Supplemental tables and figures "An RNAi-based screening of clinically relevant transcription factors regulating human adipogenesis and adipocyte metabolism"

These are supplemental tables and figures to the study ""An RNAi-based phenotypic screening of clinically relevant transcription factors regulating human adipogenesis and adipocyte metabolism"The abstract:

Objective Healthy hyperplasic (many but smaller fat cells)
white adipose tissue (WAT) expansion is mediated
by recruitment, proliferation and/or differentiation of new fat cells. This
process (adipogenesis) is controlled by transcriptional programs mostly
identified in rodents. A
systemic investigation of adipogenic human transcription factors (TFs) that are
relevant for metabolic conditions has not been revealed previously.

Methods TFs
regulated in WAT by obesity, adipose morphology, cancer cachexia and insulin
resistance were selected from microarrays. Their role in differentiation of human
adipose tissue-derived stem cells (hASC) was investigated by RNA interference
(RNAi) screen. Lipid accumulation, cell number and lipolysis were measured for
all screened factors (148 TFs). RNA (RNAseq), protein (western blot) expression,
insulin and catecholamine responsiveness were examined in hASC following siRNA
treatment of selected target TFs.

Results Analysis
of TFs regulated by metabolic conditions in human WAT revealed that many of
them belong to adipogenesis-regulating pathways. The RNAi screen identified 39
genes that affected fat cell differentiation in vitro, where 11 genes were novel. Of the latter JARID2 stood out
as being necessary for formation of healthy fat cell metabolic phenotype by regulating
expression of multiple fat-cell phenotype-specific genes.

Conclusions This
comprehensive RNAi screening in hASC suggests that a large proportion of WAT TFs
that are impacted by metabolic conditions might be important for hyperplastic adipose
tissue expansion. The screen also identified JARID2 as a novel TF essential for
the development of functional adipocytes.

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