Clonal analysis via barcoding reveals diverse growth and differentiation of transplanted mouse and human mammary stem cells.
Cellular barcoding offers a powerful approach to characterize the growth and differentiation activity of large numbers of cotransplanted stem cells. Here, we describe a lentiviral genomic-barcoding and analysis strategy and its use to compare the clonal outputs of transplants of purified mouse and human basal mammary epithelial cells. We found that both sources of transplanted cells produced many bilineage mammary epithelial clones in primary recipients, although primary clones containing only one detectable mammary lineage were also common. Interestingly, regardless of the species of origin, many clones evident in secondary recipients were not detected in the primary hosts, and others that were changed from appearing luminal-restricted to appearing bilineage. This barcoding methodology has thus revealed conservation between mice and humans of a previously unknown diversity in the growth and differentiation activities of their basal mammary epithelial cells stimulated to grow in transplanted hosts.
Terry Fox Laboratory, BC Cancer Agency, 675 West 10(th) Avenue, Vancouver, BC V5Z 1L3, Canada.
Long V
LV
Nguyen
Terry Fox Laboratory, BC Cancer Agency, 675 West 10(th) Avenue, Vancouver, BC V5Z 1L3, Canada.
Maisam
M
Makarem
Department of Microbiology and Immunology, Centre for High-Throughput Biology, University of British Columbia, 2125 East Mall, Vancouver, BC V6T 1Z4, Canada.
Annaick
A
Carles
Department of Microbiology and Immunology, Centre for High-Throughput Biology, University of British Columbia, 2125 East Mall, Vancouver, BC V6T 1Z4, Canada.
Michelle
M
Moksa
Terry Fox Laboratory, BC Cancer Agency, 675 West 10(th) Avenue, Vancouver, BC V5Z 1L3, Canada.
Nagarajan
N
Kannan
Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, 675 West 10(th) Avenue, Vancouver, BC V5Z 1L3, Canada.
Pawan
P
Pandoh
Department of Molecular Oncology, BC Cancer Agency, 675 West 10(th) Avenue, Vancouver, BC V5Z 1L3, Canada.
Peter
P
Eirew
Department of Molecular Oncology, BC Cancer Agency, 675 West 10(th) Avenue, Vancouver, BC V5Z 1L3, Canada.
Tomo
T
Osako
Terry Fox Laboratory, BC Cancer Agency, 675 West 10(th) Avenue, Vancouver, BC V5Z 1L3, Canada.
Melanie
M
Kardel
La Ka Shing Faculty of Medicine, University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong.
Alice M S
AM
Cheung
Terry Fox Laboratory, BC Cancer Agency, 675 West 10(th) Avenue, Vancouver, BC V5Z 1L3, Canada.
William
W
Kennedy
Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, 675 West 10(th) Avenue, Vancouver, BC V5Z 1L3, Canada.
Kane
K
Tse
Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, 675 West 10(th) Avenue, Vancouver, BC V5Z 1L3, Canada.
Thomas
T
Zeng
Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, 675 West 10(th) Avenue, Vancouver, BC V5Z 1L3, Canada.
Yongjun
Y
Zhao
Terry Fox Laboratory, BC Cancer Agency, 675 West 10(th) Avenue, Vancouver, BC V5Z 1L3, Canada.
R Keith
RK
Humphries
Department of Molecular Oncology, BC Cancer Agency, 675 West 10(th) Avenue, Vancouver, BC V5Z 1L3, Canada; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC V6T 2B5, Canada.
Samuel
S
Aparicio
Terry Fox Laboratory, BC Cancer Agency, 675 West 10(th) Avenue, Vancouver, BC V5Z 1L3, Canada. Electronic address: ceaves@bccrc.ca.
Connie J
CJ
Eaves
Department of Microbiology and Immunology, Centre for High-Throughput Biology, University of British Columbia, 2125 East Mall, Vancouver, BC V6T 1Z4, Canada; Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, 675 West 10(th) Avenue, Vancouver, BC V5Z 1L3, Canada. Electronic address: mhirst@bcgsc.ca.
Martin
M
Hirst
D000818:Animals; D018929:Cell Culture Techniques / Q000379:methods*; D002454:Cell Differentiation; D019070:Cell Lineage; D049109:Cell Proliferation; D048429:Cell Size; D002999:Clone Cells; D004847:Epithelial Cells / Q000166:cytology / Q000637:transplantation; D005260:Female; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008321:Mammary Glands, Animal / Q000166:cytology*; D042361:Mammary Glands, Human / Q000166:cytology*; D051379:Mice; D012038:Regeneration; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology*