Stem cell antigen 2: a new gene involved in the self-renewal of erythroid progenitors.
OBJECTIVE
Stem cell antigen 2 (SCA2), also known as TSA1 and LY6E, is a glycosylphosphatidylinositol-anchored molecule that belongs to the Ly-6 family and whose function remains largely unknown. We have previously shown that SCA2 is overexpressed in self-renewing avian erythroid progenitors (T2ECs) as opposed to differentiating T2ECs. The aim of this study was to define the role of SCA2 in the switch between self-renewal and differentiation of erythroid progenitors.


METHODS
We have investigated the cellular processes controlled by SCA2 in T2ECs by RNA interference and overexpression approaches. Moreover, we have used a SAGE Querying and analysis tools developed in our laboratory, to investigate the expression level of SCA2 gene in different human cell types.


RESULTS
We demonstrate the regulation of SCA2 expression by TGF-beta, a growth factor essential for self-renewal of T2ECs. We establish that SCA2 knockdown by RNA interference reduced the proliferation and promoted the differentiation of T2ECs. In contrast, SCA2 overexpression inhibited differentiation of T2ECs only. Furthermore, by using a bioinformatic approach, we found that SCA2 is highly expressed in a variety of human cancer cells. We confirmed this result by quantitative PCR on human colon and kidney tissues.


CONCLUSIONS
Altogether, these findings imply that SCA2 may function in a dose-dependent manner to support the self-renewal state and that its deregulation might contribute to the development of some human cancers.
Bresson-Mazet
C
C
Université de Lyon, Lyon, France.
Gandrillon
O
O
Gonin-Giraud
S
S
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002645:Chickens; D015536:Down-Regulation / Q000187:drug effects; D015672:Erythroid Precursor Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D009369:Neoplasms / Q000235:genetics; D034622:RNA Interference; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000494:pharmacology
D008565:Membrane Proteins; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; C084839:thymic shared antigen-1