Unveiling the complexity of transcription factor networks in hematopoietic stem cells: implications for cell therapy and hematological malignancies
The functionality and longevity of hematopoietic tissue is ensured by a tightly controlled balance between self-renewal, quiescence, and differentiation of hematopoietic stem cells (HSCs) into the many different blood lineages. Cell fate determination in HSCs is influenced by signals from extrinsic...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-06-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2023.1151343/full |
| _version_ | 1797794347718017024 |
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| author | Aissa Benyoucef Aissa Benyoucef Jody J. Haigh Jody J. Haigh Marjorie Brand Marjorie Brand |
| author_facet | Aissa Benyoucef Aissa Benyoucef Jody J. Haigh Jody J. Haigh Marjorie Brand Marjorie Brand |
| author_sort | Aissa Benyoucef |
| collection | DOAJ |
| description | The functionality and longevity of hematopoietic tissue is ensured by a tightly controlled balance between self-renewal, quiescence, and differentiation of hematopoietic stem cells (HSCs) into the many different blood lineages. Cell fate determination in HSCs is influenced by signals from extrinsic factors (e.g., cytokines, irradiation, reactive oxygen species, O2 concentration) that are translated and integrated by intrinsic factors such as Transcription Factors (TFs) to establish specific gene regulatory programs. TFs also play a central role in the establishment and/or maintenance of hematological malignancies, highlighting the need to understand their functions in multiple contexts. TFs bind to specific DNA sequences and interact with each other to form transcriptional complexes that directly or indirectly control the expression of multiple genes. Over the past decades, significant research efforts have unraveled molecular programs that control HSC function. This, in turn, led to the identification of more than 50 TF proteins that influence HSC fate. However, much remains to be learned about how these proteins interact to form molecular networks in combination with cofactors (e.g. epigenetics factors) and how they control differentiation, expansion, and maintenance of cellular identity. Understanding these processes is critical for future applications particularly in the field of cell therapy, as this would allow for manipulation of cell fate and induction of expansion, differentiation, or reprogramming of HSCs using specific cocktails of TFs. Here, we review recent findings that have unraveled the complexity of molecular networks controlled by TFs in HSCs and point towards possible applications to obtain functional HSCs ex vivo for therapeutic purposes including hematological malignancies. Furthermore, we discuss the challenges and prospects for the derivation and expansion of functional adult HSCs in the near future. |
| first_indexed | 2024-03-13T03:00:25Z |
| format | Article |
| id | doaj.art-477ed87a6d6840a582a3aed0f8aa038c |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-03-13T03:00:25Z |
| publishDate | 2023-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-477ed87a6d6840a582a3aed0f8aa038c2023-06-27T13:11:48ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2023-06-011310.3389/fonc.2023.11513431151343Unveiling the complexity of transcription factor networks in hematopoietic stem cells: implications for cell therapy and hematological malignanciesAissa Benyoucef0Aissa Benyoucef1Jody J. Haigh2Jody J. Haigh3Marjorie Brand4Marjorie Brand5Department of Pharmacology and Therapeutics, Rady Faulty of Health Sciences, University of Manitoba, Winnipeg, MB, CanadaCancerCare Manitoba Research Institute, Winnipeg, MB, CanadaDepartment of Pharmacology and Therapeutics, Rady Faulty of Health Sciences, University of Manitoba, Winnipeg, MB, CanadaCancerCare Manitoba Research Institute, Winnipeg, MB, CanadaSprott Center for Stem Cell Research, Ottawa Hospital Research Institute, Ottawa, ON, CanadaDepartment of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON, CanadaThe functionality and longevity of hematopoietic tissue is ensured by a tightly controlled balance between self-renewal, quiescence, and differentiation of hematopoietic stem cells (HSCs) into the many different blood lineages. Cell fate determination in HSCs is influenced by signals from extrinsic factors (e.g., cytokines, irradiation, reactive oxygen species, O2 concentration) that are translated and integrated by intrinsic factors such as Transcription Factors (TFs) to establish specific gene regulatory programs. TFs also play a central role in the establishment and/or maintenance of hematological malignancies, highlighting the need to understand their functions in multiple contexts. TFs bind to specific DNA sequences and interact with each other to form transcriptional complexes that directly or indirectly control the expression of multiple genes. Over the past decades, significant research efforts have unraveled molecular programs that control HSC function. This, in turn, led to the identification of more than 50 TF proteins that influence HSC fate. However, much remains to be learned about how these proteins interact to form molecular networks in combination with cofactors (e.g. epigenetics factors) and how they control differentiation, expansion, and maintenance of cellular identity. Understanding these processes is critical for future applications particularly in the field of cell therapy, as this would allow for manipulation of cell fate and induction of expansion, differentiation, or reprogramming of HSCs using specific cocktails of TFs. Here, we review recent findings that have unraveled the complexity of molecular networks controlled by TFs in HSCs and point towards possible applications to obtain functional HSCs ex vivo for therapeutic purposes including hematological malignancies. Furthermore, we discuss the challenges and prospects for the derivation and expansion of functional adult HSCs in the near future.https://www.frontiersin.org/articles/10.3389/fonc.2023.1151343/fullhematopoietic stem cellstranscription factorreprogrammingcell therapy and hematological malignanciestrans-differentiation |
| spellingShingle | Aissa Benyoucef Aissa Benyoucef Jody J. Haigh Jody J. Haigh Marjorie Brand Marjorie Brand Unveiling the complexity of transcription factor networks in hematopoietic stem cells: implications for cell therapy and hematological malignancies Frontiers in Oncology hematopoietic stem cells transcription factor reprogramming cell therapy and hematological malignancies trans-differentiation |
| title | Unveiling the complexity of transcription factor networks in hematopoietic stem cells: implications for cell therapy and hematological malignancies |
| title_full | Unveiling the complexity of transcription factor networks in hematopoietic stem cells: implications for cell therapy and hematological malignancies |
| title_fullStr | Unveiling the complexity of transcription factor networks in hematopoietic stem cells: implications for cell therapy and hematological malignancies |
| title_full_unstemmed | Unveiling the complexity of transcription factor networks in hematopoietic stem cells: implications for cell therapy and hematological malignancies |
| title_short | Unveiling the complexity of transcription factor networks in hematopoietic stem cells: implications for cell therapy and hematological malignancies |
| title_sort | unveiling the complexity of transcription factor networks in hematopoietic stem cells implications for cell therapy and hematological malignancies |
| topic | hematopoietic stem cells transcription factor reprogramming cell therapy and hematological malignancies trans-differentiation |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2023.1151343/full |
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