BCL11B Drives Human Mammary Stem Cell Self-Renewal In Vitro by Inhibiting Basal Differentiation
The epithelial compartment of the mammary gland contains basal and luminal cell lineages, as well as stem and progenitor cells that reside upstream in the differentiation hierarchy. Stem and progenitor cell differentiation is regulated to maintain adult tissue and mediate expansion during pregnancy...
| Main Authors: | , , , , , , , |
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Elsevier
2018
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| Online Access: | http://hdl.handle.net/1721.1/116579 https://orcid.org/0000-0002-4866-1145 https://orcid.org/0000-0003-1533-6730 https://orcid.org/0000-0002-2988-0537 https://orcid.org/0000-0002-9703-1780 |
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| author | Cabrera, Janel R. Gorelov, Rebecca A. Kuperwasser, Charlotte Miller, Daniel Handel Jin, Dexter X. Sokol, Ethan Samuel Superville, Daphne A. Gupta, Piyush |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Cabrera, Janel R. Gorelov, Rebecca A. Kuperwasser, Charlotte Miller, Daniel Handel Jin, Dexter X. Sokol, Ethan Samuel Superville, Daphne A. Gupta, Piyush |
| author_sort | Cabrera, Janel R. |
| collection | MIT |
| description | The epithelial compartment of the mammary gland contains basal and luminal cell lineages, as well as stem and progenitor cells that reside upstream in the differentiation hierarchy. Stem and progenitor cell differentiation is regulated to maintain adult tissue and mediate expansion during pregnancy and lactation. The genetic factors that regulate the transition of cells between differentiation states remain incompletely understood. Here, we present a genome-scale method to discover genes driving cell-state specification. Applying this method, we identify a transcription factor, BCL11B, which drives stem cell self-renewal in vitro, by inhibiting differentiation into the basal lineage. To validate BCL11B's functional role, we use two-dimensional colony-forming and three-dimensional tissue differentiation assays to assess the lineage differentiation potential and functional abilities of primary human mammary cells. These findings show that BCL11B regulates mammary cell differentiation and demonstrate the utility of our proposed genome-scale strategy for identifying lineage regulators in mammalian tissues. Miller et al. describe a strategy to identify candidate master regulators of cell lineage specification. This approach identified BCL11B as a key regulator of human mammary stem cell self-renewal in in vitro progenitor and differentiation assays. Using a combination of 2D and 3D primary cell culture techniques, they show that BCL11B drives stem cell self-renewal by inhibiting basal lineage commitment. |
| first_indexed | 2024-09-23T10:29:14Z |
| format | Article |
| id | mit-1721.1/116579 |
| institution | Massachusetts Institute of Technology |
| last_indexed | 2024-09-23T10:29:14Z |
| publishDate | 2018 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | mit-1721.1/1165792022-09-30T21:28:24Z BCL11B Drives Human Mammary Stem Cell Self-Renewal In Vitro by Inhibiting Basal Differentiation Cabrera, Janel R. Gorelov, Rebecca A. Kuperwasser, Charlotte Miller, Daniel Handel Jin, Dexter X. Sokol, Ethan Samuel Superville, Daphne A. Gupta, Piyush Massachusetts Institute of Technology. Department of Biology Koch Institute for Integrative Cancer Research at MIT Miller, Daniel Handel Jin, Dexter X. Sokol, Ethan Samuel Superville, Daphne A. Gupta, Piyush The epithelial compartment of the mammary gland contains basal and luminal cell lineages, as well as stem and progenitor cells that reside upstream in the differentiation hierarchy. Stem and progenitor cell differentiation is regulated to maintain adult tissue and mediate expansion during pregnancy and lactation. The genetic factors that regulate the transition of cells between differentiation states remain incompletely understood. Here, we present a genome-scale method to discover genes driving cell-state specification. Applying this method, we identify a transcription factor, BCL11B, which drives stem cell self-renewal in vitro, by inhibiting differentiation into the basal lineage. To validate BCL11B's functional role, we use two-dimensional colony-forming and three-dimensional tissue differentiation assays to assess the lineage differentiation potential and functional abilities of primary human mammary cells. These findings show that BCL11B regulates mammary cell differentiation and demonstrate the utility of our proposed genome-scale strategy for identifying lineage regulators in mammalian tissues. Miller et al. describe a strategy to identify candidate master regulators of cell lineage specification. This approach identified BCL11B as a key regulator of human mammary stem cell self-renewal in in vitro progenitor and differentiation assays. Using a combination of 2D and 3D primary cell culture techniques, they show that BCL11B drives stem cell self-renewal by inhibiting basal lineage commitment. National Science Foundation (U.S.) (Grant 1122374) 2018-06-25T18:46:29Z 2018-06-25T18:46:29Z 2018-03 2018-01 2018-06-21T13:57:13Z Article http://purl.org/eprint/type/JournalArticle 2213-6711 http://hdl.handle.net/1721.1/116579 Miller, Daniel H. et al. “BCL11B Drives Human Mammary Stem Cell Self-Renewal In Vitro by Inhibiting Basal Differentiation.” Stem Cell Reports 10, 3 (March 2018): 1131–1145 © 2018 The Authors https://orcid.org/0000-0002-4866-1145 https://orcid.org/0000-0003-1533-6730 https://orcid.org/0000-0002-2988-0537 https://orcid.org/0000-0002-9703-1780 http://dx.doi.org/10.1016/j.stemcr.2018.01.036 Stem Cell Reports Creative Commons Attribution-NonCommercial-NoDerivs License http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Elsevier Elsevier |
| spellingShingle | Cabrera, Janel R. Gorelov, Rebecca A. Kuperwasser, Charlotte Miller, Daniel Handel Jin, Dexter X. Sokol, Ethan Samuel Superville, Daphne A. Gupta, Piyush BCL11B Drives Human Mammary Stem Cell Self-Renewal In Vitro by Inhibiting Basal Differentiation |
| title | BCL11B Drives Human Mammary Stem Cell Self-Renewal In Vitro by Inhibiting Basal Differentiation |
| title_full | BCL11B Drives Human Mammary Stem Cell Self-Renewal In Vitro by Inhibiting Basal Differentiation |
| title_fullStr | BCL11B Drives Human Mammary Stem Cell Self-Renewal In Vitro by Inhibiting Basal Differentiation |
| title_full_unstemmed | BCL11B Drives Human Mammary Stem Cell Self-Renewal In Vitro by Inhibiting Basal Differentiation |
| title_short | BCL11B Drives Human Mammary Stem Cell Self-Renewal In Vitro by Inhibiting Basal Differentiation |
| title_sort | bcl11b drives human mammary stem cell self renewal in vitro by inhibiting basal differentiation |
| url | http://hdl.handle.net/1721.1/116579 https://orcid.org/0000-0002-4866-1145 https://orcid.org/0000-0003-1533-6730 https://orcid.org/0000-0002-2988-0537 https://orcid.org/0000-0002-9703-1780 |
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