir-463 clusters.