Cells isolated from the epidermis by Hoechst dye exclusion, small size, and negative selection for hematopoietic markers can generate B lymphocyte precursors.
Transdifferentiation has become a common claim for somatic stem cells, yet how such cells can be directed toward a specified cell lineage has not been well investigated. We previously demonstrated that when isolated epidermal stem cells were placed into an embryonic environment, their potential was extended beyond the keratinocyte lineage. Here, we present evidence that cells isolated using a modification of our published method for epidermal stem cells can be specifically directed to differentiate into B lymphocyte precursors. We found that these isolated cells co-cultured with S17 bone marrow stromal cells in cytokine-supplemented medium changed their cell surface marker profile and gene expression pattern to one characteristic of B lymphocyte precursors. Such cells also underwent variable, diversity, joining rearrangement at the immunoglobulin heavy-chain locus, a permanent genetic change unique to lymphocytes. This feature is limited to the cells isolated using the modified epidermal stem cell method, as cells isolated using the modified transit amplifying cell method could not be re-directed or reprogrammed. Such results demonstrate that cells from the epidermis can be directed to cross lineage boundaries to become mesodermally derived lymphocytes.
Stern
Mathew M
MM
Department of Anatomy and Cell Biology, The University of Iowa Carver College of Medicine, Iowa City, Iowa 52242, USA.
Tygrett
Lorraine T
LT
Waldschmidt
Thomas J
TJ
Bickenbach
Jackie R
JR
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology* / Q000378:metabolism; D001562:Benzimidazoles / Q000494:pharmacology*; D001854:Bone Marrow Cells / Q000166:cytology; D002454:Cell Differentiation; D003584:Cytological Techniques; D000078404:Epidermal Cells; D004817:Epidermis / Q000473:pathology*; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism; D006413:Hematopoietic System; D007143:Immunoglobulin Heavy Chains / Q000737:chemistry; D008214:Lymphocytes / Q000166:cytology; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D017154:Stromal Cells / Q000166:cytology
D001562:Benzimidazoles; D007143:Immunoglobulin Heavy Chains; C017807:bisbenzimide ethoxide trihydrochloride