Fetal hepatic progenitors support long-term expansion of hematopoietic stem cells
We have developed a coculture system that establishes DLK[superscript +] fetal hepatic progenitors as the authentic supportive cells for expansion of hematopoietic stem (HSCs) and progenitor cells. In 1-week cultures supplemented with serum and supportive cytokines, both cocultured DLK[superscript +...
| Main Authors: | , , |
|---|---|
| Other Authors: | |
| Format: | Article |
| Language: | en_US |
| Published: |
Elsevier
2016
|
| Online Access: | http://hdl.handle.net/1721.1/102178 https://orcid.org/0000-0002-7029-7415 |
| _version_ | 1811074574453833728 |
|---|---|
| author | Chou, Song Flygare, Johan Lodish, Harvey F |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Chou, Song Flygare, Johan Lodish, Harvey F |
| author_sort | Chou, Song |
| collection | MIT |
| description | We have developed a coculture system that establishes DLK[superscript +] fetal hepatic progenitors as the authentic supportive cells for expansion of hematopoietic stem (HSCs) and progenitor cells. In 1-week cultures supplemented with serum and supportive cytokines, both cocultured DLK[superscript +] fetal hepatic progenitors and their conditioned medium supported rapid expansion of hematopoietic progenitors and a small increase in HSC numbers. In 2- and 3-week cultures DLK[superscript +] cells, but not their conditioned medium, continuously and significantly (>20-fold) expanded both hematopoietic stem and progenitor cells. Physical contact between HSCs and DLK[superscript +] cells was crucial to maintaining this long-term expansion. Similar HSC expansion (approximately sevenfold) was achieved in cocultures using a serum-free, low cytokine- containing medium. In contrast, DLK[superscript -] cells are incapable of expanding hematopoietic cells, demonstrating that hepatic progenitors are the principle supportive cells for HSC expansion in the fetal liver. |
| first_indexed | 2024-09-23T09:51:58Z |
| format | Article |
| id | mit-1721.1/102178 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T09:51:58Z |
| publishDate | 2016 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | mit-1721.1/1021782022-09-30T17:21:35Z Fetal hepatic progenitors support long-term expansion of hematopoietic stem cells Chou, Song Flygare, Johan Lodish, Harvey F Massachusetts Institute of Technology. Department of Biology Whitehead Institute for Biomedical Research Lodish, Harvey F. We have developed a coculture system that establishes DLK[superscript +] fetal hepatic progenitors as the authentic supportive cells for expansion of hematopoietic stem (HSCs) and progenitor cells. In 1-week cultures supplemented with serum and supportive cytokines, both cocultured DLK[superscript +] fetal hepatic progenitors and their conditioned medium supported rapid expansion of hematopoietic progenitors and a small increase in HSC numbers. In 2- and 3-week cultures DLK[superscript +] cells, but not their conditioned medium, continuously and significantly (>20-fold) expanded both hematopoietic stem and progenitor cells. Physical contact between HSCs and DLK[superscript +] cells was crucial to maintaining this long-term expansion. Similar HSC expansion (approximately sevenfold) was achieved in cocultures using a serum-free, low cytokine- containing medium. In contrast, DLK[superscript -] cells are incapable of expanding hematopoietic cells, demonstrating that hepatic progenitors are the principle supportive cells for HSC expansion in the fetal liver. National Institutes of Health (U.S.) (Grant P01 HL 32262) National Institutes of Health (U.S.) (Grant DK067356) 2016-04-06T15:52:14Z 2016-04-06T15:52:14Z 2013-02 2013-01 Article http://purl.org/eprint/type/JournalArticle 0301472X http://hdl.handle.net/1721.1/102178 Chou, Song, Johan Flygare, and Harvey F. Lodish. “Fetal Hepatic Progenitors Support Long-Term Expansion of Hematopoietic Stem Cells.” Experimental Hematology 41, no. 5 (May 2013): 479–490.e4. https://orcid.org/0000-0002-7029-7415 en_US http://dx.doi.org/10.1016/j.exphem.2013.02.003 Experimental Hematology Creative Commons Attribution-Noncommercial-NoDerivatives http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Elsevier PMC |
| spellingShingle | Chou, Song Flygare, Johan Lodish, Harvey F Fetal hepatic progenitors support long-term expansion of hematopoietic stem cells |
| title | Fetal hepatic progenitors support long-term expansion of hematopoietic stem cells |
| title_full | Fetal hepatic progenitors support long-term expansion of hematopoietic stem cells |
| title_fullStr | Fetal hepatic progenitors support long-term expansion of hematopoietic stem cells |
| title_full_unstemmed | Fetal hepatic progenitors support long-term expansion of hematopoietic stem cells |
| title_short | Fetal hepatic progenitors support long-term expansion of hematopoietic stem cells |
| title_sort | fetal hepatic progenitors support long term expansion of hematopoietic stem cells |
| url | http://hdl.handle.net/1721.1/102178 https://orcid.org/0000-0002-7029-7415 |
| work_keys_str_mv | AT chousong fetalhepaticprogenitorssupportlongtermexpansionofhematopoieticstemcells AT flygarejohan fetalhepaticprogenitorssupportlongtermexpansionofhematopoieticstemcells AT lodishharveyf fetalhepaticprogenitorssupportlongtermexpansionofhematopoieticstemcells |